interleukin-8 and Diabetes-Mellitus--Type-2

Diabetic nephropathy is a multifactorial disease. Gene susceptibility, as well as environmental exposure, plays an important role in disease progression. Malaysia is reported to be among the world's second-fastest-growing rates of kidney failure. Diabetic nephropathy has become the main cause of end-stage renal disease in Malaysia. This article is aimed at reviewing genetic studies conducted among diabetic nephropathy patients in the Malaysian population. This review was conducted by searching PubMed, MEDLINE, and Google Scholar databases to identify all relevant papers published in English from March 2022 to April 2022, using the following keywords: diabetes, type 2 diabetes, diabetic nephropathy, diabetic kidney disease, and Malaysia. The case-control study among diabetic patients with and without diabetic nephropathy showed a significant association with diabetic nephropathy in CNDP1, NOS3, and MnSOD genes. In the ethnic subgroup analysis, significant differences for diabetic nephropathy in terms of diabetes duration (≥10 years) were observed for CCL2 rs3917887, CCR5 rs1799987, ELMO1 rs74130, and IL8 rs4073. The IL8 rs4073 was associated only with the Indians, while the CCR5 rs1799987 was associated with the Chinese. In Malays, SLC12A3 Arg913Gln polymorphism and ICAM1 K469E (A/G) polymorphism were found to be associated with diabetic nephropathy. Studies on gene-environment interactions have suggested significant genetic and environmental factors such as smoking, waist circumference, and sex for eNOS rs2070744, PPARGC1A rs8192678, KCNQ1 rs2237895, and KCNQ1 rs2283228 with kidney disease. The genetic variants' contributions differed across ethnic groups. Therefore, a study to validate the genetic variants that are found to be associated with different ethnicities in Malaysia may be important in future studies.

Topics: Case-Control Studies; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Epigenesis, Genetic; Genetic Predisposition to Disease; Humans; Interleukin-8; KCNQ1 Potassium Channel; Malaysia; Polymorphism, Single Nucleotide; Solute Carrier Family 12, Member 3

Obesity, type 2 diabetes (T2DM), hypertension (HTN), and Cardiovascular Disease (CVD) often cluster together as "Cardiometabolic Disease" (CMD). Just under 50% of patients with CMD increased the risk of morbidity and mortality right from the beginning of the COVID-19 pandemic as it has been reported in most countries affected by the SARS-CoV2 virus. One of the pathophysiological hallmarks of COVID-19 is the overactivation of the immune system with a prominent IL-6 response, resulting in severe and systemic damage involving also cytokines such as IL2, IL4, IL8, IL10, and interferon-gamma were considered strong predictors of COVID-19 severity. Thus, in this mini-review, we try to describe the inflammatory state, the alteration of the adipokine profile, and cytokine production in the obese state of infected and not infected patients by SARS-CoV2 with the final aim to find possible influences of COVID-19 on CMD and CVD. The immunological-based discussion of the molecular processes could inspire the study of promising targets for managing CMD patients and its complications during COVID-19.

Topics: Adipokines; Cardiovascular Diseases; COVID-19; Cytokines; Diabetes Mellitus, Type 2; Humans; Interferon-gamma; Interleukin-10; Interleukin-2; Interleukin-4; Interleukin-6; Interleukin-8; Obesity; Pandemics; RNA, Viral; SARS-CoV-2

PurposeThe aim of the present study is to investigate the association of the polymorphism of two genes in CXC chemokine family, interleukin-8 (IL-8) and interferon-inducible protein 10 (IP-10), with both susceptibility and progression of DR in T2D population of northern China.Patients and methodsA total of 1043 eligible type 2 diabetic patients from Heilongjiang of northern China were recruited for this study. They were grouped into: with diabetic retinopathy (DR, 528 cases) and without diabetic retinopathy (DNR, 515 cases). Single nucleotide polymorphism (SNP) genotyping of IL-8(-251T/A) and IP-10(-1596C/T) was performed by polymerase chain reaction. Multivariate analysis and stepwise multiple logistic progression analysis were conducted to evaluate the association between gene SNP and DR susceptibility and progression. Pooled odds ratio (OR) with 95% confidence interval (CI) was applied to assess the strength of the association among study groups.ResultsThe occurring of IL-8(-251) AA genotype was correlated with susceptibility (OR: 2.286, 95% CI: 1.382-3.782, P=0.001) and progression of high-risk proliferative diabetic retinopathy (PDR) (OR: 0.354, 95% CI: 0.162-0.770, P=0.009). Reversely, T allele of IP-10 (-1596) C/T was correlated with a reduced risk of DR (OR: 0.341, 95% CI: 0.249-0.466, P<0.001). However, gene polymorphisms of IL-8-251T/A and IP-10-1596C/T were not associated with diabetic macular edema (DME)(P>0.05).ConclusionsAA genotype of IL-8-251T/A was closely correlated to DR and high-risk proliferative diabetic retinopathy (PDR). -1596T allele of the IP-10 is a beneficial genotype for DR.

Topics: Adult; Aged; Aged, 80 and over; Asian People; Case-Control Studies; Chemokine CXCL10; China; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Disease Progression; Female; Genetic Predisposition to Disease; Genotype; Humans; Interleukin-8; Male; Middle Aged; Polymorphism, Single Nucleotide

Middle East Respiratory Syndrome (MERS) is a novel respiratory illness firstly reported in Saudi Arabia in 2012. It is caused by a new corona virus, called MERS corona virus (MERS-CoV). Most people who have MERS-CoV infection developed severe acute respiratory illness.. This work is done to determine the clinical characteristics and the outcome of intensive care unit (ICU) admitted patients with confirmed MERS-CoV infection.. This study included 32 laboratory confirmed MERS corona virus infected patients who were admitted into ICU. It included 20 (62.50%) males and 12 (37.50%) females. The mean age was 43.99 ± 13.03 years. Diagnosis was done by real-time reverse transcription polymerase chain reaction (rRT-PCR) test for corona virus on throat swab, sputum, tracheal aspirate, or bronchoalveolar lavage specimens. Clinical characteristics, co-morbidities and outcome were reported for all subjects.. Most MERS corona patients present with fever, cough, dyspnea, sore throat, runny nose and sputum. The presence of abdominal symptoms may indicate bad prognosis. Prolonged duration of symptoms before patients' hospitalization, prolonged duration of mechanical ventilation and hospital stay, bilateral radiological pulmonary infiltrates, and hypoxemic respiratory failure were found to be strong predictors of mortality in such patients. Also, old age, current smoking, smoking severity, presence of associated co-morbidities like obesity, diabetes mellitus, chronic heart diseases, COPD, malignancy, renal failure, renal transplantation and liver cirrhosis are associated with a poor outcome of ICU admitted MERS corona virus infected patients.. Plasma HO-1, ferritin, p21, and NQO1 were all elevated at baseline in CKD participants. Plasma HO-1 and urine NQO1 levels each inversely correlated with eGFR (. SnPP can be safely administered and, after its injection, the resulting changes in plasma HO-1, NQO1, ferritin, and p21 concentrations can provide information as to antioxidant gene responsiveness/reserves in subjects with and without kidney disease.. A Study with RBT-1, in Healthy Volunteers and Subjects with Stage 3-4 Chronic Kidney Disease, NCT0363002 and NCT03893799.. HFNC did not significantly modify work of breathing in healthy subjects. However, a significant reduction in the minute volume was achieved, capillary [Formula: see text] remaining constant, which suggests a reduction in dead-space ventilation with flows > 20 L/min. (ClinicalTrials.gov registration NCT02495675).. 3 组患者手术时间、术中显性失血量及术后 1 周血红蛋白下降量比较差异均无统计学意义（. 对于肥胖和超重的膝关节单间室骨关节炎患者，采用 UKA 术后可获满意短中期疗效，远期疗效尚需进一步随访观察。.. Decreased muscle strength was identified at both time points in patients with hEDS/HSD. The evolution of most muscle strength parameters over time did not significantly differ between groups. Future studies should focus on the effectiveness of different types of muscle training strategies in hEDS/HSD patients.. These findings support previous adverse findings of e-cigarette exposure on neurodevelopment in a mouse model and provide substantial evidence of persistent adverse behavioral and neuroimmunological consequences to adult offspring following maternal e-cigarette exposure during pregnancy. https://doi.org/10.1289/EHP6067.. This RCT directly compares a neoadjuvant chemotherapy regimen with a standard CROSS regimen in terms of overall survival for patients with locally advanced ESCC. The results of this RCT will provide an answer for the controversy regarding the survival benefits between the two treatment strategies.. NCT04138212, date of registration: October 24, 2019.. Results of current investigation indicated that milk type and post fermentation cooling patterns had a pronounced effect on antioxidant characteristics, fatty acid profile, lipid oxidation and textural characteristics of yoghurt. Buffalo milk based yoghurt had more fat, protein, higher antioxidant capacity and vitamin content. Antioxidant and sensory characteristics of T. If milk is exposed to excessive amounts of light, Vitamins B. The two concentration of ZnO nanoparticles in the ambient air produced two different outcomes. The lower concentration resulted in significant increases in Zn content of the liver while the higher concentration significantly increased Zn in the lungs (p < 0.05). Additionally, at the lower concentration, Zn content was found to be lower in brain tissue (p < 0.05). Using TEM/EDX we detected ZnO nanoparticles inside the cells in the lungs, kidney and liver. Inhaling ZnO NP at the higher concentration increased the levels of mRNA of the following genes in the lungs: Mt2 (2.56 fold), Slc30a1 (1.52 fold) and Slc30a5 (2.34 fold). At the lower ZnO nanoparticle concentration, only Slc30a7 mRNA levels in the lungs were up (1.74 fold). Thus the two air concentrations of ZnO nanoparticles produced distinct effects on the expression of the Zn-homeostasis related genes.. Until adverse health effects of ZnO nanoparticles deposited in organs such as lungs are further investigated and/or ruled out, the exposure to ZnO nanoparticles in aerosols should be avoided or minimised.

Topics: A549 Cells; Acetylmuramyl-Alanyl-Isoglutamine; Acinetobacter baumannii; Acute Lung Injury; Adaptor Proteins, Signal Transducing; Adenine; Adenocarcinoma; Adipogenesis; Administration, Cutaneous; Administration, Ophthalmic; Adolescent; Adsorption; Adult; Aeromonas hydrophila; Aerosols; Aged; Aged, 80 and over; Aging; Agriculture; Air Pollutants; Air Pollution; Airway Remodeling; Alanine Transaminase; Albuminuria; Aldehyde Dehydrogenase 1 Family; Algorithms; AlkB Homolog 2, Alpha-Ketoglutarate-Dependent Dioxygenase; Alzheimer Disease; Amino Acid Sequence; Ammonia; Ammonium Compounds; Anaerobiosis; Anesthetics, Dissociative; Anesthetics, Inhalation; Animals; Anti-Bacterial Agents; Anti-HIV Agents; Anti-Infective Agents; Anti-Inflammatory Agents; Antibiotics, Antineoplastic; Antibodies, Antineutrophil Cytoplasmic; Antibodies, Monoclonal, Humanized; Antifungal Agents; Antigens, Bacterial; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Antioxidants; Antitubercular Agents; Antiviral Agents; Apolipoproteins E; Apoptosis; Arabidopsis; Arabidopsis Proteins; Arsenic; Arthritis, Rheumatoid; Asthma; Atherosclerosis; ATP-Dependent Proteases; Attitude of Health Personnel; Australia; Austria; Autophagy; Axitinib; Bacteria; Bacterial Outer Membrane Proteins; Bacterial Proteins; Bacterial Toxins; Bacterial Typing Techniques; Bariatric Surgery; Base Composition; Bayes Theorem; Benzoxazoles; Benzylamines; beta Catenin; Betacoronavirus; Betula; Binding Sites; Biological Availability; Biological Oxygen Demand Analysis; Biomarkers; Biomarkers, Tumor; Biopsy; Bioreactors; Biosensing Techniques; Birth Weight; Blindness; Blood Chemical Analysis; Blood Gas Analysis; Blood Glucose; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Blood-Brain Barrier; Blotting, Western; Body Mass Index; Body Weight; Bone and Bones; Bone Density; Bone Resorption; Borates; Brain; Brain Infarction; Brain Injuries, Traumatic; Brain Neoplasms; Breakfast; Breast Milk Expression; Breast Neoplasms; Bronchi; Bronchoalveolar Lavage Fluid; Buffaloes; Cadherins; Calcification, Physiologic; Calcium Compounds; Calcium, Dietary; Cannula; Caprolactam; Carbon; Carbon Dioxide; Carboplatin; Carcinogenesis; Carcinoma, Ductal; Carcinoma, Ehrlich Tumor; Carcinoma, Hepatocellular; Carcinoma, Non-Small-Cell Lung; Carcinoma, Pancreatic Ductal; Carcinoma, Renal Cell; Cardiovascular Diseases; Carps; Carrageenan; Case-Control Studies; Catalysis; Catalytic Domain; Cattle; CD8-Positive T-Lymphocytes; Cell Adhesion; Cell Cycle Proteins; Cell Death; Cell Differentiation; Cell Line; Cell Line, Tumor; Cell Movement; Cell Nucleus; Cell Phone Use; Cell Proliferation; Cell Survival; Cell Transformation, Neoplastic; Cell Transformation, Viral; Cells, Cultured; Cellulose; Chemical Phenomena; Chemoradiotherapy; Child; Child Development; Child, Preschool; China; Chitosan; Chlorocebus aethiops; Cholecalciferol; Chromatography, Liquid; Circadian Clocks; Circadian Rhythm; Circular Dichroism; Cisplatin; Citric Acid; Clinical Competence; Clinical Laboratory Techniques; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Clostridioides difficile; Clostridium Infections; Coculture Techniques; Cohort Studies; Cold Temperature; Colitis; Collagen Type I; Collagen Type I, alpha 1 Chain; Collagen Type XI; Color; Connective Tissue Diseases; Copper; Coronary Angiography; Coronavirus 3C Proteases; Coronavirus Infections; Cost of Illness; Counselors; COVID-19; COVID-19 Testing; Creatine Kinase; Creatinine; Cross-Over Studies; Cross-Sectional Studies; Cryoelectron Microscopy; Cryosurgery; Crystallography, X-Ray; Cues; Cultural Competency; Cultural Diversity; Curriculum; Cyclic AMP Response Element-Binding Protein; Cyclin-Dependent Kinase Inhibitor p21; Cycloparaffins; Cysteine Endopeptidases; Cytokines; Cytoplasm; Cytoprotection; Databases, Factual; Denitrification; Deoxycytidine; Diabetes Complications; Diabetes Mellitus; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diagnosis, Differential; Diatoms; Diet; Diet, High-Fat; Dietary Exposure; Diffusion Magnetic Resonance Imaging; Diketopiperazines; Dipeptidyl Peptidase 4; Dipeptidyl-Peptidase IV Inhibitors; Disease Models, Animal; Disease Progression; Disease-Free Survival; DNA; DNA Damage; DNA Glycosylases; DNA Repair; DNA-Binding Proteins; DNA, Bacterial; DNA, Viral; Docetaxel; Dose Fractionation, Radiation; Dose-Response Relationship, Drug; Down-Regulation; Doxorubicin; Drosophila; Drosophila melanogaster; Drug Carriers; Drug Delivery Systems; Drug Liberation; Drug Repositioning; Drug Resistance, Bacterial; Drug Resistance, Multiple, Bacterial; Drug Resistance, Neoplasm; Drug Screening Assays, Antitumor; Drug Synergism; Drug Therapy, Combination; Edema; Edible Grain; Education, Graduate; Education, Medical, Graduate; Education, Pharmacy; Ehlers-Danlos Syndrome; Electron Transport Complex III; Electron Transport Complex IV; Electronic Nicotine Delivery Systems; Emergency Service, Hospital; Empathy; Emulsions; Endothelial Cells; Endurance Training; Energy Intake; Enterovirus A, Human; Environment; Environmental Monitoring; Enzyme Assays; Enzyme Inhibitors; Epithelial Cells; Epithelial-Mesenchymal Transition; Epoxide Hydrolases; Epoxy Compounds; Erythrocyte Count; Erythrocytes; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Esophagectomy; Estrogens; Etanercept; Ethiopia; Ethnicity; Ethylenes; Exanthema; Exercise; Exercise Test; Exercise Tolerance; Extracellular Matrix; Extracorporeal Membrane Oxygenation; Eye Infections, Fungal; False Negative Reactions; Fatty Acids; Fecal Microbiota Transplantation; Feces; Female; Femur Neck; Fermentation; Ferritins; Fetal Development; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Fibroblasts; Fibroins; Fish Proteins; Flavanones; Flavonoids; Focus Groups; Follow-Up Studies; Food Handling; Food Supply; Food, Formulated; Forced Expiratory Volume; Forests; Fractures, Bone; Fruit and Vegetable Juices; Fusobacteria; G1 Phase Cell Cycle Checkpoints; G2 Phase Cell Cycle Checkpoints; Gamma Rays; Gastrectomy; Gastrointestinal Microbiome; Gastrointestinal Stromal Tumors; Gefitinib; Gels; Gemcitabine; Gene Amplification; Gene Expression; Gene Expression Regulation; Gene Expression Regulation, Bacterial; Gene Expression Regulation, Neoplastic; Gene Expression Regulation, Plant; Gene Knockdown Techniques; Gene-Environment Interaction; Genotype; Germany; Glioma; Glomerular Filtration Rate; Glucagon; Glucocorticoids; Glycemic Control; Glycerol; Glycogen Synthase Kinase 3 beta; Glycolipids; Glycolysis; Goblet Cells; Gram-Negative Bacterial Infections; Granulocyte Colony-Stimulating Factor; Graphite; Greenhouse Effect; Guanidines; Haemophilus influenzae; HCT116 Cells; Health Knowledge, Attitudes, Practice; Health Personnel; Health Services Accessibility; Health Services Needs and Demand; Health Status Disparities; Healthy Volunteers; Heart Failure; Heart Rate; Heart Transplantation; Heart-Assist Devices; HEK293 Cells; Heme; Heme Oxygenase-1; Hemolysis; Hemorrhage; Hepatitis B; Hepatitis B e Antigens; Hepatitis B Surface Antigens; Hepatitis B virus; Hepatitis B, Chronic; Hepatocytes; Hexoses; High-Throughput Nucleotide Sequencing; Hippo Signaling Pathway; Histamine; Histamine Agonists; Histidine; Histone Deacetylase 2; HIV Infections; HIV Reverse Transcriptase; HIV-1; Homebound Persons; Homeodomain Proteins; Homosexuality, Male; Hospice and Palliative Care Nursing; HSP70 Heat-Shock Proteins; Humans; Hyaluronan Receptors; Hydrogen; Hydrogen Peroxide; Hydrogen-Ion Concentration; Hydrolysis; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypoglycemia; Hypoglycemic Agents; Hypoxia; Idiopathic Interstitial Pneumonias; Imaging, Three-Dimensional; Imatinib Mesylate; Immunotherapy; Implementation Science; Incidence; INDEL Mutation; Induced Pluripotent Stem Cells; Industrial Waste; Infant; Infant, Newborn; Inflammation; Inflammation Mediators; Infliximab; Infusions, Intravenous; Inhibitory Concentration 50; Injections; Insecticides; Insulin-Like Growth Factor Binding Protein 5; Insulin-Secreting Cells; Interleukin-1; Interleukin-17; Interleukin-8; Internship and Residency; Intestines; Intracellular Signaling Peptides and Proteins; Ion Transport; Iridaceae; Iridoid Glucosides; Islets of Langerhans Transplantation; Isodon; Isoflurane; Isotopes; Italy; Joint Instability; Ketamine; Kidney; Kidney Failure, Chronic; Kidney Function Tests; Kidney Neoplasms; Kinetics; Klebsiella pneumoniae; Knee Joint; Kruppel-Like Factor 4; Kruppel-Like Transcription Factors; Lactate Dehydrogenase 5; Laparoscopy; Laser Therapy; Lasers, Semiconductor; Lasers, Solid-State; Laurates; Lead; Leukocyte L1 Antigen Complex; Leukocytes, Mononuclear; Light; Lipid Peroxidation; Lipopolysaccharides; Liposomes; Liver; Liver Cirrhosis; Liver Neoplasms; Liver Transplantation; Locomotion; Longitudinal Studies; Lopinavir; Lower Urinary Tract Symptoms; Lubricants; Lung; Lung Diseases, Interstitial; Lung Neoplasms; Lymphocyte Activation; Lymphocytes, Tumor-Infiltrating; Lymphoma, Mantle-Cell; Lysosomes; Macrophages; Male; Manganese Compounds; MAP Kinase Kinase 4; Mass Screening; Maternal Health; Medicine, Chinese Traditional; Melanoma, Experimental; Memantine; Membrane Glycoproteins; Membrane Proteins; Mesenchymal Stem Cell Transplantation; Metal Nanoparticles; Metalloendopeptidases; Metalloporphyrins; Methadone; Methane; Methicillin-Resistant Staphylococcus aureus; Mexico; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Inbred ICR; Mice, Knockout; Mice, Nude; Mice, SCID; Mice, Transgenic; Microarray Analysis; Microbial Sensitivity Tests; Microbiota; Micronutrients; MicroRNAs; Microscopy, Confocal; Microsomes, Liver; Middle Aged; Milk; Milk, Human; Minority Groups; Mitochondria; Mitochondrial Membranes; Mitochondrial Proteins; Models, Animal; Models, Molecular; Molecular Conformation; Molecular Docking Simulation; Molecular Dynamics Simulation; Molecular Epidemiology; Molecular Structure; Molecular Weight; Multilocus Sequence Typing; Multimodal Imaging; Muscle Strength; Muscle, Skeletal; Muscular Diseases; Mutation; Mycobacterium tuberculosis; Myocardial Stunning; Myristates; NAD(P)H Dehydrogenase (Quinone); Nanocomposites; Nanogels; Nanoparticles; Nanotechnology; Naphthalenes; Nasal Cavity; National Health Programs; Necrosis; Needs Assessment; Neoadjuvant Therapy; Neonicotinoids; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasm Proteins; Neoplasm Recurrence, Local; Neoplasm Staging; Neoplasm Transplantation; Neoplasms; Neoplastic Stem Cells; Netherlands; Neuroblastoma; Neuroprotective Agents; Neutrophils; NF-kappa B; NFATC Transcription Factors; Nicotiana; Nicotine; Nitrates; Nitrification; Nitrites; Nitro Compounds; Nitrogen; Nitrogen Dioxide; North Carolina; Nuclear Magnetic Resonance, Biomolecular; Nuclear Proteins; Nucleic Acid Hybridization; Nucleosomes; Nutrients; Obesity; Obesity, Morbid; Oceans and Seas; Oncogene Protein v-akt; Oncogenes; Oocytes; Open Reading Frames; Osteoclasts; Osteogenesis; Osteoporosis; Osteoporosis, Postmenopausal; Outpatients; Ovarian Neoplasms; Ovariectomy; Overweight; Oxazines; Oxidants; Oxidation-Reduction; Oxidative Stress; Oxides; Oxidoreductases; Oxygen; Oxygen Inhalation Therapy; Oxygenators, Membrane; Ozone; Paclitaxel; Paenibacillus; Pain Measurement; Palliative Care; Pancreatic Neoplasms; Pandemics; Parasympathetic Nervous System; Particulate Matter; Pasteurization; Patient Preference; Patient Satisfaction; Pediatric Obesity; Permeability; Peroxiredoxins; Peroxynitrous Acid; Pharmaceutical Services; Pharmacists; Pharmacy; Phaseolus; Phenotype; Phoeniceae; Phosphates; Phosphatidylinositol 3-Kinases; Phospholipid Transfer Proteins; Phospholipids; Phosphorus; Phosphorylation; Photoperiod; Photosynthesis; Phylogeny; Physical Endurance; Physicians; Pilot Projects; Piperidines; Pituitary Adenylate Cyclase-Activating Polypeptide; Plant Extracts; Plant Leaves; Plant Proteins; Plant Roots; Plaque, Atherosclerotic; Pneumonia; Pneumonia, Viral; Point-of-Care Testing; Polyethylene Glycols; Polymers; Polysorbates; Pore Forming Cytotoxic Proteins; Positron Emission Tomography Computed Tomography; Positron-Emission Tomography; Postprandial Period; Poverty; Pre-Exposure Prophylaxis; Prediabetic State; Predictive Value of Tests; Pregnancy; Pregnancy Trimester, First; Pregnancy, High-Risk; Prenatal Exposure Delayed Effects; Pressure; Prevalence; Primary Graft Dysfunction; Primary Health Care; Professional Role; Professionalism; Prognosis; Progression-Free Survival; Prolactin; Promoter Regions, Genetic; Proof of Concept Study; Proportional Hazards Models; Propylene Glycol; Prospective Studies; Prostate; Protein Binding; Protein Biosynthesis; Protein Isoforms; Protein Kinase Inhibitors; Protein Phosphatase 2; Protein Processing, Post-Translational; Protein Serine-Threonine Kinases; Protein Structure, Tertiary; Protein Transport; Proteoglycans; Proteome; Proto-Oncogene Proteins c-akt; Proto-Oncogene Proteins c-myc; Proto-Oncogene Proteins c-ret; Proto-Oncogene Proteins p21(ras); Proton Pumps; Protons; Protoporphyrins; Pseudomonas aeruginosa; Pseudomonas fluorescens; Pulmonary Artery; Pulmonary Disease, Chronic Obstructive; Pulmonary Gas Exchange; Pulmonary Veins; Pyrazoles; Pyridines; Pyrimidines; Qualitative Research; Quinoxalines; Rabbits; Random Allocation; Rats; Rats, Sprague-Dawley; Rats, Wistar; Receptors, Histamine H3; Receptors, Immunologic; Receptors, Transferrin; Recombinant Proteins; Recurrence; Reference Values; Referral and Consultation; Regional Blood Flow; Registries; Regulon; Renal Insufficiency, Chronic; Reperfusion Injury; Repressor Proteins; Reproducibility of Results; Republic of Korea; Research Design; Resistance Training; Respiration, Artificial; Respiratory Distress Syndrome; Respiratory Insufficiency; Resuscitation; Retinal Dehydrogenase; Retreatment; Retrospective Studies; Reverse Transcriptase Inhibitors; Rhinitis, Allergic; Ribosomal Proteins; Ribosomes; Risk Assessment; Risk Factors; Ritonavir; Rivers; RNA Interference; RNA-Seq; RNA, Messenger; RNA, Ribosomal, 16S; RNA, Small Interfering; Rosuvastatin Calcium; Rural Population; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Salivary Ducts; Salivary Gland Neoplasms; San Francisco; SARS-CoV-2; Satiation; Satiety Response; Schools; Schools, Pharmacy; Seasons; Seawater; Selection, Genetic; Sequence Analysis, DNA; Serine-Threonine Kinase 3; Sewage; Sheep; Sheep, Domestic; Shock, Hemorrhagic; Signal Transduction; Silver; Silymarin; Single Photon Emission Computed Tomography Computed Tomography; Sirolimus; Sirtuin 1; Skin; Skin Neoplasms; Skin Physiological Phenomena; Sleep Initiation and Maintenance Disorders; Social Class; Social Participation; Social Support; Soil; Soil Microbiology; Solutions; Somatomedins; Soot; Specimen Handling; Spectrophotometry, Ultraviolet; Spectroscopy, Fourier Transform Infrared; Spectrum Analysis; Spinal Fractures; Spirometry; Staphylococcus aureus; STAT1 Transcription Factor; STAT3 Transcription Factor; Streptomyces coelicolor; Stress, Psychological; Stroke; Stroke Volume; Structure-Activity Relationship; Students, Medical; Students, Pharmacy; Substance Abuse Treatment Centers; Sulfur Dioxide; Surface Properties; Surface-Active Agents; Surveys and Questionnaires; Survival Analysis; Survival Rate; Survivin; Sweden; Swine; Swine, Miniature; Sympathetic Nervous System; T-Lymphocytes, Regulatory; Talaromyces; Tandem Mass Spectrometry; tau Proteins; Telemedicine; Telomerase; Telomere; Telomere Homeostasis; Temperature; Terminally Ill; Th1 Cells; Thiamethoxam; Thiazoles; Thiophenes; Thioredoxin Reductase 1; Thrombosis; Thulium; Thyroid Cancer, Papillary; Thyroid Carcinoma, Anaplastic; Thyroid Neoplasms; Time Factors; Titanium; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed; TOR Serine-Threonine Kinases; Transcription Factor AP-1; Transcription Factors; Transcription, Genetic; Transcriptional Activation; Transcriptome; Transforming Growth Factor beta1; Transistors, Electronic; Translational Research, Biomedical; Transplantation Tolerance; Transplantation, Homologous; Transportation; Treatment Outcome; Tretinoin; Tuberculosis, Multidrug-Resistant; Tuberculosis, Pulmonary; Tubulin Modulators; Tumor Microenvironment; Tumor Necrosis Factor Inhibitors; Tumor Necrosis Factor-alpha; Twins; Ultrasonic Therapy; Ultrasonography; Ultraviolet Rays; United States; Up-Regulation; Uranium; Urethra; Urinary Bladder; Urodynamics; Uromodulin; Uveitis; Vasoconstrictor Agents; Ventricular Function, Left; Vero Cells; Vesicular Transport Proteins; Viral Nonstructural Proteins; Visual Acuity; Vital Capacity; Vitamin D; Vitamin D Deficiency; Vitamin K 2; Vitamins; Volatilization; Voriconazole; Waiting Lists; Waste Disposal, Fluid; Wastewater; Water Pollutants, Chemical; Whole Genome Sequencing; Wine; Wnt Signaling Pathway; Wound Healing; Wounds and Injuries; WW Domains; X-linked Nuclear Protein; X-Ray Diffraction; Xanthines; Xenograft Model Antitumor Assays; YAP-Signaling Proteins; Yogurt; Young Adult; Zebrafish; Zebrafish Proteins; Ziziphus

It is well-known for a long-time, that intensive exercise is favourable for many metabolic parameters. Up-till now the exact mechanism has not been clarified. Recently it has turned out, that the muscular system is an extended endocrine organ, which, during contraction, secretes many hundred peptides, so called adipomyokines into the blood stream. Many of them improve glucose-utilization of the muscular system, and insulin-sensitivity, via endocrine, paracrine, or autocrine pathways. Worldwide intensive research takes place to clear up the exact pathomechanism of these processes. It came to light: 1. The newly discovered adipomyokine, irisin induces "browning" of beige precursor fat-cells, which are present in white adipose tissue. The developed beige adipose tissue by this way disposes with the advantegous properties of the brown adipose tissue. Taking together these facts, irisin might be a therapeutic choice in treating certain diseases, caused by inactive life-style. 2. Therapeutic application of brown adipose tissue in obesity, metabolic syndrome, and type 2 diabetes seems to be successful. This mechanism is based on removal of unnecessary calories via thermogenesis. 3. The role of myostatin, which is also produced by muscle contraction, is contradictory. It is not clear, why does the muscle system produce damaging product for the metabolism. On the other hand, inhibition of myostatin might be a therapeutic option. It is still questionable, whether the other hundreds of myokines could possess practicable roles on glucose, lipid, insulin secretion/effects. At present one can establish, that regular exercise is essential for the everyday practise, in order to optimise quality of life.. Régóta ismeretes, hogy az intenzív izommunka számos metabolikus paramétert kedvezően befolyásol. E folyamat mechanizmusa eddig nem volt tisztázott. Újabban kiderült, hogy a vázizomzat kiterjedt endokrin szerv, amely kontrakciója során több száz adipomiokint szekretál a véráramba, amelyek egy része endokrin, parakrin vagy autokrin úton javítja a vázizomzat glükózfelhasználását, fokozza inzulinérzékenységét. Világszerte intenzív kutatás igyekszik e folyamatok pontos mechanizmusát felderíteni. Három fontos területen történt előrehaladás: 1. Az újonnan felfedezett adipomiokin, az irisin a fehér zsírszövetben jelen lévő bézs prekurzor zsírsejtekben „barnásítást” indít meg, és az így létrejött bézs zsírszövet a továbbiakban a barna zsírszövet előnyös anyagcserehatásaival rendelkezik. Az irisin perspektivikusan terápiás opció lehet az inaktív életmód okozta betegségek kezelésében. 2. Kiderült, hogy a barna zsírszövet terápiás alkalmazása obesitasban, metabolikus szindrómában és 2-es típusú diabetesben eredményes, ami a felesleges kalóriák hőtermelés útján való eliminálásán alapszik. 3. Az ugyancsak kontrakció hatására termelődő myostatin szerepe ellentmondásos, nem világos, hogy az izomzat miért expresszál magára az izomzatra és az anyagcserére is káros anyagot, ugyanakkor a myostatin gátlása terápiásan felhasználható lehet. Kérdéses, hogy a többi sok száz miokinnek milyen szerepe lehet a fontos metabolikus paraméterek (glükóz, inzulin, lipidek) szekréciójában és hatásában, azonban a mindennapi gyakorlat számára már most leszögezhető, hogy a mozgás elengedhetetlen az életminőség optimalizálása szempontjából. Orv. Hetil., 2014, 155(37), 1469–1477.

Topics: Adipose Tissue, Brown; Adipose Tissue, White; Animals; Body Mass Index; Diabetes Mellitus, Type 2; Dietary Fats; Energy Metabolism; Fibronectins; Follistatin; Glucose; Humans; Inflammation; Insulin Resistance; Interleukin-15; Interleukin-6; Interleukin-8; Metabolic Syndrome; Muscle Contraction; Muscle, Skeletal; Myocardium; Myostatin; Obesity; Physical Exertion; Sedentary Behavior

Diabetes is a complex disease that affects many organs directly or indirectly. Type 2 diabetes mellitus is characterized by insulin resistance with a relative deficiency in insulin secretion. It has become apparent that inter-organ communication is of great importance in the pathophysiology of diabetes. Far from being an inert tissue in terms of inter-organ communication, it is now recognized that skeletal muscle can secrete so-called myokines that can impact on the function of distant organs/tissues both favourably and unfavourably. We have proposed that communication between insulin-resistant skeletal muscle and β-cells occurs in diabetes. This is a novel route of communication that we further suggest is modified by the prevailing degree of insulin resistance of skeletal muscle. This review focuses on the various myokines [interleukin-6 (IL-6), tumor necrosis factor-α, CXCL10, follistatin and IL-8] which have been identified either after different types of exercise or in the secretome from control and insulin-resistant human skeletal myotubes. We will also summarize studies on the impact of several myokines on pancreatic β-cell proliferation, survival and function.

Topics: Animals; Cell Proliferation; Chemokine CXCL10; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Follistatin; Humans; Insulin; Insulin Resistance; Insulin-Secreting Cells; Interleukin-6; Interleukin-8; Male; Muscle Fibers, Skeletal; Rats; Tumor Necrosis Factor-alpha

Circulation on blood extracorporeally through plastic tubing activates several pathways including systemic inflammation and oxidative stress. These phenomena are suspected to participate to neurological and cardiovascular side effects observed in the patients under cardiopulmonary bypass (CPB). A direct relationship, in diabetic patients, between hyperglycemia and morbidity and mortality has been established. However, it is still unclear whether perioperative hyperglycemia has a direct effect on adverse events in cardiac surgery. The purpose of this study was to determine the influence of hyperglycemia on inflammation and oxidative stress in patients under CPB during cardiac surgery.. Control patients (n=17) and diabetic (type 2) patients (n=13) were included in this study. Blood samples were drawn before, during and after the CPB. Oxidative stress was evaluated in the plasma by direct and indirect approaches. Direct detection of ascorbyl radicals was assessed by electron spin resonance spectroscopy. An index: ascorbyl radical/vitamin C ratio is an indicator of the degree of oxidative stress taking place in the plasma. Oxygen radical absorbing capacity (ORAC) values were used as measurement of antioxidant capacity of the plasma. To determine inflammation profile of patients, we measure the evolution of plasma concentration of interleukin 8 (IL-8).. During cross clamping and post-CPB, the index ascorbyl radical/vitamin C is increased; the value of the index is more significant in diabetic patients. Concomitantly, ORAC values decreased in all the patients during cross clamping (p<0.05). Results concerning inflammatory index showed that IL-8 levels increased during the CPB.. In conclusion, the current study indicates that a systemic oxidative stress occurs during CPB and post-CPB periods and that in patients with type 2 diabetes mellitus, the systemic oxidative stress was increased.

Topics: Aged; Ascorbic Acid; Cardiopulmonary Bypass; Dehydroascorbic Acid; Diabetes Mellitus, Type 2; Electron Spin Resonance Spectroscopy; Female; Glycated Hemoglobin; Heart Valve Prosthesis Implantation; Humans; Hyperglycemia; Interleukin-8; Male; Middle Aged; Oxidative Stress

Low-grade inflammation is central to coronary artery disease (CAD) and type 2 diabetes (T2D) and is reduced by exercise training. The objective of this study was to compare the anti-inflammatory potential of moderate-to-vigorous intensity continuous training (MICT) and high-intensity interval training (HIIT) in patients with CAD with or without T2D. The design and setting of this study is based on a secondary analysis of registered randomized clinical trial NCT02765568. Male patients with CAD were randomly assigned to either MICT or HIIT, with subgroups divided according to T2D status (non-T2D-HIIT n = 14 and non-T2D-MICT n = 13; T2D-HIIT n = 6 and T2D-MICT n = 5). The intervention was a 12-week cardiovascular rehabilitation program consisting of either MICT or HIIT (twice weekly sessions) and circulating cytokines measured pre- and post-training as inflammatory markers. The co-occurrence of CAD and T2D was associated with increased plasma IL-8 (p = 0.0331). There was an interaction between T2D and the effect of the training interventions on plasma FGF21 (p = 0.0368) and IL-6 (p = 0.0385), which were further reduced in the T2D groups. An interaction between T2D, training modalities, and the effect of time (p = 0.0415) was detected for SPARC, with HIIT increasing circulating concentrations in the control group, while lowering them in the T2D group, and the inverse occurring with MICT. The interventions also reduced plasma FGF21 (p = 0.0030), IL-6 (p = 0.0101), IL-8 (p = 0.0087), IL-10 (p < 0.0001), and IL-18 (p = 0.0009) irrespective of training modality or T2D status. HIIT and MICT resulted in similar reductions in circulating cytokines known to be increased in the context of low-grade inflammation in CAD patients, an effect more pronounced in patients with T2D for FGF21 and IL-6.

Topics: Coronary Artery Disease; Cytokines; Diabetes Mellitus, Type 2; Exercise; High-Intensity Interval Training; Humans; Inflammation; Interleukin-6; Interleukin-8; Male; Pilot Projects

The type 2 diabetes mellitus (T2DM) is an urgent global health problem. T2DM patients are in a state of high oxidative stress and inflammation. Vitamin D and glutathione (GSH) play crucial roles in antioxidation and anti-inflammation. However, T2DM patients have lower vitamin D and GSH levels than healthy persons. A randomized controlled trial was conducted to see the effect of the vitamin D supplementation on oxidative stress and inflammatory factors in T2DM patients. In this study, a total of 178 T2DM patients were randomly enrolled, 92 patients received regular treatment (T2DM group) and 86 patients in Vitamin D group received extra vitamin D 400 IU per day in addition to regular treatment. Serum vitamin D, GSH, GSH metabolic enzyme GCLC and GR, inflammatory factor MCP-1, and IL-8 levels were investigated. We found that the T2DM group has significantly higher concentrations of MCP-1 and IL-8 than those in the healthy donor group. After vitamin D supplementation for 90 days, T2DM patients had a 2-fold increase of GSH levels, from 2.72 ± 0.84 to 5.76 ± 3.19 μmol/ml, the concentration of MCP-1 decreased from 51.11 ± 20.86 to 25.42 ± 13.06 pg/ml, and IL-8 also decreased from 38.21 ± 21.76 to 16.05 ± 8.99 pg/ml. In conclusion, our study demonstrated that vitamin D could regulate the production of GSH, thereby reducing the serum levels of MCP-1 and IL-8, alleviating oxidative stress and inflammation, providing evidence of the necessity and feasibility of adjuvant vitamin D treatment among patients with T2DM. On the other hand, vitamin D and GSH levels have important diagnostic and prognostic values in T2DM patients.

Topics: Diabetes Mellitus, Type 2; Dietary Supplements; Glutathione; Humans; Inflammation; Interleukin-8; Oxidative Stress; Vitamin D; Vitamins

To compare 12 weeks of exercise training at two intensities on oxidative stress, antioxidants and inflammatory biomarkers in patients with type 2 diabetes (T2D).. Randomized trial.. Thirty-six participants with T2D were randomized to complete either 12 weeks of treadmill based high-intensity interval training (HIIT) or moderate-intensity continuous training (MICT), followed by 40 weeks of home-based training at the same intensities. Plasma inflammation, oxidative stress and antioxidant biomarkers (total F2-isoprostanes, protein carbonyls, total antioxidant capacity, glutathione peroxidase activity, interleukin-10, interleukin-6, interleukin-8 and TNF-α) were measured at baseline, 12-weeks and 1-year.. There were no significant changes (p>0.05) in oxidative stress and inflammation biomarkers from baseline to 12-weeks in either intervention. A decrease in total antioxidant capacity in the MICT group from baseline to 1-year by 0.05mmol/L (p=0.05) was observed. There was a significant difference (p<0.05) when groups were separated by sex with females in the MICT group having a 22.1% (p<0.05) decrease in protein carbonyls from baseline to 1-year.. HIIT and MICT had no acute effect on oxidative stress and inflammatory biomarkers in patients with T2D.

Topics: Antioxidants; Biomarkers; Diabetes Mellitus, Type 2; Exercise Test; Female; Glutathione Peroxidase; High-Intensity Interval Training; Homeostasis; Humans; Interleukin-10; Interleukin-6; Interleukin-8; Male; Middle Aged; Oxidative Stress; Tumor Necrosis Factor-alpha

Middle East Respiratory Syndrome (MERS) is a novel respiratory illness firstly reported in Saudi Arabia in 2012. It is caused by a new corona virus, called MERS corona virus (MERS-CoV). Most people who have MERS-CoV infection developed severe acute respiratory illness.. This work is done to determine the clinical characteristics and the outcome of intensive care unit (ICU) admitted patients with confirmed MERS-CoV infection.. This study included 32 laboratory confirmed MERS corona virus infected patients who were admitted into ICU. It included 20 (62.50%) males and 12 (37.50%) females. The mean age was 43.99 ± 13.03 years. Diagnosis was done by real-time reverse transcription polymerase chain reaction (rRT-PCR) test for corona virus on throat swab, sputum, tracheal aspirate, or bronchoalveolar lavage specimens. Clinical characteristics, co-morbidities and outcome were reported for all subjects.. Most MERS corona patients present with fever, cough, dyspnea, sore throat, runny nose and sputum. The presence of abdominal symptoms may indicate bad prognosis. Prolonged duration of symptoms before patients' hospitalization, prolonged duration of mechanical ventilation and hospital stay, bilateral radiological pulmonary infiltrates, and hypoxemic respiratory failure were found to be strong predictors of mortality in such patients. Also, old age, current smoking, smoking severity, presence of associated co-morbidities like obesity, diabetes mellitus, chronic heart diseases, COPD, malignancy, renal failure, renal transplantation and liver cirrhosis are associated with a poor outcome of ICU admitted MERS corona virus infected patients.. Plasma HO-1, ferritin, p21, and NQO1 were all elevated at baseline in CKD participants. Plasma HO-1 and urine NQO1 levels each inversely correlated with eGFR (. SnPP can be safely administered and, after its injection, the resulting changes in plasma HO-1, NQO1, ferritin, and p21 concentrations can provide information as to antioxidant gene responsiveness/reserves in subjects with and without kidney disease.. A Study with RBT-1, in Healthy Volunteers and Subjects with Stage 3-4 Chronic Kidney Disease, NCT0363002 and NCT03893799.. HFNC did not significantly modify work of breathing in healthy subjects. However, a significant reduction in the minute volume was achieved, capillary [Formula: see text] remaining constant, which suggests a reduction in dead-space ventilation with flows > 20 L/min. (ClinicalTrials.gov registration NCT02495675).. 3 组患者手术时间、术中显性失血量及术后 1 周血红蛋白下降量比较差异均无统计学意义（. 对于肥胖和超重的膝关节单间室骨关节炎患者，采用 UKA 术后可获满意短中期疗效，远期疗效尚需进一步随访观察。.. Decreased muscle strength was identified at both time points in patients with hEDS/HSD. The evolution of most muscle strength parameters over time did not significantly differ between groups. Future studies should focus on the effectiveness of different types of muscle training strategies in hEDS/HSD patients.. These findings support previous adverse findings of e-cigarette exposure on neurodevelopment in a mouse model and provide substantial evidence of persistent adverse behavioral and neuroimmunological consequences to adult offspring following maternal e-cigarette exposure during pregnancy. https://doi.org/10.1289/EHP6067.. This RCT directly compares a neoadjuvant chemotherapy regimen with a standard CROSS regimen in terms of overall survival for patients with locally advanced ESCC. The results of this RCT will provide an answer for the controversy regarding the survival benefits between the two treatment strategies.. NCT04138212, date of registration: October 24, 2019.. Results of current investigation indicated that milk type and post fermentation cooling patterns had a pronounced effect on antioxidant characteristics, fatty acid profile, lipid oxidation and textural characteristics of yoghurt. Buffalo milk based yoghurt had more fat, protein, higher antioxidant capacity and vitamin content. Antioxidant and sensory characteristics of T. If milk is exposed to excessive amounts of light, Vitamins B. The two concentration of ZnO nanoparticles in the ambient air produced two different outcomes. The lower concentration resulted in significant increases in Zn content of the liver while the higher concentration significantly increased Zn in the lungs (p < 0.05). Additionally, at the lower concentration, Zn content was found to be lower in brain tissue (p < 0.05). Using TEM/EDX we detected ZnO nanoparticles inside the cells in the lungs, kidney and liver. Inhaling ZnO NP at the higher concentration increased the levels of mRNA of the following genes in the lungs: Mt2 (2.56 fold), Slc30a1 (1.52 fold) and Slc30a5 (2.34 fold). At the lower ZnO nanoparticle concentration, only Slc30a7 mRNA levels in the lungs were up (1.74 fold). Thus the two air concentrations of ZnO nanoparticles produced distinct effects on the expression of the Zn-homeostasis related genes.. Until adverse health effects of ZnO nanoparticles deposited in organs such as lungs are further investigated and/or ruled out, the exposure to ZnO nanoparticles in aerosols should be avoided or minimised.

Topics: A549 Cells; Acetylmuramyl-Alanyl-Isoglutamine; Acinetobacter baumannii; Acute Lung Injury; Adaptor Proteins, Signal Transducing; Adenine; Adenocarcinoma; Adipogenesis; Administration, Cutaneous; Administration, Ophthalmic; Adolescent; Adsorption; Adult; Aeromonas hydrophila; Aerosols; Aged; Aged, 80 and over; Aging; Agriculture; Air Pollutants; Air Pollution; Airway Remodeling; Alanine Transaminase; Albuminuria; Aldehyde Dehydrogenase 1 Family; Algorithms; AlkB Homolog 2, Alpha-Ketoglutarate-Dependent Dioxygenase; Alzheimer Disease; Amino Acid Sequence; Ammonia; Ammonium Compounds; Anaerobiosis; Anesthetics, Dissociative; Anesthetics, Inhalation; Animals; Anti-Bacterial Agents; Anti-HIV Agents; Anti-Infective Agents; Anti-Inflammatory Agents; Antibiotics, Antineoplastic; Antibodies, Antineutrophil Cytoplasmic; Antibodies, Monoclonal, Humanized; Antifungal Agents; Antigens, Bacterial; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Antioxidants; Antitubercular Agents; Antiviral Agents; Apolipoproteins E; Apoptosis; Arabidopsis; Arabidopsis Proteins; Arsenic; Arthritis, Rheumatoid; Asthma; Atherosclerosis; ATP-Dependent Proteases; Attitude of Health Personnel; Australia; Austria; Autophagy; Axitinib; Bacteria; Bacterial Outer Membrane Proteins; Bacterial Proteins; Bacterial Toxins; Bacterial Typing Techniques; Bariatric Surgery; Base Composition; Bayes Theorem; Benzoxazoles; Benzylamines; beta Catenin; Betacoronavirus; Betula; Binding Sites; Biological Availability; Biological Oxygen Demand Analysis; Biomarkers; Biomarkers, Tumor; Biopsy; Bioreactors; Biosensing Techniques; Birth Weight; Blindness; Blood Chemical Analysis; Blood Gas Analysis; Blood Glucose; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Blood-Brain Barrier; Blotting, Western; Body Mass Index; Body Weight; Bone and Bones; Bone Density; Bone Resorption; Borates; Brain; Brain Infarction; Brain Injuries, Traumatic; Brain Neoplasms; Breakfast; Breast Milk Expression; Breast Neoplasms; Bronchi; Bronchoalveolar Lavage Fluid; Buffaloes; Cadherins; Calcification, Physiologic; Calcium Compounds; Calcium, Dietary; Cannula; Caprolactam; Carbon; Carbon Dioxide; Carboplatin; Carcinogenesis; Carcinoma, Ductal; Carcinoma, Ehrlich Tumor; Carcinoma, Hepatocellular; Carcinoma, Non-Small-Cell Lung; Carcinoma, Pancreatic Ductal; Carcinoma, Renal Cell; Cardiovascular Diseases; Carps; Carrageenan; Case-Control Studies; Catalysis; Catalytic Domain; Cattle; CD8-Positive T-Lymphocytes; Cell Adhesion; Cell Cycle Proteins; Cell Death; Cell Differentiation; Cell Line; Cell Line, Tumor; Cell Movement; Cell Nucleus; Cell Phone Use; Cell Proliferation; Cell Survival; Cell Transformation, Neoplastic; Cell Transformation, Viral; Cells, Cultured; Cellulose; Chemical Phenomena; Chemoradiotherapy; Child; Child Development; Child, Preschool; China; Chitosan; Chlorocebus aethiops; Cholecalciferol; Chromatography, Liquid; Circadian Clocks; Circadian Rhythm; Circular Dichroism; Cisplatin; Citric Acid; Clinical Competence; Clinical Laboratory Techniques; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Clostridioides difficile; Clostridium Infections; Coculture Techniques; Cohort Studies; Cold Temperature; Colitis; Collagen Type I; Collagen Type I, alpha 1 Chain; Collagen Type XI; Color; Connective Tissue Diseases; Copper; Coronary Angiography; Coronavirus 3C Proteases; Coronavirus Infections; Cost of Illness; Counselors; COVID-19; COVID-19 Testing; Creatine Kinase; Creatinine; Cross-Over Studies; Cross-Sectional Studies; Cryoelectron Microscopy; Cryosurgery; Crystallography, X-Ray; Cues; Cultural Competency; Cultural Diversity; Curriculum; Cyclic AMP Response Element-Binding Protein; Cyclin-Dependent Kinase Inhibitor p21; Cycloparaffins; Cysteine Endopeptidases; Cytokines; Cytoplasm; Cytoprotection; Databases, Factual; Denitrification; Deoxycytidine; Diabetes Complications; Diabetes Mellitus; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diagnosis, Differential; Diatoms; Diet; Diet, High-Fat; Dietary Exposure; Diffusion Magnetic Resonance Imaging; Diketopiperazines; Dipeptidyl Peptidase 4; Dipeptidyl-Peptidase IV Inhibitors; Disease Models, Animal; Disease Progression; Disease-Free Survival; DNA; DNA Damage; DNA Glycosylases; DNA Repair; DNA-Binding Proteins; DNA, Bacterial; DNA, Viral; Docetaxel; Dose Fractionation, Radiation; Dose-Response Relationship, Drug; Down-Regulation; Doxorubicin; Drosophila; Drosophila melanogaster; Drug Carriers; Drug Delivery Systems; Drug Liberation; Drug Repositioning; Drug Resistance, Bacterial; Drug Resistance, Multiple, Bacterial; Drug Resistance, Neoplasm; Drug Screening Assays, Antitumor; Drug Synergism; Drug Therapy, Combination; Edema; Edible Grain; Education, Graduate; Education, Medical, Graduate; Education, Pharmacy; Ehlers-Danlos Syndrome; Electron Transport Complex III; Electron Transport Complex IV; Electronic Nicotine Delivery Systems; Emergency Service, Hospital; Empathy; Emulsions; Endothelial Cells; Endurance Training; Energy Intake; Enterovirus A, Human; Environment; Environmental Monitoring; Enzyme Assays; Enzyme Inhibitors; Epithelial Cells; Epithelial-Mesenchymal Transition; Epoxide Hydrolases; Epoxy Compounds; Erythrocyte Count; Erythrocytes; Escherichia coli; Escherichia coli Infections; Escherichia coli Proteins; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Esophagectomy; Estrogens; Etanercept; Ethiopia; Ethnicity; Ethylenes; Exanthema; Exercise; Exercise Test; Exercise Tolerance; Extracellular Matrix; Extracorporeal Membrane Oxygenation; Eye Infections, Fungal; False Negative Reactions; Fatty Acids; Fecal Microbiota Transplantation; Feces; Female; Femur Neck; Fermentation; Ferritins; Fetal Development; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Fibroblasts; Fibroins; Fish Proteins; Flavanones; Flavonoids; Focus Groups; Follow-Up Studies; Food Handling; Food Supply; Food, Formulated; Forced Expiratory Volume; Forests; Fractures, Bone; Fruit and Vegetable Juices; Fusobacteria; G1 Phase Cell Cycle Checkpoints; G2 Phase Cell Cycle Checkpoints; Gamma Rays; Gastrectomy; Gastrointestinal Microbiome; Gastrointestinal Stromal Tumors; Gefitinib; Gels; Gemcitabine; Gene Amplification; Gene Expression; Gene Expression Regulation; Gene Expression Regulation, Bacterial; Gene Expression Regulation, Neoplastic; Gene Expression Regulation, Plant; Gene Knockdown Techniques; Gene-Environment Interaction; Genotype; Germany; Glioma; Glomerular Filtration Rate; Glucagon; Glucocorticoids; Glycemic Control; Glycerol; Glycogen Synthase Kinase 3 beta; Glycolipids; Glycolysis; Goblet Cells; Gram-Negative Bacterial Infections; Granulocyte Colony-Stimulating Factor; Graphite; Greenhouse Effect; Guanidines; Haemophilus influenzae; HCT116 Cells; Health Knowledge, Attitudes, Practice; Health Personnel; Health Services Accessibility; Health Services Needs and Demand; Health Status Disparities; Healthy Volunteers; 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Infliximab; Infusions, Intravenous; Inhibitory Concentration 50; Injections; Insecticides; Insulin-Like Growth Factor Binding Protein 5; Insulin-Secreting Cells; Interleukin-1; Interleukin-17; Interleukin-8; Internship and Residency; Intestines; Intracellular Signaling Peptides and Proteins; Ion Transport; Iridaceae; Iridoid Glucosides; Islets of Langerhans Transplantation; Isodon; Isoflurane; Isotopes; Italy; Joint Instability; Ketamine; Kidney; Kidney Failure, Chronic; Kidney Function Tests; Kidney Neoplasms; Kinetics; Klebsiella pneumoniae; Knee Joint; Kruppel-Like Factor 4; Kruppel-Like Transcription Factors; Lactate Dehydrogenase 5; Laparoscopy; Laser Therapy; Lasers, Semiconductor; Lasers, Solid-State; Laurates; Lead; Leukocyte L1 Antigen Complex; Leukocytes, Mononuclear; Light; Lipid Peroxidation; Lipopolysaccharides; Liposomes; Liver; Liver Cirrhosis; Liver Neoplasms; Liver Transplantation; Locomotion; Longitudinal Studies; Lopinavir; Lower Urinary Tract Symptoms; Lubricants; Lung; Lung Diseases, Interstitial; Lung Neoplasms; Lymphocyte Activation; Lymphocytes, Tumor-Infiltrating; Lymphoma, Mantle-Cell; Lysosomes; Macrophages; Male; Manganese Compounds; MAP Kinase Kinase 4; Mass Screening; Maternal Health; Medicine, Chinese Traditional; Melanoma, Experimental; Memantine; Membrane Glycoproteins; Membrane Proteins; Mesenchymal Stem Cell Transplantation; Metal Nanoparticles; Metalloendopeptidases; Metalloporphyrins; Methadone; Methane; Methicillin-Resistant Staphylococcus aureus; Mexico; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Inbred ICR; Mice, Knockout; Mice, Nude; Mice, SCID; Mice, Transgenic; Microarray Analysis; Microbial Sensitivity Tests; Microbiota; Micronutrients; MicroRNAs; Microscopy, Confocal; Microsomes, Liver; Middle Aged; Milk; Milk, Human; Minority Groups; Mitochondria; Mitochondrial Membranes; Mitochondrial Proteins; Models, Animal; Models, Molecular; Molecular Conformation; Molecular Docking Simulation; Molecular Dynamics Simulation; Molecular Epidemiology; 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YAP-Signaling Proteins; Yogurt; Young Adult; Zebrafish; Zebrafish Proteins; Ziziphus

Exercise increases muscle derived Interleukin–6 (IL–6) leading to insulin secretion via glucagon-like peptide–1. IL–1 antagonism improves glycemia and decreases systemic inflammation including IL–6 in patients with type 2 diabetes. However, it is not known whether physiological, exercise-induced muscle-derived IL–6 is also regulated by the IL–1 system. Therefore we conducted a double blind, crossover study in 17 healthy male subjects randomized to receive either the IL–1 receptor antagonist IL-1Ra (anakinra) or placebo prior to an acute treadmill exercise. Muscle activity led to a 2–3 fold increase in serum IL–6 concentrations but anakinra had no effect on this exercise-induced IL–6. Furthermore, the IL–1 responsive inflammatory markers CRP, cortisol and MCP–1 remained largely unaffected by exercise and anakinra. We conclude that the beneficial effect of muscle-induced IL–6 is not meaningfully affected by IL–1 antagonism.. ClinicalTrials.gov NCT01771445.

Topics: Adult; C-Reactive Protein; Cell Line; Chemokines; Cross-Over Studies; Diabetes Mellitus, Type 2; Double-Blind Method; Exercise; Humans; Insulin-Secreting Cells; Interleukin-1beta; Interleukin-6; Interleukin-8; Male; Middle Aged; Muscle, Skeletal; Placebo Effect; Receptors, Interleukin-1; Recombinant Proteins; Serum

In this study, we examined whether inhibition of postprandial hyperglycemia by combination therapy with two drugs for reducing postprandial hyperglycemia, i.e., α-glucosidase inhibitor miglitol and dipeptidyl peptidase (DPP)-4 inhibitor sitagliptin, improves glycemic control and reduces the risk of cardiovascular disease (CVD) development.. We enrolled 32 type 2 diabetic Japanese patients with hemoglobin A1c (HbA1c) levels ranging from 6.9% to 10.5%, who had been treated for at least 2 months with 50mg miglitol (t.i.d.) or 50 mg sitagliptin (q.d.). Following a monotherapy period with either miglitol (Group-M) or sitagliptin (Group-S) for 1 month, the patients were subjected to combination therapy with sitagliptin and miglitol for 3 months. Meal tolerance tests were performed at the end of the monotherapy and combination therapy.. Combination therapy for 3 months after monotherapy reduced HbA1c (changes: Group-M: -1.3%±0.7%, P<0.001; Group-S: -0.6%±0.5%, P<0.001) and glycoalbumin levels and increased 1,5-anhydroglucitol concentrations in the blood. In the meal tolerance tests, circulating active glucagon-like peptide-1 levels were elevated in both groups, while active glucose-dependent insulinotropic polypeptide levels were reduced by combination therapy in the group with add-on miglitol therapy. The plasma protein concentrations of interleukin (IL)-8 and adhesion molecules (sE-selectin and sVCAM-1) were reduced by switching to the combination therapy, in particular with the add-on miglitol therapy.. Our results suggest that combination therapy with miglitol and sitagliptin improves glycemic control and reduces the circulating protein concentrations of IL-8, sE-selectin, and sVCAM-1 in type 2 diabetic Japanese patients.

Topics: 1-Deoxynojirimycin; Adult; Aged; Asian People; Biomarkers; Blood Glucose; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Drug Therapy, Combination; E-Selectin; Female; Glycoside Hydrolase Inhibitors; Humans; Hypoglycemic Agents; Incretins; Interleukin-8; Japan; Male; Middle Aged; Prospective Studies; Pyrazines; Risk Factors; Sitagliptin Phosphate; Triazoles; Vascular Cell Adhesion Molecule-1

At the time of diagnosis, almost 80% of pancreatic cancer patients present with new-onset type 2 diabetes (T2D) or impaired glucose tolerance. T2D and pancreatic cancer are both associated with low-grade inflammation. Tumour-associated macrophages (TAMs) have a key role in cancer-related inflammation, immune escape, matrix remodelling and metastasis. In this study, the interplay between tumour cells and immune cells under the influence of different glucose levels was investigated. Human peripheral blood mononuclear cells were exposed in vitro to conditioned medium from BxPC-3 human pancreatic cancer cells, in normal (5 mM) or high (25 mM) glucose levels. Flow cytometry analyses demonstrated that tumour-derived factors stimulated differentiation of macrophages, with a mixed classical (M1-like) and alternatively activated (M2-like) phenotype polarisation (CD11c(+)CD206(+)). High-glucose conditions further enhanced the tumour-driven macrophage enrichment and associated interleukin (IL)-6 and IL-8 cytokine levels. In addition, hyperglycaemia enhanced the responsiveness of tumour-educated macrophages to lipopolysaccharide, with elevated cytokine secretion compared with normal glucose levels. Tumour-educated macrophages were found to promote pancreatic cancer cell invasion in vitro, which was significantly enhanced at high glucose. The anti-diabetic drug metformin shifted the macrophage phenotype polarisation and reduced the tumour cell invasion at normal, but not high, glucose levels. In conclusion, this study demonstrates that pancreatic cancer cells stimulate differentiation of macrophages with pro-tumour properties that are further enhanced by hyperglycaemia. These findings highlight important crosstalk between tumour cells and TAMs in the local tumour microenvironment that may contribute to disease progression in pancreatic cancer patients with hyperglycaemia and T2D.

Topics: CD11c Antigen; Cell Line, Tumor; Coculture Techniques; Diabetes Mellitus, Type 2; Female; Glucose; Humans; Hyperglycemia; Hypoglycemic Agents; Interleukin-6; Interleukin-8; Lectins, C-Type; Macrophages; Male; Mannose Receptor; Mannose-Binding Lectins; Metformin; Neoplasm Invasiveness; Pancreatic Neoplasms; Receptors, Cell Surface

Chronic low-grade systemic inflammation presented in Type 2 diabetes mellitus plays a major role in disease progression as well as development of micro- and macro-vascular complications of diabetes. Therefore, reducing inflammation can be beneficial in prevention of diabetes complications.. To investigate the association between insulin resistance and inflammatory markers, and assessing the effects of oral Calcitriol on inflammatory cytokines in type 2 diabetic patients.. In this double-blind randomized placebo-controlled trial, 70 participants with type-2 diabetes were randomly divided to two groups. One group received two capsules of Calcitriol (0.25 μg 1,25-dihydroxy cholecalciferol per each capsule) per day. The second group received placebo tablets. At the beginning of the study, we assessed insulin resistance and its relation to inflammatory profile. Serum high sensitive C-reactive protein (hs CRP), interleukin-6 and interleukin-18 were also measured at the beginning and the end of the 12-week supplementation trial.. Mean calcium, phosphorus and vitamin D concentrations in the study participants were 8.98 ± 0.79 mg/dL, 3.86 ± 0.50 mg/dL and 40.91 ± 30.9 ng/mL, respectively. IL-18 and hsCRP had significant positive associations with insulin resistance markers and negative associations with insulin sensitivity markers. At the end of the 12-week supplementation trial, no significant difference was seen in serum levels of hsCRP, IL-6 and IL-18 between the two groups, while these values were adjusted for baseline values.. Inflammation was associated with insulin resistance in diabetic patients. No anti-inflammatory effect of Calcitriol in terms of decreasing hsCRP, IL-6 and IL-18 detected.

Topics: Adult; Aged; C-Reactive Protein; Calcitriol; Calcium; Calcium Channel Agonists; Diabetes Mellitus, Type 2; Female; Humans; Insulin Resistance; Interleukin-6; Interleukin-8; Male; Middle Aged; Treatment Outcome; Vitamin D

We performed this study to examine the metabolic differences arising from higher liver fat accumulation in obese Hispanic adolescents, with a particular focus on circulating levels of adipocytokines and insulin resistance.. Forty-one obese Hispanic adolescents (15.3 ± 1.0 years, body mass index percentile: 97.0 ± 3.9) were assessed for: visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT) and hepatic fat fraction (HFF) by magnetic resonance imaging; fasting measures of serum glucose, insulin and adipocytokines; homeostasis model assessment of insulin resistance (HOMA-IR); and insulin sensitivity (SI) and the acute insulin response to glucose (AIR) by intravenous glucose tolerance test. Subjects with normal levels of HFF (below 5%; n = 25) were compared to those with HFF > 5% (n = 16).. The two groups differing in HFF were similar for total body fat, VAT and SAT. The group with HFF > 5% had significantly (P < 0.05) higher interleukin-8 (IL-8) (6.1 ± 1.6 vs. 3.2 ± 0.4 pg mL(-1) ), NGF (30.2 ± 9.9 vs. 13.9 ± 1.6 pg mL(-1) ), HOMA-IR (8.8 ± 1.1 vs. 5.5 ± 0.5), AIR (1869 ± 206 vs. 1092 ± 165) and a tendency for lower SI (1.2 ± 0.4 vs. 2.1 ± 0.3; P = 0.06), with no significant differences in any of other factors measured.. These data suggest that elevated liver fat is most closely associated with elevated serum IL-8 and NGF levels as well as increased AIR and HOMA-IR. These elevated factors may play significant roles in the metabolic abnormalities associated with elevated liver fat in obese Hispanics.

Topics: Adipokines; Adolescent; Blood Glucose; Body Composition; California; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Fatty Liver; Female; Glucose Tolerance Test; Hispanic or Latino; Humans; Inflammation; Insulin; Insulin Resistance; Interleukin-8; Male; Nerve Growth Factor; Non-alcoholic Fatty Liver Disease; Obesity; Patient Education as Topic

Chromium and cysteine supplementation have been shown to improve glucose metabolism in animal studies. This study examined the hypothesis that chromium dinicocysteinate (CDNC), a complex of chromium and l-cysteine, is beneficial in lowering oxidative stress, vascular inflammation, and glycemia in type 2 diabetic subjects.. Type 2 diabetic subjects enrolled in this study were given placebo for 1 month for stabilization and then randomized into one of three groups: placebo (P), chromium picolinate (CP), or CDNC, after which they received daily oral supplementation for 3 months. Of the 100 patients enrolled in the study, 74 patients completed it. There were 25 patients in the P supplemented group, 25 in the CP supplemented and 24 in the CDNC supplemented group who completed the study. Blood markers of glycemia, vascular inflammation, HOMA insulin resistance, and oxidative stress were determined at randomization and after 3 months of supplementation with P, CP, or CDNC. There was a significant decrease at 3 months in insulin resistance (p = 0.02) and in the levels of protein oxidation (p = 0.02) and TNF-α (p = 0.01) in the CDNC supplemented cohort compared to baseline. However, there was no statistically significant change in these markers in the CP supplemented group compared to baseline. Insulin levels significantly decreased (p = 0.01) for subjects receiving CDNC but not CP. There was no significant impact of supplementation on HbA(1c) or glucose levels in either of the groups.. CDNC supplementation lowers insulin resistance by reducing blood levels of TNF-α, insulin, and oxidative stress in type 2 diabetic subjects. Therefore, CDNC supplementation has potential as an adjunct therapy for individuals with type 2 diabetes.

Topics: Adult; Cysteine; Diabetes Mellitus, Type 2; Dietary Supplements; Double-Blind Method; Female; Humans; Insulin; Insulin Resistance; Intercellular Adhesion Molecule-1; Interleukin-6; Interleukin-8; Male; Middle Aged; Organometallic Compounds; Oxidative Stress; Tumor Necrosis Factor-alpha

An imbalance between pro- and anti-inflammatory cytokine productions in adipose tissue is thought to contribute to chronic, systemic, low-grade inflammation and consequently to an increased risk of cardiovascular complications in obese and type 2 diabetic patients. Nonesterified fatty acids (NEFA), whose serum levels are elevated in such patients, have been shown to interfere with cytokine production in vitro. In order to evaluate the effects of elevated NEFA levels on cytokine production in adipose tissue in vivo we used an 18-gauge open-flow microperfusion (OFM) catheter to induce local inflammation in the subcutaneous adipose tissue (SAT) of healthy volunteers and to sample interstitial fluid (IF) specifically from the inflamed tissue. In two crossover studies, nine subjects received either an intravenous lipid-heparin infusion to elevate circulating NEFA levels or saline over a period of 28 h. The former increased the circulating levels of triglycerides (TGs), NEFA, glucose, and insulin over the study period. NEFA effects on locally induced inflammation were estimated by measuring the levels of a panel adipokines in the OFM probe effluent. Interleukin-6 (IL-6), IL-8, tumor necrosis factor-α (TNF-α) and monocyte chemoattractant protein-1 (MCP-1) levels increased during the study period but were not affected by lipid-heparin infusion. In contrast, the level of IL-10, an anti-inflammatory cytokine, was significantly reduced during the final hour of lipid-heparin infusion (saline: 449.2 ± 105.9 vs. lipid-heparin: 65.4 ± 15.4 pg/ml; P = 0.02). These data provide the first in vivo evidence that elevated NEFA can modulate cytokine production by adipose tissue.

Topics: Adipokines; Adult; Blood Glucose; Catheters; Chemokine CCL2; Cross-Over Studies; Cytokines; Diabetes Mellitus, Type 2; Fatty Acids, Nonesterified; Heparin; Humans; Inflammation; Insulin; Interleukin-10; Interleukin-6; Interleukin-8; Lipids; Male; Obesity; Retrospective Studies; Subcutaneous Fat; Triglycerides; Tumor Necrosis Factor-alpha; Young Adult

End-stage renal disease (ESRD) due to type 2 diabetic nephropathy is a very common condition which is increasing in prevalence, and is associated with high global levels of mortality and morbidity. Both proteinuria and transforming growth factor-β (TGF-β) may contribute to the development of ESRD in patients with diabetic nephropathy. Experimental studies indicate that turmeric improves diabetic nephropathy by suppressing TGF-β. Therefore, this study investigated the effects of turmeric on serum and urinary TGF-β, interleukin-8 (IL-8) and tumour necrosis factor-α (TNF-α), as well as proteinuria, in patients with overt type 2 diabetic nephropathy.. A randomized, double-blind and placebo-controlled study was carried out in the Diabetes Clinic of the Outpatient Department of Shiraz University of Medical Sciences on 40 patients with overt type 2 diabetic nephropathy, randomized into a trial group (n = 20) and a control group (n = 20). Each patient in the trial group received one capsule with each meal containing 500 mg turmeric, of which 22.1 mg was the active ingredient curcumin (three capsules daily) for 2 months. The control group received three capsules identical in colour and size containing starch for the same 2 months.. Serum levels of TGF-β and IL-8 and urinary protein excretion and IL-8 decreased significantly comparing the pre- and post-turmeric supplementation values. No adverse effects related to turmeric supplementation were observed during the trial.. Short-term turmeric supplementation can attenuate proteinuria, TGF-β and IL-8 in patients with overt type 2 diabetic nephropathy and can be administered as a safe adjuvant therapy for these patients.

Topics: Administration, Oral; Curcuma; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Dietary Supplements; Double-Blind Method; Female; Humans; Interleukin-8; Male; Middle Aged; Phytotherapy; Proteinuria; Transforming Growth Factor beta; Tumor Necrosis Factor-alpha

In view of the previously described anti-inflammatory effects of insulin, we investigated the potential suppressive effect of insulin on plasma concentrations and expression of the chemokines, monocyte chemoattractant protein-1 (MCP-1) and regulated on activation normal T-cell expressed and secreted (RANTES) and their receptors, chemokine receptor (CCR)-2 and CCR-5, in mononuclear cells (MNCs). We also investigated the effect of insulin on other chemokines.. Ten obese type 2 diabetic patients were infused with insulin (2 units/h with 100 ml of 5% dextrose/h) for 4 h. Another 8 and 6 type 2 diabetic patients were infused with 100 ml of 5% dextrose/h or saline for 4 h, respectively, and served as control subjects. Blood samples were obtained at 0, 2, 4, and 6 h.. Insulin infusion significantly suppressed the plasma concentrations of MCP-1, eotaxin, and RANTES and the expression of RANTES, macrophage inflammatory protein (MIP)-1beta, CCR-2, and CCR-5 in MNCs at 2 and 4 h. Dextrose and saline infusions did not alter these indexes.. A low-dose infusion of insulin suppresses the plasma concentration of key chemokines, MCP-1, and RANTES, and the expression of their respective receptors, CCR-2 and CCR-5, in MNCs. Insulin also suppresses the expression of RANTES and MIP-1beta in MNCs. These actions probably contribute to the comprehensive anti-inflammatory effect of insulin.

Topics: Adult; Blood Glucose; Chemokine CCL11; Chemokine CCL4; Chemokine CCL5; Chemokine CX3CL1; Chemokine CXCL12; Chemokines; CX3C Chemokine Receptor 1; Diabetes Mellitus, Type 2; Gene Expression; Humans; Hypoglycemic Agents; Immunosuppressive Agents; Inflammation; Infusions, Intravenous; Insulin; Interleukin-8; Middle Aged; Obesity; Receptors, CCR2; Receptors, CCR5; Receptors, Chemokine; Receptors, CXCR4

We investigated changes in serum biomarkers of vascular function after short-term, continuous sildenafil dosing in men with type 2 diabetes with erectile dysfunction.. Men with erectile dysfunction associated with type 2 diabetes mellitus were randomized to receive continuous, daily sildenafil (50 mg for 1 week run-in and 100 mg for 3 weeks) (148), or placebo (144) for 4 weeks (phase I) and then sildenafil (25, 50 or 100 mg) on demand for 12 weeks (phase II). Blood draws at baseline and after phases I and II were analyzed for cyclic guanosine monophosphate (endothelial function marker), 8-isoprostane (oxidative stress marker), and interleukin-6 and interleukin-8 (inflammatory cytokines). Primary and secondary erectile function outcome variables were affirmative responses on Sexual Encounter Profile question 3 (ability to maintain erection sufficient for sexual intercourse) and Erection Hardness Score, respectively.. Serum cyclic guanosine monophosphate levels were increased in the sildenafil group relative to the placebo group at 4 (p <0.01) and 16 (p <0.05) weeks, correlating with affirmative responses to Sexual Encounter Profile question 3 at the 4-week interval only (p <0.05). Serum 8-isoprostane levels were decreased to a nonsignificant degree in the sildenafil group at 4 weeks with no further change at 16 weeks, whereas interleukin-6 and interleukin-8 levels were unchanged at either interval, and these levels were unassociated with erectile function outcomes.. These data suggest that short-term, continuous sildenafil treatment causes systemic endothelial function to be enhanced and remain so for a duration after its discontinuation. However, they do not indicate any influence of this treatment on systemic oxidative stress or inflammation, or an effect on long-term erectile function improvement.

Topics: Adult; Aged; Biomarkers; Cyclic GMP; Diabetes Complications; Diabetes Mellitus, Type 2; Dinoprost; Endothelium, Vascular; Erectile Dysfunction; Humans; Interleukin-6; Interleukin-8; Male; Middle Aged; Oxidative Stress; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones; Treatment Outcome

A single high-fat meal induces endothelial activation, which is associated with increased serum concentrations of inflammatory cytokines.. We compared the effect of 3 different meals on circulating concentrations of interleukin 8 (IL-8), interleukin 18 (IL-18), and adiponectin in healthy subjects and in patients with type 2 diabetes mellitus.. Thirty patients with newly diagnosed type 2 diabetes and 30 matched, nondiabetic subjects received the following 3 isoenergetic (780 kcal) meals separated by 1-wk intervals: a high-fat meal; a high-carbohydrate, low-fiber (4.5 g) meal; and a high-carbohydrate, high-fiber meal in which refined-wheat flour was replaced with whole-wheat flour (16.8 g). We analyzed serum glucose and lipid variables and serum IL-8, IL-18, and adiponectin concentrations at baseline and at 2 and 4 h after ingestion of the meals.. Compared with nondiabetic subjects, diabetic patients had higher fasting IL-8 (P < 0.05) and IL-18 (P < 0.01) concentrations and lower adiponectin concentrations (P < 0.01) at baseline. In both nondiabetic and diabetic subjects, IL-18 concentrations increased and adiponectin concentrations decreased (P < 0.05) from baseline concentrations after consumption of the high-fat meal. After consumption of the high-carbohydrate, high-fiber meal, serum IL-18 concentrations decreased from baseline concentrations (P < 0.05) in both nondiabetic and diabetic subjects; adiponectin concentrations decreased after the high-carbohydrate, low-fiber meal in diabetic patients. IL-8 concentrations did not change significantly after consumption of any of the 3 meals.. This study provides evidence that circulating IL-18 and adiponectin concentrations are modulated by familiar foodstuffs in humans. Meal modulation of cytokines involved in atherogenesis may represent a safe strategy for ameliorating atherogenetic inflammatory activity in diabetic patients.

Topics: Adiponectin; Adult; Blood Glucose; Coronary Artery Disease; Cross-Over Studies; Diabetes Mellitus, Type 2; Dietary Carbohydrates; Dietary Fats; Dietary Fiber; Female; Humans; Intercellular Signaling Peptides and Proteins; Interleukin-18; Interleukin-8; Male; Proteins

To evaluate changes in ocular surface indices and tear cytokines after cataract surgery in type 2 diabetic patients.. Ocular surface indices and concentrations of tear cytokines (MCP-1, IL-6, IL-8, and VEGF) were evaluated at baseline and one week and one month postoperatively.. Patients (30 diabetic and 30 control) were enrolled. In the diabetic group, changes in ocular symptom and tear breakup time remained until one month postoperatively (. Diabetic patients can experience more prominent changes after surgery and these changes were accompanied by an increase of several tear cytokines.

Topics: Cataract; Cornea; Cytokines; Diabetes Mellitus, Type 2; Humans; Interleukin-8

Type 2 diabetes (T2D) is known to be associated with chronic inflammation, but the inflammatory regulators/markers are not exactly defined and the link between them remains undetermined. The objective of this study is to identify these markers by testing traditional (IL6 & IL8) and non-traditional (TREM1 & uPAR) inflammatory markers.. Data and blood samples were obtained from 114 T2D and 74 non-diabetic Kuwaiti subjects attending health facilities in Kuwait. Chemical analyzers were used to measure glycemic and lipid profiles, while ELISA was used to measure plasma levels of insulin and several inflammatory markers.. Showed that the IL-6 and TREM1 were significantly higher in T2D compared to non-diabetic controls, and the uPAR level was borderline higher in T2D but significantly correlated with IL-6 levels. Unexpectedly, IL8 was significantly below normal in T2D and IL6/IL8 ratio was significantly higher in T2D patients. Unlike other tested markers, uPAR was in addition strongly correlated with insulin levels and HOMA-IR index.. Raised levels of IL6, TREMI, IL6/IL8 ratio, and the strong positive correlation of plasma levels of uPAR with IL-6, insulin, and HOMA-IR index, are reliable spectators of chronic inflammation in T2D patients. The reduced level of IL-8 in T2D was a peculiar observation that needs further explanation. Finally, the consequences and impact of the sustained rise of these inflammatory regulators in diabetic tissues need to be meticulously explored.

Topics: Biomarkers; Diabetes Mellitus, Type 2; Humans; Inflammation; Insulin; Insulin Resistance; Interleukin-6; Interleukin-8; Interleukins; Receptors, Urokinase Plasminogen Activator; Triggering Receptor Expressed on Myeloid Cells-1

Diabetes mellitus is a metabolic disease, which genetic and environmental factors play a role in its pathogenesis. Cytokines as important elements in the immune system have diverse expressions in different individuals and societies and are effective in the pathogenesis of diabetes. This study investigated the relationship between blood sugar control and salivary levels of interleukin-8 (IL-8) in patients with type 2 diabetes.. This cross-sectional study was conducted on 73 subjects (35 diabetic and 38 healthy individuals). Unstimulated saliva samples were collected and the correlation between IL-8, as an inflammatory marker and HbA1c (Haemoglobin A1C) was studied.. The levels of IL-8 and HbA1c were significantly higher in the patient group than control group (p < .001, p < .001, respectively). There was not any relationship between salivary IL-8 levels and glycemic control levels (p = .629). Also, there was no remarkable difference between men and women in terms of the levels of IL-8 and HbA1c saliva (p = .524, p = .998, respectively).. Although the salivary IL-8 levels were higher in the diabetic patients, blood sugar control did not significantly affect cytokine concentrations. Increased salivary levels of IL-8 in patients with type 2 diabetes could be a basis for risk assessment, prevention and treatment of diabetes-related complications.

Topics: Blood Glucose; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Interleukin-8; Male

COVID-19 mortality is increased in patients with diabetes. A common hypothesis is that the relationship of inflammation with COVID-19 mortality differs by diabetes status.. The aim of this study was to determine the relationship of inflammation with mortality in COVID-19 hospitalized patients and to assess if the relationship differs by strata of type 2 diabetes status.. A case-control (died-survived) study of 538 COVID-19 hospitalized patients, stratified by diabetes status, was conducted at Columbia University Irving Medical Center. We quantified the levels of 8 cytokines and chemokines in serum, including interferon (IFN)-α2, IFN-γ, interleukin (IL)-1α, IL-1β, IL-6, IL-8/CXCL8, IFNγ-induced protein 10 (IP10)/CXCL10 and tumor necrosis factor α (TNF-α) using immunoassays. Logistic regression models were used to model the relationships of log-transformed inflammatory markers (or their principal components) and mortality.. In multiple logistic regression models, higher serum levels of IL-6 (adjusted odds ratio [aOR]:1.74, 95% CI [1.48, 2.06]), IL-8 (aOR: 1.75 [1.41, 2.19]) and IP10 (aOR: 1.36 [1.24, 1.51]), were significantly associated with mortality. This association was also seen in second principal component with loadings reflecting similarities among these 3 markers (aOR: 1.88 [1.54-2.31]). Significant positive association of these same inflammatory markers with mortality was also observed within each strata of diabetes.. We show that mortality in COVID-19 patients is associated with elevated serum levels of innate inflammatory cytokine IL-6 and inflammatory chemokines IL-8 and IP10. This relationship is consistent across strata of diabetes, suggesting interventions targeting these innate immune pathways could potentially also benefit patients with diabetes.

Topics: Biomarkers; Chemokine CXCL10; COVID-19; Cytokines; Diabetes Mellitus, Type 2; Humans; Inflammation; Interleukin-6; Interleukin-8; SARS-CoV-2

Type 2 Diabetes (T2D) is associated with impaired vascularization of adipose tissue (AT) . IL8, GROα and IL15 are pro-angiogenic myokines, secreted at elevated levels by T2D myotubes. We explored the direct impact of these myokines on AT vascularization. AT explants from subjects with T2D and without diabetes (non-diabetic, ND) were treated with rIL8, rGROα and rIL15 in concentrations equal to those in conditioned media (CM) from T2D and ND myotubes, and sprout formation evaluated. Endothelial cells (EC) were isolated from T2D and ND-AT, treated with rGROα and tube formation evaluated. Finally, we investigated the involvement of MMP-2 and -9 in vascularization. ND and T2D concentrations of IL8 or IL15   caused similar stimulation of sprout formation in ND- and T2D-AT. GROα exerted a similar effect in ND-AT. When T2D-AT explants were exposed to GROα, sprout formation in response to T2D concentrations was reduced compared to ND. Exposure of EC from T2D-AT to GROα at T2D concentrations resulted in reduced tube formation. Reduced responses to GROα in T2D-AT and EC were also seen for secretion of MMP-2 and -9. The data indicate that skeletal muscle can potentially regulate AT vascularization, with T2D-AT having impairments in sensitivity to GROα, while responding normally to IL8 and IL15.

Topics: Adipose Tissue; Chemokine CXCL1; Diabetes Mellitus, Type 2; Endothelial Cells; Humans; Interleukin-15; Interleukin-8; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9

Advanced glycation end products (AGEs) and the cognate receptor, named RAGE, are involved in metabolic disorders characterized by hyperglycemia, type 2 diabetes mellitus (T2DM) and obesity. Moreover, the AGEs/RAGE transduction pathway prompts a dysfunctional interaction between breast cancer cells and tumor stroma toward the acquisition of malignant features. However, the action of the AGEs/RAGE axis in the main players of the tumor microenvironment, named breast cancer-associated fibroblasts (CAFs), remains to be fully explored. In the present study, by chemokine array, we first assessed that interleukin-8 (IL-8) is the most up-regulated pro-inflammatory chemokine upon AGEs/RAGE activation in primary CAFs, obtained from breast tumors. Thereafter, we ascertained that the AGEs/RAGE signaling promotes a network cascade in CAFs, leading to the c-Fos-dependent regulation of IL-8. Next, using a conditioned medium from AGEs-exposed CAFs, we determined that IL-8/CXCR1/2 paracrine activation induces the acquisition of migratory and invasive features in MDA-MB-231 breast cancer cells. Altogether, our data provide new insights on the involvement of IL-8 in the AGEs/RAGE transduction pathway among the intricate connections linking breast cancer cells to the surrounding stroma. Hence, our findings may pave the way for further investigations to define the role of IL-8 as useful target for the better management of breast cancer patients exhibiting metabolic disorders.

Topics: Breast Neoplasms; Cancer-Associated Fibroblasts; Diabetes Mellitus, Type 2; Female; Humans; Interleukin-8; Signal Transduction; Tumor Microenvironment

Inflammation is a prominent clinical manifestation in type 2 diabetes mellitus (T. The present study has been designed to check the serum levels of PAR-1 and correlate with various clinical manifestations and inflammatory cytokines levels in type 2 diabetic subjects.. The study population was divided into two groups, healthy volunteers (n = 15): normal glycated hemoglobin (HbA1c) (4.26 ± 0.55) and type 2 diabetic subjects (n = 30): HbA1c levels (7.80 ± 2.41). The serum levels of PAR-1 (ELISA method) were studied in both groups and correlated with demographic parameters age, weight, body mass index (BMI), and conventional inflammation biomarkers like C-reactive protein (CRP), interleukin 6 (IL-6), interleukin 8 (IL-8), and tumour necrosis factor-alpha (TNF-α).. The demographic variables including the body weight (77.38 ± 10.00 vs. controls 55.26 ± 6.99), BMI (29.39 ± 3.61 vs. controls 25.25 ± 4.01), glycemic index HbA1c (7.80 ± 2.41 vs. controls 4.26 ± 0.55) were found to be statistically increased in T. Our findings indicate that the elevated serum PAR-1 levels serve as an independent predictor of inflammation in T

Topics: Biomarkers; Blood Glucose; Body Weight; C-Reactive Protein; Cytokines; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Inflammation; Interleukin-6; Interleukin-8; Receptor, PAR-1; Tumor Necrosis Factor-alpha

Low vitamin D concentrations are associated with metabolic derangements, notably insulin resistance and pancreatic beta-cell dysfunction in Caucasian populations. Studies on its association with the clinical, metabolic, and immunologic characteristics in black African adult populations with new-onset diabetes are limited. This study aimed to describe the clinical, metabolic, and immunologic characteristics of a black Ugandan adult population with recently diagnosed diabetes and hypovitaminosis D.. Serum vitamin D concentrations were measured in 327 participants with recently diagnosed diabetes. Vitamin D deficiency, vitamin D insufficiency, and normal vitamin D status were defined as serum 25 hydroxyvitamin D levels of < 20 ng/ml, 21-29 ng/ml, and ≥ 30 ng/ml, respectively.. The median (IQR) age, glycated haemoglobin, and serum vitamin D concentration of the participants were 48 years (39-58), 11% (8-13) or 96 mmol/mol (67-115), and 24 ng/ml (18-30), respectively. Vitamin D deficiency, vitamin D insufficiency, and normal vitamin D status were noted in 105 participants (32.1%), 140 participants (42.8%), and 82 participants (25.1%), respectively. Compared with those having normal serum vitamin D levels, participants with vitamin D deficiency and insufficiency had higher circulating concentrations of interleukin (IL) 6 (29 [16-45] pg/ml, 23 [14-40] pg/ml vs 18 [14-32] pg/ml, p = 0.01), and IL-8 (24 [86-655] pg/ml, 207 [81-853] pg/ml vs 98 [67-224], p = 0.03). No statistically significant differences were noted in the markers of body adiposity, insulin resistance, and pancreatic beta-cell function between both groups.. Vitamin D deficiency and insufficiency were highly prevalent in our study population and were associated with increased circulating concentrations of pro-inflammatory cytokines. The absence of an association between pancreatic beta-cell function, insulin resistance, and low vitamin D status may indicate that the latter does not play a significant role in the pathogenesis of type 2 diabetes in our adult Ugandan population.

Topics: Adult; Cytokines; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Insulin Resistance; Interleukin-8; Middle Aged; Uganda; Vitamin D; Vitamin D Deficiency; Vitamins

The aim of this study was to determine the Firmicutes/Bacteroidetes ratio in the gut microbiota and IL-1β, IL-6, IL-8, TLR2, TLR4 and TLR5 gene expression levels in the blood of adult type 2 diabetes (T2D) patients and compare it with that of adult nondiabetic healthy controls (HC).. Between May 2016 and April 2017, 99 T2D patients and 99 HCs were enrolled in the study. Bacteroidetes and Firmicutes levels were assessed from stool sample DNA and IL-1β, IL-6, IL-8, TLR2, TLR4, and TLR5 gene expression levels assesed from blood sample RNA via qPCR from both T2D patients and healthy controls.. The Firmicutes/Bacteroidetes ratio detected in the stool of type 2 diabetes patients was found to be higher with a statistically significant difference (p < 0.0001). Gene expression levels of IL-1β, IL-6, IL-8, TLR2, TLR4, and TLR5 were found to be upregulated.. The highest upregulation was detected in IL-6 with 11 fold in T2D patients comparing with HCs. F/B ratio and gene expression levels were elevated in T2D patients. Firmicutes were positively correlated with studied gene expressions. A better understanding of the complex interaction between gut microbiota, environment, and diabetes will allow for more effective prevention and treatment strategies for T2D.

Topics: Adult; Bacteroidetes; Diabetes Mellitus, Type 2; Firmicutes; Gastrointestinal Microbiome; Gene Expression; Humans; Interleukin-1beta; Interleukin-6; Interleukin-8; RNA; Toll-Like Receptor 2; Toll-Like Receptor 4; Toll-Like Receptor 5

Sleep apnoea syndrome is characterized by recurrent episodes of oxygen desaturation and reoxygenation (intermittent hypoxia [IH]) and is a risk factor for insulin resistance/Type 2 diabetes. The induction of insulin resistance in skeletal muscle is a key phenomenon to develop diabetes. However, the mechanisms linking IH stress and insulin resistance remain elusive. We exposed human RD and mouse C2C12 muscle cells to normoxia or IH and measured their mRNA levels by real-time RT-PCR. We found that IH significantly increased the mRNA and protein levels of muscle-derived insulin resistance-factors (myokines) such as IL-8, osteonectin (ON), and myonectin (MN) in muscle cells. We further analysed the IH-induced expression mechanisms of IL-8, ON, and MN genes in muscle cells. Deletion analyses of the human myokine promoter(s) revealed that the regions -152 to -151 in IL-8, -105 to -99 in ON, and - 3741 to -3738 in MN promoters were responsible for the activation by IH in RD cells. The promoters contain consensus transcription factor binding sequences for OCT1 in IL-8 and MN promoters, and for NRF2 in ON promoter, respectively. The introduction of siRNA for OCT1 abolished the IH-induced expression(s) of IL-8 and MN and siRNA for NRF2 abolished the IH-induced expression of ON.

Topics: Animals; Diabetes Mellitus, Type 2; Humans; Hypoxia; Insulin Resistance; Interleukin-8; Mice; Muscle Fibers, Skeletal; NF-E2-Related Factor 2; Osteonectin; RNA, Messenger; RNA, Small Interfering; Up-Regulation

Was to analyze the effectiveness of therapeutic and preventive measures aimed at reducing hyperesthesia of hard dental tissues in patients with background somatic diseases.. The study involved 113 patients with increased tooth sensitivity and treated in the gastroenterological and endocrinological departments of the S.M. Kirov City Clinical Hospital No.3» in Astrakhan in the period from 2018 to 2021 at the age of 26-43 years. The main group included 52 patients with confirmed diagnoses of gastric and duodenal ulcer, pancreatitis and type II diabetes mellitus who were treated for dental hyperesthesia with an integrated approach. The control group included 61 patients with periodontal disease without background somatic pathologies in whom hyperesthesia was treated by remineralizing therapy. The effectiveness of the treatment was determined in dynamics on the 10th and 40th days of treatment using OHI-S, PMA indices, dental hypersensitivity prevalence (DHP), dental hypersensitivity intensity (DHI), Dental Sensitivity Index (DSI), Efficacy of Dental Sensitivity Index (EDSI). In addition, the pH of saliva, the activity of lysozyme and S-IgA, and the levels of cytokines IL-1β, IL-4, IL-6, and IL-8 were determined.. The average value of OHI-S in the main group on the 10th day of treatment decreased from 2.25±0.12 (poor level of hygiene) to 1.47±0.09 (satisfactory level). The PMA index in the main group also tended to decrease from 32.1±1.44% (moderate degree of gingivitis) to 20.5±2.08% (mild degree) on the 10th day of treatment. The average values of DPH, DPI, EDSI and DSI in the main group had a noticeable decrease already on the 10th day from the start of treatment (from 12.3±1.66% to 2.1±1.22%; from 2.5±0.48 to 1.2±0.16; from 48.3±1.14% to 40.8±1.71%; from 42.1±2.07% to 20.8±1, 65% respectively). In the main group on the 10th and 40th day of treatment the pH values of non-stimulated and stimulated saliva stabilized (from 4.61±0.12 to 6.94±0.07 and from 5.47±0.21 to 7.42±0.24, respectively), the activity of lysozyme increased (from 45.97±1.46% to 55.19±0.96%) alongside with secretory IgA (from 0.17±0.02 to 0.33±0.21 mg/ml). Also, indicators of cytokines IL-1β, IL-4, IL-6, IL-8 tended to improve. The analysis of the control group revealed persistent mean values that did not yield to significant changes either in the course of treatment.. Thus, in patients of the main group, the results obtained indicate an improvement in the dental status and activation of cytokine regulation, providing a combination of active components of the mineral complex. In controls the method of remineralizing therapy for tooth hyperesthesia alleviated dental hypersensitivity, but without significant improvement of the laboratory results.. Проанализировать эффективность лечебно-профилактических мероприятий, направленных на снижение гиперестезии твердых тканей зубов, у пациентов с фоновыми соматическими заболеваниями.. В исследовании приняли участие 113 пациентов, имевшие повышенную чувствительность зубов и проходившие лечение в гастроэнтерологическом и эндокринологическом отделениях «Городская клиническая больница №3 им. С.М. Кирова» г. Астрахани в период с 2018 по 2021 г. в возрасте 26—43 лет. В основную группу вошли 52 пациента с язвенной болезнью желудка и двенадцатиперстной кишки, панкреатитом или сахарным диабетом II типа, которым проводилось лечение гиперестезии зубов с применением комплексного подхода. В контрольную группу вошел 61 пациент с заболеваниями пародонта без фоновых соматических патологий, у которых лечение гиперестезии проводилось методом реминерализирующей терапии. Эффективность лечения определяли в динамике на 10-й и 40-й дни лечения с помощью индексов гигиены OHI-S, папиллярно-маргинально-альвеолярного индекса РМА в модификации Parma, индексов распространенности гиперестезии зубов (ИРГЗ), интенсивности гиперестезии зубов (ИИГЗ), сенситивности зубов (ИСЗ О-У), эффективности сенситивности зубов (СЗ). Помимо этого определяли pH слюны, активность лизоцима и S-IgA, уровни цитокинов ИЛ-1β, ИЛ-4, ИЛ-6, ИЛ-8.. Показатели индекса OHI-S в основной группе уже на 10-й день лечения снизились с 2,25±0,12 (неудовлетворительный уровень гигиены) до 1,47±0,09 (удовлетворительный уровень). Показатели индекса PMA в основной группе также имели тенденцию к снижению с 32,1±1,44% (средняя степень гингивита) до 20,5±2,08% (легкая степень) на 10-й день лечения. Средние значения показателей индексов ИРГЗ, ИИГЗ, СЗ, ИСЗ О-У в основной группе заметно снизились уже на 10-й день от начала лечения (с 12,3±1,66% до 2,1±1,22%; с 2,5±0,48 до 1,2±0,16; с 48,3±1,14% до 40,8±1,71%; с 42,1±2,07% до 20,8±1,65% соответственно). В основной группе у пациентов на 10-й и далее на 40-й день лечения наблюдалось улучшение показателя pH нестимулированной и стимулированной слюны (с 4,61±0,12 до 6,94±0,07 и с 5,47±0,21 до 7,42±0,24 соответственно), возросли показатели активность лизоцима (с 45,97±1,46% до 55,19±0,96%) вместе с показателями секреторного IgA (с 0,17±0,02 до 0,33±0,21 мг/мл). Также улучшились показатели цитокинов ИЛ-1β, ИЛ-4, ИЛ-6, ИЛ-8. Анализ контрольной группы выявил стойкие средние показатели индексов, которые значительно не менялись в ходе лечения.. У пациентов основной группы полученные результаты свидетельствуют об улучшении стоматологического статуса и активации цитокиновой регуляции. У пациентов контрольной группы с помощью реминерализирующей терапии удалось нивелировать гиперчувствительность зубов, но лабораторные показатели корректировались незначительно.

Topics: Adult; Dentin Sensitivity; Diabetes Mellitus, Type 2; Humans; Interleukin-4; Interleukin-6; Interleukin-8; Muramidase; Saliva; Tooth Remineralization

The C-X-C motif chemokine ligand 10 (CXCL10) participates in diabetes and diabetic cardiomyopathy development from the early stages. Rosiglitazone (RGZ) exhibits anti-inflammatory properties and can target cardiomyocytes secreting CXCL10, under interferon (IFN)γ and tumor necrosis factor (TNF)α challenge. Cardiomyocyte remodeling, CD4 + T cells and dendritic cells (DCs) significantly contribute to the inflammatory milieu underlying and promoting disease development. We aimed to study the effect of RGZ onto inflammation-induced secretion of CXCL10, IFNγ, TNFα, interleukin (IL)-6 and IL-8 by human CD4 + T and DCs, and onto IFNγ/TNFα-dependent signaling in human cardiomyocytes associated with chemokine release.. Cells maintained within an inflammatory-like microenvironment were exposed to RGZ at near therapy dose (5 µM). ELISA quantified cytokine secretion; qPCR measured mRNA expression; Western blot analyzed protein expression and activation; immunofluorescent analysis detected intracellular IFNγ/TNFα-dependent trafficking.. In human CD4 + T cells and DCs, RGZ inhibited CXCL10 release likely with a transcriptional mechanism, and reduced TNFα only in CD4 + T cells. In human cardiomyocytes, RGZ impaired IFNγ/TNFα signal transduction, blocking the phosphorylation/nuclear translocation of signal transducer and activator of transcription 1 (Stat1) and nuclear factor-kB (NF-kB), in association with a significant decrease in CXCL10 expression, IL-6 and IL-8 release.. As the combination of Th1 biomarkers like CXCL10, IL-8, IL-6 with classical cardiovascular risk factors seems to improve the accuracy in predicting T2D and coronary events, future studies might be desirable to further investigate the anti-Th1 effect of RGZ.

Topics: Anti-Inflammatory Agents; Cells, Cultured; Diabetes Mellitus, Type 2; Diabetic Cardiomyopathies; Humans; Hypoglycemic Agents; Inflammation; Interferon-gamma; Interleukin-8; Myocytes, Cardiac; NF-kappa B; Prognosis; Rosiglitazone; T-Lymphocytes, Helper-Inducer; Thiazolidinediones; Tumor Necrosis Factor-alpha

Angiogenesis is a multistep process requiring endothelial cell activation, migration, proliferation and tube formation. We recently reported that elevated secretion of interlukin 8 (IL8) by myotubes (MT) from subjects with Type-2 Diabetes (T2D) reduced angiogenesis by human umbilical vein endothelial cells (HUVEC) and human skeletal muscle explants. This lower vascularization was mediated through impaired activation of the phosphatidylinositol 3-kinase (PI3K)-pathway. We sought to investigate additional signaling elements that might mediate reduced angiogenesis. HUVEC were exposed to levels of IL8 equal to those secreted by MT from non-diabetic (ND) and T2D subjects and the involvement of components in the angiogenic response pathway examined. Cellular content of reactive oxygen species and Nitrate secretion were similar after treatment with [ND-IL8] and [T2D-IL8]. CXCR1 protein was down-regulated after treatment with [T2D-IL8] (p < 0.01 vs [ND-IL8] treatment); CXCR2 expression was unaltered. Addition of neutralizing antibodies against CXCR1 and CXCR2 to HUVEC treated with IL8 confirmed that CXCR1 alone mediated the angiogenic response to IL8. A key modulator of angiogenesis is matrix metalloproteinase-2 (MMP2). MMP2 secretion was higher after treatment with [ND-IL8] vs [T2D-IL8] (p < 0.01). MMP2 inhibition reduced tube formation to greater extent with [ND-IL8] than with [T2D-IL8] (p < 0.005). The PI3K-pathway inhibitor LY294002 reduced IL8-induced MMP2 release. IL8 regulation of MMP2 release was CXCR1 dependent, as anti-CXCR1 significantly reduced MMP2 release (p < 0.05). These results suggest that high levels of IL8 secreted by T2D MT trigger reduced capillarization via lower activation of a CXCR1-PI3K pathway, followed by impaired release and activity of MMP2.

Topics: Cell Movement; Cell Proliferation; Cells, Cultured; Diabetes Mellitus, Type 2; Human Umbilical Vein Endothelial Cells; Humans; Interleukin-8; Matrix Metalloproteinase 2; Muscle Fibers, Skeletal; Muscle, Skeletal; Neovascularization, Pathologic; Phosphatidylinositol 3-Kinases; Reactive Oxygen Species; Receptors, Interleukin-8A; Signal Transduction

Inflammation has a major role in diabetic kidney disease. We thus investigated the role of the IL-8-CXCR1/2 axis in favoring kidney damage in diabetes.. Urinary IL-8 levels were measured in 1247 patients of the Joslin Kidney Study in type 2 diabetes (T2D). The expression of IL-8 and of its membrane receptors CXCR1/CXCR2 was quantified in kidney tissues in patients with T2D and in controls. The effect of CXCR1/2 blockade on diabetic kidney disease was evaluated in db/db mice.. IL-8 urinary levels were increased in patients with T2D and diabetic kidney disease, with the highest urinary IL-8 levels found in the patients with the largest decline in glomerular filtration rate, with an increased albumin/creatine ratio and the worst renal outcome. Moreover, glomerular IL-8 renal expression was increased in patients with T2D, as compared to controls. High glucose elicits abundant IL-8 secretion in cultured human immortalized podocytes in vitro. Finally, in diabetic db/db mice and in podocytes in vitro, CXCR1/2 blockade mitigated albuminuria, reduced mesangial expansion, decreased podocyte apoptosis and reduced DNA damage.. The IL-8- CXCR1/2 axis may have a role in diabetic kidney disease by inducing podocyte damage. Indeed, targeting the IL-8-CXCR1/2 axis may reduce the burden of diabetic kidney disease.

Topics: Adult; Animals; Case-Control Studies; Cells, Cultured; Cohort Studies; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Humans; Interleukin-8; Italy; Kidney; Mice; Mice, Inbred C57BL; Mice, Transgenic; Podocytes; Receptors, CXCR; Receptors, Interleukin-8A; Receptors, Interleukin-8B; Signal Transduction

To evaluate if there is a link between inflammation (expressed by inflammatory cytokines) and the early stage of diabetic kidney disease (DKD), as shown by markers of podocyte damage and proximal tubular (PT) dysfunction.. In this study were enrolled 117 type 2 DM patients (36-normoalbuminuria, 42-microalbuminuria, 39- macroalbuminuria), and 11 healthy subjects. Serum and urinary IL-1 alpha, IL-8, IL-18, urinary albumin:creatinine ratio (UACR), eGFR, biomarkers of podocyte damage (podocalyxin, synaptopodin, nephrin) and of PT dysfunction (KIM-1, NAG) were assessed.. Pro-inflammatory interleukins are associated with podocyte injury and PT dysfunction in early DKD. These could exert a key role in the pathogenesis of early DKD, before the development of albuminuria.

Topics: Aged; Albuminuria; Cytokines; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Humans; Inflammation; Interleukin-18; Interleukin-1alpha; Interleukin-8; Kidney Tubules, Proximal; Middle Aged; Podocytes

The aim: To assess of pro-inflammatory IL-8 and anti-inflammatory IL-10 serum concentration in patients with T2DM with intraabdominal postoperative abscesses in perioperative period.. Materials and methods: The 48 participants, aged 40 - 75 years, among them 24 males and 24 females. All patients were divided into groups: group 1 - 12 patients with T2DM and intra-abdominal postoperative abscesses, group 2 - 12 patients without T2DM but with intra-abdominal postoperative abscesses and 24 healthy individuals. The level of IL-8and IL-10 serum was determined on the day before surgery, on the 2-3rd and 5-7th day after surgery in patients with type 2 diabetes and intra-abdominal postoperative abscesses.. Results and conclusions: The trajectories of the level of interleukins in patients with type 2 Diabetes mellitus were different from the trajectories of their level in patients without diabetes, which indicates a special immune response to nosocomial infection and surgical trauma. The mechanism of changes in serum levels of IL-8 and IL-10 in patients with type 2 Diabetes mellitus and postoperative intra-abdominal abscesses should be further studied in future studies on the specific causative agent of nosocomial infection and the cytokine response to it.

Topics: Abdominal Abscess; Abscess; Adult; Aged; Diabetes Mellitus, Type 2; Female; Humans; Interleukin-10; Interleukin-8; Male; Middle Aged

The intracellular ROCK signaling pathway is an important modulator of blood pressure and of cardiovascular and renal remodeling when Rho-kinase activity is increased. Besides, in preclinical models of diabetes, ROCK activation has also a role in abnormal glucose metabolism as well as in subsequent vascular and myocardial dysfunction. In humans, there are a few data assessing ROCK activation in patients with type 2 diabetes mellitus (T2D) and no studies assessing upstream/downstream components of the ROCK pathway. We assessed here levels of ROCK activation and some of the RhoA/ROCK cascade molecules in peripheral blood mononuclear cells (PBMCs) in T2D patients under current treatment.. Cross-sectional observational study comparing 28 T2D patients under current antidiabetic treatment with 31 consecutive healthy subjects, matched by age and gender. Circulating levels of malondialdehyde, angiotensin II and inflammatory cytokines IL-6 and IL-8 were determined in all subjects. ROCK activation in PMBCs, upstream and downstream cascade proteins, and levels of the proinflammatory molecules VCAM, ICAM-1 and IL-8 were determined in their PMBCs by Western blot.. Compared to healthy controls, ROCK activation in T2D patients measured by 2 direct ROCK targets in PBMCs was increased by 420 and 570% (p < 0001) and it correlated significantly with serum glucose levels. p38 MAPK phosphorylation (downstream from ROCK) and JAK-2 (upstream from ROCK) were significantly higher in the T2D patients by 580% and 220%, respectively. In T2D patients, significantly increased PBMC levels of the proinflammatory molecules VCAM-1, ICAM-1 and IL-8 were observed compared to control subjects (by 180%, 360% and 260%, respectively). Circulating levels of Ang II and MDA were significantly higher in T2D patients by 29 and 63%, respectively.. T2D patients under treatment with glucose-lowering drugs, antihypertensive treatment as well as with statins have significantly increased ROCK activation in their circulating leukocytes along with higher phosphorylation of downstream cascade proteins despite pharmacologic treatment, along with increased plasma angiotensin II and MDA levels. ROCK inhibition might have an additional role in the prevention and treatment of T2D.

Topics: Aged; Angiotensin II; Antihypertensive Agents; Biomarkers; Case-Control Studies; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Enzyme Activation; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypoglycemic Agents; Intercellular Adhesion Molecule-1; Interleukin-8; Janus Kinase 2; Leukocytes, Mononuclear; Male; Malondialdehyde; Middle Aged; p38 Mitogen-Activated Protein Kinases; rho-Associated Kinases; Signal Transduction; Vascular Cell Adhesion Molecule-1

Type 2 diabetes mellitus (T2DM) is an important risk factor for development of tuberculosis (TB). Our previous study showed glibenclamide, an anti-diabetic drug used to control blood glucose concentration, reduced interleukin (IL)-8 secretion from primary human monocytes challenged with M. tuberculosis (Mtb). In mice infected with Mtb, IL-1β is essential for host resistance through the enhancement of cyclooxygenase that limits excessive Type I interferon (IFN) production and fosters Mtb containment. We hypothesize that glibenclamide may also interfere with monocyte mediated immune responses against Mtb and alter the balance between IL-1β and IFNα-mediated immunity. Purified monocytes from non-diabetic and diabetic individuals were infected with Mtb or M. bovis BCG. We demonstrate that monocytes from diabetes patients who were being treated with glibenclamide showed reduced IL-1β and IL-8 secretion when exposed to Mtb. Additionally, these responses also occurred when monocytes from non-diabetic individuals were pre-treated with glibenclamide in vitro. Moreover, this pre-treatment enhanced IFNa1 expression but was not involved with prostaglandin E2 (PGE2) expression in response to Mtb infection. Taken together, our data show that glibenclamide might exacerbate susceptibility of diabetes patients to Mtb infection by reducing IL-1β and IL-8 production by monocytes.

Topics: Adult; Aged; Case-Control Studies; Cells, Cultured; Diabetes Mellitus, Type 2; Dinoprostone; Female; Glyburide; Host-Pathogen Interactions; Humans; Hypoglycemic Agents; Interferon-alpha; Interleukin-1beta; Interleukin-8; Male; Middle Aged; Monocytes; Mycobacterium bovis; Mycobacterium tuberculosis; Risk Assessment; Tuberculosis

Interleukin-8 (IL-8, also named CXCL8) binds to its receptors (CXCR1 and CXCR2) with subsequent recruitment of neutrophils and enhancement of their infiltration into inflamed sites, which exaggerates inflammation in many diseases. Recent studies have proposed that metabolic disorders can be attenuated by counteracting certain inflammatory signal pathways. In this study, we examined whether intervention with G31P, an antagonist of CXCL8, could attenuate tissue inflammation and development of metabolic disorders in

Topics: Animals; Cytokines; Diabetes Mellitus, Type 2; Disease Models, Animal; Fatty Acids, Nonesterified; Gluconeogenesis; Insulin; Insulin Resistance; Interleukin-6; Interleukin-8; Lipid Metabolism; Liver; Macrophages; Mice; Peptide Fragments; Phosphorylation; Proto-Oncogene Proteins c-akt; Receptors, Interleukin-8A; Receptors, Interleukin-8B; Tumor Necrosis Factor-alpha

Diabetes mellitus, a metabolic disease characterized by hyperglycemia and poor glucose control, is a risk factor for

Topics: Adult; Aged; Case-Control Studies; Cell Survival; Diabetes Mellitus, Type 2; Female; Gene Expression; Glucose; Humans; Hyperglycemia; Interleukin-10; Interleukin-1beta; Interleukin-6; Interleukin-8; Lipopolysaccharide Receptors; Lipopolysaccharides; Lipoproteins; Male; Middle Aged; Monocytes; Mycobacterium tuberculosis; Primary Cell Culture; Toll-Like Receptor 2; Toll-Like Receptor 4; Tuberculosis, Pulmonary; Tumor Necrosis Factor-alpha

Evidence suggests that exercise improves neutrophil function. The decreased functional longevity of neutrophils and their increased clearance from infectious sites contribute to the increased susceptibility to infection and severity of infection observed in patients with diabetes.. Herein, we investigated the effects of a dance program on neutrophil number, function, and death in type 2 diabetes mellitus (T2DM) patients and healthy volunteers.. Ten patients with T2DM and twelve healthy individuals participated in a moderate-intensity dance training program for 4 months. The plasma levels of leptin, free fatty acids (FFAs), tumour necrosis factor-. Training reduced plasma levels of TNF-. Dance training is a nonpharmacological strategy to reduce inflammation and improve neutrophil clearance in patients with T2DM.

Topics: Dancing; Diabetes Mellitus, Type 2; Female; Humans; Interleukin-1beta; Interleukin-6; Interleukin-8; Middle Aged; Neutrophils; Tumor Necrosis Factor-alpha

Type 2 Diabetes (T2D) is strongly associated with obesity and inflammation. Toll-like receptor-4 (TLR-4) is the major pro-inflammatory pathway with its ligands and downstream products increased systemically in T2D and in at-risk individuals. Detailed mechanisms of the complex proinflammatory response in pancreatic islets remain unknown. In isolated human islets LPS induced IL-1β, IL-6, IL-8 and TNF production in a TLR4-dependent manner and severely impaired β-cell survival and function. IL-6 antagonism improved β-cell function. IL-8, which was identified specifically in α-cells, initiated monocyte migration, a process fully blocked by IL-8 neutralization. The TLR4 response was potentiated in obese donors; with higher IL-1β, IL-6 and IL-8 expression than in non-obese donors. TLR4 activation leads to a complex multi-cellular inflammatory response in human islets, which involves β-cell failure, cytokine production and macrophage recruitment to islets. In obesity, the amplified TLR4 response may potentiate β-cell damage and accelerate diabetes progression.

Topics: Apoptosis; Cell Movement; Chemokines; Cytokines; Diabetes Mellitus, Type 2; Disease Progression; Gene Expression Regulation; Humans; Inflammation; Insulin; Insulin Secretion; Insulin-Secreting Cells; Interleukin-1beta; Interleukin-6; Interleukin-8; Islets of Langerhans; Macrophages; Obesity; Toll-Like Receptor 4; Tumor Necrosis Factor-alpha

Glycation and the accumulation of advanced glycation end products (AGEs) are known to occur during normal aging but also in the progression of several diseases, such as diabetes. Diabetes type II and aging both lead to impaired wound healing. It has been demonstrated that macrophages play an important role in impaired wound healing, however, the underlying causes remain unknown. Elevated blood glucose levels as well as elevated methylglyoxal (MGO) levels in diabetic patients result in glycation and increase of AGEs. We used MGO to investigate the influence of glycation and AGEs on macrophages. We could show that glycation, but not treatment with AGE-modified serum proteins, increased expression of pro-inflammatory cytokines interleukin 1β (IL-1β) and IL-8 but also affected IL-10 and TNF-α expression, resulting in increased inflammation. At the same time, glycation reduced phagocytic efficiency and led to impaired clearance rates of invading microbes and cellular debris. Our data suggest that glycation contributes to changes of macrophage activity and cytokine expression and therefore could support the understanding of disturbed wound healing during aging and diabetes.

Topics: Aging; Cytokines; Diabetes Mellitus, Type 2; Glycation End Products, Advanced; Glycosylation; Humans; Inflammation; Interleukin-10; Interleukin-1beta; Interleukin-8; Macrophage Activation; Macrophages; Phagocytes; Pyruvaldehyde; Reactive Oxygen Species; THP-1 Cells; Tumor Necrosis Factor-alpha; Wound Healing

Fas/Fas ligand system was shown to be related to insulin resistance and type 2 diabetes mellitus (T2DM). However, the role of soluble Fas ligand (sFasL) in functioning of immune cells in type 2 diabetes mellitus (T2DM) has not been studied yet. The aim of the present study was to determine in vitro effects of sFasL on neutrophil activation and apoptosis. We demonstrate here that sFasL exhibited proinflammatory effect and induced mRNA levels of caspase-1, NF-κB, IL-1β and CD18 expression. At the same time, sFasL induced reactive oxygen species (ROS) production. Activation of caspase-1 activity abolished sFasL-dependent apoptosis, and suppressed Fas expression and mRNA levels of caspase-3 in neutrophils from T2DM patients. Collectively, our findings identify a novel proinflammatory role of sFasL in T2DM neutrophils that is dependent of caspase activity. Thus, sFasL enhances inflammatory response of neutrophils from T2DM patients without increasing apoptosis suggesting its triggering role in T2DM inflammation.

Topics: Adult; Apoptosis; Cells, Cultured; Diabetes Mellitus, Type 2; Fas Ligand Protein; Female; Humans; Interleukin-1beta; Interleukin-8; Male; Middle Aged; Neutrophil Activation; Neutrophils; RNA, Messenger

Inflammation has long been identified as an essential component of both Type-2 diabetes and tuberculosis. Chemokines are low molecular weight proteins which play an important role in both inflammation (diabetes) and immunity (tuberculosis).. In this study, we measured the serum levels of IP-10, IL-8 and SDF-1 in subjects with Normal Glucose Tolerance (NGT-TB. While IP-10 levels were significantly reduced in TB. Altered serum chemokine levels can alter anti-TB immunity in diabetes patients and can fuel DM-TB nexus.

Topics: Adult; Biomarkers; Case-Control Studies; Chemokine CXCL10; Chemokine CXCL12; Diabetes Mellitus, Type 2; Female; Humans; Inflammation; Interleukin-8; Male; Middle Aged; Signal Transduction; Tuberculosis, Pulmonary; Young Adult

To compare aqueous angiogenic and inflammatory cytokine concentrations in different patterns of diabetic macular edema (DME) based on optical coherence tomography (OCT).. This prospective study was conducted between July 1, 2015, and March 31, 2016, for 9 months. Aqueous samples were obtained from 52 consecutive DME patients and 16 controls. DME patients were divided according to OCT patterns into diffuse retinal thickening (DRT; n = 17), cystoid macular edema (CME; n = 20) and serous retinal detachment (SRD; n = 15) groups. Interleukin (IL)-6, IL-8, vascular endothelial growth factor (VEGF) and tumor necrosis factor alpha (TNF-α) levels were measured by RayBio. IL-6, IL-8 and VEGF levels differed significantly between three DME groups (p < 0.001 in all cases), but the differences in TNF-α levels were not significant (p = 0.226). VEGF and IL-6 levels correlated with central foveal thickness in DRT and SRD groups, respectively.. Aqueous cytokine levels vary with different morphological patterns of DME though the role of TNF-α needs to be studied further, and both anti-angiogenic and anti-inflammatory agents are required simultaneously for treatment of DME.

Topics: Aqueous Humor; Biomarkers; Cytokines; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Enzyme-Linked Immunosorbent Assay; Female; Follow-Up Studies; Fovea Centralis; Humans; Interleukin-6; Interleukin-8; Macular Edema; Male; Middle Aged; Prospective Studies; Severity of Illness Index; Tomography, Optical Coherence; Tumor Necrosis Factor-alpha; Vascular Endothelial Growth Factor A; Visual Acuity

Background We evaluated the association of cardiac adipose tissue including epicardial adipose tissue and pericardial adipose tissue with incident cardiovascular disease and mortality, coronary artery calcium, carotid intima media thickness and inflammatory markers. Design A prospective study of 200 patients with type 2 diabetes and elevated urinary albumin excretion rate (UAER). Methods Cardiac adipose tissue was measured from baseline echocardiography. The composite endpoint comprised incident cardiovascular disease and all-cause mortality. Coronary artery calcium, carotid intima media thickness and inflammatory markers were measured at baseline. Cardiac adipose tissue was investigated as continuous and binary variable. Analyses were performed unadjusted (model 1), and adjusted for age, sex (model 2), body mass index, low-density lipoprotein cholesterol, smoking, glycated haemoglobin, and systolic blood pressure (model 3). Results Patients were followed-up after 6.1 years for non-fatal cardiovascular disease ( n = 29) or mortality ( n = 23). Cardiac adipose tissue ( p = 0.049) and epicardial adipose tissue ( p = 0.029) were associated with cardiovascular disease and mortality in model 1. When split by the median, patients with high cardiac adipose tissue had a higher risk of cardiovascular disease and mortality than patients with low cardiac adipose tissue in unadjusted (hazard ratio 1.9, confidence interval: 1.1; 3.4, p = 0.027) and adjusted (hazard ratio 2.0, confidence interval: 1.1; 3.7, p = 0.017) models. Cardiac adipose tissue ( p =  0.033) was associated with baseline coronary artery calcium (model 1) and interleukin-8 (models 1-3, all p < 0.039). Conclusions In type 2 diabetes patients without coronary artery disease, high cardiac adipose tissue levels were associated with increased risk of incident cardiovascular disease or all-cause mortality even after accounting for traditional cardiovascular disease risk factors. High cardiac adipose tissue amounts were associated with subclinical atherosclerosis (coronary artery calcium) and with the pro-atherogenic inflammatory marker interleukin-8.

Topics: Adipose Tissue; Adiposity; Aged; Albuminuria; Biomarkers; Cardiovascular Diseases; Carotid Intima-Media Thickness; Coronary Angiography; Denmark; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Echocardiography; Female; Humans; Incidence; Inflammation Mediators; Interleukin-8; Kaplan-Meier Estimate; Linear Models; Male; Middle Aged; Nonlinear Dynamics; Pericardium; Prognosis; Proportional Hazards Models; Prospective Studies; Risk Assessment; Risk Factors; Time Factors

Obesity-linked ectopic fat accumulation is associated with the development of type 2 diabetes. Whether pancreatic and liver steatosis impairs insulin secretion is controversial. We examined the crosstalk of human pancreatic fat cells with islets and the role of diabetogenic factors, i.e. palmitate and fetuin-A, a hepatokine released from fatty liver.. Human pancreatic resections were immunohistochemically stained for insulin, glucagon, somatostatin and the macrophage/monocyte marker CD68. Pancreatic adipocytes were identified by Oil Red O and adiponectin staining. Primary pancreatic pre-adipocytes and differentiated adipocytes were co-cultured with human islets isolated from organ donors and the metabolic crosstalk between fatty liver and fatty pancreas was mimicked by the addition of palmitate and fetuin-A. Insulin secretion was evaluated by ELISA and RIA. Cytokine expression and secretion were assessed by RT-PCR and multiplex assay, respectively. Subcellular distribution of proteins was examined by confocal microscopy and protein phosphorylation by western blotting.. In human pancreatic parenchyma, highly differentiated adipocytes were detected in the proximity of islets with normal architecture and hormone distribution. Infiltration of adipocytes was associated with an increased number of CD68-positive cells within islets. In isolated primary pancreatic pre-adipocytes and differentiated adipocytes, palmitate and fetuin-A induced IL6, CXCL8 and CCL2 mRNA expression. Cytokine production was toll-like receptor 4 (TLR4)-dependent and further accentuated in pre-adipocytes when co-cultured with islets. In islets, IL6 and CXCL8 mRNA levels were also increased by fetuin-A and palmitate. Only in macrophages within the isolated islets, palmitate and fetuin-A stimulated the production of the cytotoxic cytokine IL-1β. Palmitate, but not fetuin-A, exerted pro-apoptotic effects in islet cells. Instead, fetuin-A impaired glucose-induced insulin secretion in a TLR4-independent, but c-Jun N-terminal kinase- and Ca. These results provide the first evidence that fetuin-A-mediated metabolic crosstalk of fatty liver with islets may contribute to obesity-linked glucose blindness of beta cells, while fatty pancreas may exacerbate local inflammation.

Topics: alpha-2-HS-Glycoprotein; Animals; Blotting, Western; Cells, Cultured; Chemokine CCL2; Diabetes Mellitus, Type 2; Fatty Liver; Humans; Immunohistochemistry; Inflammation; Insulin; Insulin Secretion; Insulin-Secreting Cells; Interleukin-6; Interleukin-8; Mice; Palmitates; Pancreas; Toll-Like Receptor 4

Interleukin-8 (IL-8) is a chemokine involved in systemic immunity, macrophages infiltration and activation in adipose tissue and may play a significant role in the pathogenesis of type 2 diabetes (T2D) and atherosclerosis. Aims of this study were to evaluate circulating IL-8 levels in adult patients with T2D in comparison with non-diabetic subjects and to describe clinical and biochemical correlates of IL-8 concentration.. For this cross-sectional study, we enrolled 79 consecutive T2D individuals referring to our diabetes outpatient clinics at Sapienza University of Rome, and 37 sex, age and BMI comparable non-diabetic subjects as a control group. Clinical parameters and medical history were recorded; fasting blood sampling was performed for biochemistry and for measuring serum IL-8, IL-6, TNF-α, CRP, adiponectin and 25(OH)vitamin D [25(OH)D] levels.. Patients with T2D exhibited significantly higher serum IL-8 levels than non-diabetic subjects (69.27 ± 112.83 vs. 16.03 ± 24.27 pg/mL, p < 0.001). In diabetic patients, increased IL-8 concentration correlated with higher IL-6 (p < 0.001), TNF-α (p = 0.02), FBG (p = 0.035), HbA1c (p = 0.04) and LDL-C (p = 0.04) and with lower adiponectin (p = 0.02) and 25(OH)D (p = 0.003) concentrations.. Patients with T2D display a marked elevation of circulating IL-8 levels which identify subjects with worse inflammatory, glycometabolic and lipid profile and lower vitamin D levels. Further studies are warranted for evaluating a possible role of IL-8 as a novel marker for risk stratification in T2D patients.

Topics: Adiponectin; Adult; Biomarkers; Calcifediol; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Female; Humans; Interleukin-6; Interleukin-8; Male; Middle Aged; Tumor Necrosis Factor-alpha

Periodontitis is closely linked with type 2 diabetes mellitus (T2DM) and endothelial dysfunction. This study investigated the effects of periodontal treatment on immuno-inflammatory gene expression of endothelial progenitor cells (EPCs) in diabetic patients.. Eighteen T2DM patients with moderate to severe chronic periodontitis were randomly assigned to the Treatment group with oral hygiene instruction (OHI), scaling and root debridement (n = 11), and Control group (n = 7) with OHI alone. Peripheral blood samples were taken for biochemical analysis and culture of EPCs at baseline and 6 months after the treatment. PCR array-based profiling of 84 Toll-like receptor signalling-related genes in EPCs was firstly assessed for four randomly selected patients from the Treatment group. The differentially expressed genes were then further validated by qPCR in both groups.. All subjects in the Treatment group significantly improved their periodontal conditions. Among the 84 genes tested, IL-6 and IL-8 transcripts were significantly downregulated with over twofold change after the treatment, and this observation was further validated by qPCR in all subjects from both groups (p < .05).. This preliminary study suggests that periodontal treatment may contribute to a notable reduction in immuno-inflammatory gene expression measured by IL-6 and IL-8 transcripts in EPCs.

Topics: Adolescent; Adult; Aged; Cell Culture Techniques; Child; Chronic Periodontitis; Dental Plaque Index; Dental Scaling; Diabetes Mellitus, Type 2; Endothelial Progenitor Cells; Female; Gene Expression; Hong Kong; Humans; Inflammation; Interleukin-6; Interleukin-8; Male; Middle Aged; Oral Hygiene; Periodontal Index; Periodontal Pocket; Treatment Outcome; Young Adult

Clinical trials suggest that fenofibrate reduces the progression of retinopathies in patients with type 2 diabetes. Furthermore, patients with retinopathies have elevated levels of inflammatory chemokines and dysfunctional retinal angiogenesis. Therefore, we investigated the effects of fenofibrate on the production of inflammatory chemokines and genes associated with angiogenesis. Retinal pigment epithelial cells (RPECs) were cultured with IL-1β and fenofibrate ranging from 1-50 μM. ENA-78, IL-8, and RANTES were measured in cell culture by ELISA. ENA-78, ABCA1, and ABCG1 gene expression were tested by RT-PCR. IL-1β significantly induced the production of ENA-78, IL-8, and RANTES. Fenofibrate at concentrations of 25-50 uM blunted the IL-1β induced production of ENA-78 (p < 0.05) with no significant effects on RANTES and IL-8. Fenofibrate also reduced the expression of the ENA-78 gene as well as ABCA1 and ABCG1, which are genes involved in angiogenesis. Fenofibrate decreases ENA-78 production and ABCA1/ABCG1 gene expression in RPECs.

Topics: ATP Binding Cassette Transporter 1; ATP Binding Cassette Transporter, Subfamily G, Member 1; Biomarkers; Cells, Cultured; Chemokine CCL5; Chemokine CXCL5; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Enzyme-Linked Immunosorbent Assay; Epithelial Cells; Fenofibrate; Humans; Hypolipidemic Agents; Interleukin-1beta; Interleukin-8; Neovascularization, Pathologic; Real-Time Polymerase Chain Reaction; Retinal Pigment Epithelium

Topics: Adiponectin; Adult; Biomarkers; C-Reactive Protein; Depression; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Humans; Inflammation; Intercellular Adhesion Molecule-1; Interleukin-6; Interleukin-8; Male; Middle Aged; Young Adult

Accumulation of advanced glycation end products (AGEs) is a major cause of diabetes mellitus (DM) skin complications. Methylglyoxal (MGO), a reactive dicarbonyl compound, is a crucial intermediate of AGEs generation. N-acetyl-L-cysteine (NAC), an active ingredient of some medicines, can induce endogenous GSH and hydrogen sulfide generation, and set off a condensation reaction with MGO. However, there is rare evidence to show NAC can alleviate DM-induced skin injury through inhibition of AGEs generation or toxicity. The present study aimed to observe the effects of NAC on MGO-induced inflammatory injury and investigate the roles of AGEs and its receptor (RAGE) in NAC's dermal protection in human HaCaT keratinocytes.. The cells were exposed to MGO to simulate a high MGO status in diabetic blood or tissues. The content of AGEs in serum or cell medium was measured with ELISA. The protective effects of NAC against MGO-induce injury were evaluated by administration before MGO one hour, in virtue of cell viability, mitochondrial membrane potential, inflammation reaction, nuclear factor (NF)-κB activation, matrix metalloproteinase (MMP)-9 expression, as well as cellular behavioral function.. We found the AGEs levels of patients with DM were elevated comparing with healthy volunteers. The in vitro AGEs generation was also able to be enhanced by the exposure of HaCaT cells to MGO, which reduced dose-dependently cellular viability, damaged mitochondrial function, triggered secretion of interleukin (IL)-6 and IL-8, activated NF-κB and upregulated MMP-9 expression. Furthermore, the exposure caused cellular adhesion and migration dysfunction, as well as collagen type I inhibition. Importantly, before the exposure to MGO, the preconditioning with NAC significantly attenuated MGO-induced AGEs generation, improved cellular viability and mitochondrial function, partially reversed the overexpression of proinflammatory factors and MMP-9, as well as the activation of NF-κB. Lastly, NAC blocked MGO-induced RAGE upregulation, and inhibition of RAGE with its neutralizing antibody significantly alleviated MGO-induced NF-κB activation, MMP-9 upregulation and inflammatory injury in HaCaT cells.. The present work indicates the administration of NAC can prevent MGO-induced dermal inflammatory injury through inhibition of AGEs/RAGE signal, which may provide a basal support for the treatment of diabetic skin complications with NAC-containing medicines in the future.

Topics: Acetylcysteine; Aged; Case-Control Studies; Cell Adhesion; Cell Line; Cell Movement; Cell Survival; Diabetes Mellitus, Type 2; Female; Glycation End Products, Advanced; Humans; Interleukin-6; Interleukin-8; Male; Matrix Metalloproteinase 9; Membrane Potential, Mitochondrial; Middle Aged; Mitochondria; Protective Agents; Pyruvaldehyde; Receptor for Advanced Glycation End Products; Up-Regulation

In cells and tissues resistin affects IL-1β, IL-6, IL-8, IL-12 and TNF-α expression, thus suggesting the existence of a multi-cytokine "resistin pathway". We investigated whether such pathway does exist in humans and, if so, if it is associated with cardiovascular risk factors and with major adverse cardiovascular events (MACE). Serum cytokines were measured in 280 healthy subjects from the Gargano Study 2 (GS2) whose BMI, waist circumference, HOMA

Topics: Adult; Aged; Blood Pressure; Body Mass Index; Case-Control Studies; Cholesterol, HDL; Cholesterol, LDL; Coronary Artery Disease; Diabetes Mellitus, Type 2; Female; Gene Expression Regulation; Humans; Insulin Resistance; Interleukin-12; Interleukin-1beta; Interleukin-6; Interleukin-8; Male; Middle Aged; Prospective Studies; Resistin; Risk Factors; Signal Transduction; Triglycerides; Tumor Necrosis Factor-alpha; Waist Circumference

The antidiabetic effects of Lactobacillus. paracasei subsp. paracasei G15 and Lactobacillus. casei Q14 in high fat diet and streptozotocin-induced type 2 diabetic (T2D) rats were evaluated in this study. The strains were separated from Chinese traditional fermented dairy food. Administration of G15 and Q14 for 6 weeks significantly improved the glucose tolerance and reduced the HbA1c levels in T2D rats. The probiotic treatment reduced the intestinal mucosal permeability and improved the epithelial barrier function through modification of the gut microbiota, which in turn lowered circulating LPS and inflammation cytokines, including IL-1β and IL-8, and eventually alleviated the inflammatory status and islet β-cell dysfunction. Combination of Q14 and metformin reversed the thymic atrophy and both G15 and Q14 lowered the circulating IL-6 level, indicating the immune-modulating potential of the strains. Lactobacillus. paracasei subsp. paracasei G15 and Lactobacillus. casei Q14 provide an insight into the biotherapy application of traditional fermented foods and their functional ingredients in the treatment of diabetes.

Topics: Animals; Cultured Milk Products; Diabetes Mellitus, Type 2; Gastrointestinal Microbiome; Glucose Intolerance; Glucose Tolerance Test; Glycated Hemoglobin; Inflammation; Interleukin-1beta; Interleukin-8; Intestinal Mucosa; Lacticaseibacillus casei; Lacticaseibacillus paracasei; Lipopolysaccharides; Male; Permeability; Rats; Rats, Wistar

Reduced capillary density is a feature of skeletal muscle (SkM) in type 2 diabetes (T2D), which is associated with multiple metabolic and functional abnormalities. SkM has been identified as a secretory tissue, releasing myokines that regulate multiple processes, including vascularization. We sought to determine how myokines secreted from T2D myotubes might influence SkM angiogenesis. Conditioned media (CM) were generated by myotubes from T2D and nondiabetic (ND) subjects. Primary human endothelial cells (HUVEC) and SkM explants were exposed to CM or recombinant myokines, and tube number or capillary outgrowth was determined as well as measurement of protein expression and phosphorylation. CM from ND myotubes stimulated tube formation of HUVEC to a greater extent than T2D myotubes (T2D-CM = 100%, ND-CM = 288 ± 90% after 48 h, P < 0.05). The effects of T2D myotube CM were mediated by IL-8, not IL-15 or GROα, and were due not to cell damage but rather through regulating tube production and maintenance (response to T2D-IL-8 = 100%, response to ND-IL-8 = 263 ± 46% after 48 h, P < 0.05). A similar effect was seen in SkM explants with exposure to IL-8. The dose-dependent effect of IL-8 on tube formation was also observable in the PI3K and FAK signaling pathways and mediated at least in part by PI3K, leading to regulation of Tie2 expression. These results suggest that elevated levels of IL-8 secreted from T2D myotubes create a muscle microenvironment that supports reduced capillarization in T2D. Impaired vascularization of SkM limits the availability of substrates, including glucose and contributes to the T2D phenotype.

Topics: Case-Control Studies; Cell Proliferation; Cells, Cultured; Diabetes Mellitus, Type 2; Female; Human Umbilical Vein Endothelial Cells; Humans; Interleukin-8; Male; Middle Aged; Muscle Fibers, Skeletal; Muscle, Skeletal; Phosphatidylinositol 3-Kinases; Receptor, TIE-2; Signal Transduction

Pathological changes in periodontal tissues are mediated by the interaction between microorganisms and the host immune-inflammatory response. Hyperglycemia may interfere with this process. The aim of this study was to compare the levels of 27 inflammatory molecules in the gingival crevicular fluid (GCF) of patients with type 2 diabetes, with and without chronic periodontitis, and of chronic periodontitis subjects without diabetes. A putative correlation between glycated haemoglobin (HbA1c) and levels of the inflammatory molecules was also investigated.. The study population comprised a total of 108 individuals, stratified into: 54 with type 2 diabetes and chronic periodontitis (DM + CP), 30 with chronic periodontitis (CP) and 24 with type 2 diabetes (DM). Participants were interviewed with the aid of structured questionnaire. Periodontal parameters (dental plaque, bleeding on probing and periodontal pocket depth) were recorded. The GCF levels of the 27 inflammatory molecules were measured using multiplex micro-bead immunoassay. A glycated haemoglobin (HbA1c) test was performed for patients with diabetes by boronate affinity chromatography.. After adjustment for potential confounders, the DM + CP group had higher levels of IL-8 and MIP-1β, and lower levels of TNF-α, IL-4, INF-γ, RANTES and IL-7 compared to the CP group. Moreover, the DM + CP group had lower levels of IL-6, IL-7 and G-CSF compared to the DM group. The DM group had higher levels of IL-10, VEGF, and G-CSF compared to the CP group. The levels of MIP-1α and FGF were lower in diabetes patients (regardless of their periodontal status) than in chronic periodontitis subjects without diabetes. Diabetes patients (DM + CP and DM) had higher Th-2/Th-1 ratio compared to the CP group. HbA1c correlated positively with the pro-inflammatory cytokines (Pearson correlation coefficient = 0.27, P value: 0.02).. Type 2 diabetes and chronic periodontitis may influence the GCF levels of inflammatory molecules synergistically as well as independently. Type 2 diabetes was associated with high Th-2/Th-1 ratio, and modulated the local expression of molecules involved in the anti-inflammatory and healing processes.

Topics: Adult; Aged; Chemokine CCL3; Chemokine CCL4; Chemokine CCL5; Chronic Periodontitis; Cross-Sectional Studies; Dental Plaque Index; Diabetes Mellitus, Type 2; Female; Fibroblast Growth Factors; Gingival Crevicular Fluid; Glycated Hemoglobin; Granulocyte Colony-Stimulating Factor; Humans; Inflammation Mediators; Interferon-gamma; Interleukin-10; Interleukin-4; Interleukin-6; Interleukin-7; Interleukin-8; Male; Middle Aged; Periodontal Index; Th1 Cells; Th2 Cells; Tumor Necrosis Factor-alpha; Vascular Endothelial Growth Factor A; Young Adult

The aim of this conventional case-control study was to investigate the prevalence and relationship between Helicobacter pylori infection in type 2 diabetes mellitus (DM) and diabetic nephropathy (DN).. A total of 241 type 2 DM patients and 69 non-diabetic subjects with dyspeptic symptoms were enrolled in the study. Gastroduodenal lesions were observed by gastrointestinal endoscopy and the presence of H. pylori was identified by rapid urease test and serum IgG antibodies to H. pylori. According to the urinary albumin excretion rate (UAE), patients were classified into diabetes mellitus group (DM group, with UAE <30 mg/24h); diabetic nephropathy group 1 (DN group 1, with UAE 30 mg/24 h to <300 mg/24 h); and diabetic nephropathy group 2 (DN group 2 ≥ 300 mg/24 h). The 69 non-diabetic subjects were used as control group. The serum levels of inflammatory factors such as tumor necrosis factor-α (TNF-α) and interleukin (IL)-8 were determined using ELISA.. The prevalence of H. pylori infection in DN group 1 and DN group 2 was 45/72 (62.5%) and 34/53 (64.15%), respectively, which was significantly higher than in control [28/65 (43.1%)] and DM groups [42.9% (27/63)]. No significant differences of H. pylori prevalence were detected between DN groups as well as DM and control groups. Interestingly, in both DN groups, higher levels of IL-8, TNF-α and urinary albumin excretion rate were found in H. pylori positive subjects.. Diabetic nephropathy patients are more susceptible to H. pylori infection. Our data support an association between H. pylori infection and diabetic nephropathy.

Topics: Adult; Albuminuria; Case-Control Studies; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Female; Helicobacter Infections; Helicobacter pylori; Humans; Interleukin-8; Male; Middle Aged; Prevalence; Tumor Necrosis Factor-alpha

To examine for the first time the associations between pro-inflammatory cytokines and obesity-related metabolic biomarkers in, exclusively prepubertal, otherwise healthy obese and non-obese Black and White children, 7-9 years of age.. Body mass index (BMI), homeostasis model assessment-estimated insulin resistance, visceral adipose tissue and subcutaneous adipose tissue (SAT (magnetic resonance imaging)); total body fat (dual-energy X-ray absorptiometry), ectopic, intrahepatic lipid (IHL) and intramyocellular lipid (IMCL) fat (proton magnetic resonance spectroscopy) and serum levels of interleukin (IL)-1, IL-6, IL-8, tumor necrosis factor alpha (TNF-α) and monocyte chemoattractant protein-1 were measured in 40 obese and non-obese children. Relationships between inflammatory cytokines and obesity were assessed by analysis of variance and Spearman's rank correlation.. Significant inverse correlations were found between BMI z-score, SAT, total BF, and IHL and levels of TNF-α (Spearman's ρ=-0.36, -0.39, -0.43 and -0.39, respectively; P<0.05). Levels of IL-8 were significantly and inversely correlated with IMCL (-0.39; P=0.03) and remained significant after adjusting for race. IMCL was inversely associated with TNF-α only after adjusting for race (-0.37; P=0.04).. Relationships between pro-inflammatory and metabolic markers commonly observed in adults are reversed in healthy, Black and White children before puberty. Prospective studies are warranted to determine how these inverse relationships modify chronic disease risk later in life.

Topics: Absorptiometry, Photon; Biomarkers; Black or African American; Blood Glucose; Body Composition; Cardiovascular Diseases; Child; Diabetes Mellitus, Type 2; Female; Humans; Inflammation; Insulin Resistance; Interleukin-1; Interleukin-6; Interleukin-8; Intra-Abdominal Fat; Lipid Metabolism; Lipids; Male; Pediatric Obesity; Puberty; Subcutaneous Fat; Tumor Necrosis Factor-alpha; White People

Diabetes has been associated with periodontitis, but the mechanisms through which periodontal diseases affect the metabolic control remain unclear.. This study aimed to evaluate serum leveis of inflammatory markers, IL-8, IL-6 and monocyte chemoattractant protein 1 (MCP-1), in type 2 diabetic patients in the presence of chronic periodontitis.. Forty two individuals were enrolled in this study and assigned to one of five groups: diabetes mellitus with inadequate glycemic control and periodontitis (DMI+P, n = 10), diabetes mellitus with adequate glycemic control and periodontitis (DMA+P, n = 10), diabetes mellitus without periodontitis (DM, n = 10), periodontitis without diabetes (P, n=6), and neither diabetes nor periodontitis (H, n = 6). Periodontal clinical examination included visible plaque index (PL), gingival bleeding index (GB), probing depth (PD), attachment level (AL) and bleeding on probing (BP). Glycemic control was evaluated by serum concentration of glycated hemoglobin (HbAlc). Inflammatory serum markers IL-8, IL-6 and (MCP-1) were measured by ELISA.. DMI+P and DMA+P groups presented higher PD (p=0.025) and AL (p=0.003) values when compared to the P group. There were no significant differences among groups for IL-6, IL-8 and MCP-1 serum levels.. Although periodontitis was more severe in diabetic patients, the serum levels of the investigated inflammatory markers did not differ among the groups.

Topics: Adult; Aged; Biomarkers; Chemokine CCL2; Chronic Periodontitis; Dental Plaque Index; Diabetes Complications; Diabetes Mellitus, Type 2; Enzyme-Linked Immunosorbent Assay; Female; Glycated Hemoglobin; Humans; Interleukin-6; Interleukin-8; Male; Middle Aged; Periodontal Index; Statistics, Nonparametric

Increasing evidence indicates that diabetes mellitus increases the incidence and severity of periodontitis. Toll-like receptors (TLRs) play a role in the pathogenic processes of diabetes and its complications, but the effect of high glucose on TLRs in patients with diabetes and periodontitis is still unclear.. Two kinds of diabetes rat models were established. Human gingival epithelial cells (HGECs) were established and challenged with Porphyromonas gingivalis lipopolysaccharide (LPS) in the context of high glucose in vitro. The expressions of TLR2 and TLR4 were detected using immunohistochemistry, quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and flow cytometry. The TLR4 inhibitor ethyl (6R)-6-[(2-chloro-4-fluorophenyl)sulfamoyl]cyclohexene-1-carboxylate (TAK-242) was applied to block the TLR4 in HGECs, and the inflammatory factors were detected by qRT-PCR.. The expression of TLR2 and TLR4 in gingival tissue from both rat diabetes models was significantly increased compared with that of healthy controls. Moreover, TLR4 expression was also markedly increased in HGECs incubated with high glucose. The expression of interleukin (IL)-6, IL-8, and monocyte chemoattractant protein-1 were significantly increased in HGECs while challenged with LPS in the context of high glucose; however, the expression inflammatory cytokines were decreased significantly, whereas TLR4 was blocked by TAK-242.. High glucose contributes to an upregulated expression of TLR4 in gingival epithelium, and TLR4-dependent inflammatory response may promote the susceptibility to periodontitis in patients with diabetes.

Topics: Adult; Animals; Cells, Cultured; Chemokine CCL2; Diabetes Mellitus, Type 2; Epithelial Cells; Female; Gingiva; Glucose; Humans; Inflammation Mediators; Interleukin-6; Interleukin-8; Lipopolysaccharides; Male; Porphyromonas gingivalis; Rats; Rats, Inbred OLETF; Rats, Long-Evans; Rats, Sprague-Dawley; Sulfonamides; Toll-Like Receptor 2; Toll-Like Receptor 4; Young Adult

Like most natural product libraries animal venoms have long been recognized as potentially rich source of biologically active molecules with the potential to be mined for the discovery of drugs, drug leads and/or biosimilars. In this work we demonstrate as a proof of concept a novel approach to explore venoms for potential biosimilarity to other drugs based on their ability to alter the transcriptomes of test cell lines followed by informatic searches and Connectivity Mapping to match the action of the venom on the cell gene expression to that of other drugs in the Connectivity Map (C-Map) database. As our test animal venom we chose Heloderma suspectum venom (Gila monster) since exendin-4, a glucagon-like peptide 1 receptor agonist, isolated from the venom is currently on the market to treat type 2 diabetes. The action of Byetta(®) (exentide, synthetic exendin-4), was also used in transcriptome studies. Analysis of transcriptomes from cells treated with the venom or the drug showed similarities as well as differences. The former case was primarily attributed to the fact that Gila monster venom likely contains a variety of biologically active molecules that could alter the MCF7 cell transcriptome compared to that of the single perturbant Byetta(®). Using Ingenuity Pathway Analysis software, insulin-like growth factor 1 signaling was identified in the category of "Top Canonical Pathways" for both the venom and Byetta(®). In the category of "Top Molecules" up-regulated, both venom and Byetta(®) shared IL-8, cyclic AMP-dependent transcription factor 3 (ATF-3), neuron-derived orphan receptor 1 (NR4A3), dexamethasone-induced Ras-related protein 1 (RASD1) and early growth response protein 1, (EGR-1) all with potential relevance in diabetes. Using Connectivity Mapping, Gila monster venom showed positive correlation with 1732 instances and negative correlation with 793 instances in the Connectivity database whereas Byetta(®) showed positive correlation with 1692 instances and negative correlation with 868 instances. Interestingly, the Gila monster venom and Byetta(®) both showed positive correlation with the anti-diabetic drugs troglitazone, of the thiazolidinedione class, and metformin, of the biguanide class, although Byetta(®) as a glucagon-like peptide-1 (GLP-1) agonist functions in a different manner than either of these two classes of anti-diabetic drugs. In summary, despite the fact that Gila monster venom contains a mixture of biologically active molecules

Topics: Activating Transcription Factor 3; Animals; Biosimilar Pharmaceuticals; Computational Biology; Diabetes Mellitus, Type 2; DNA-Binding Proteins; Drug Discovery; Early Growth Response Protein 1; Exenatide; Glucagon-Like Peptide-1 Receptor; Humans; Hypoglycemic Agents; Interleukin-8; Lizards; MCF-7 Cells; Peptides; ras Proteins; Receptors, Glucagon; Receptors, Steroid; Receptors, Thyroid Hormone; Thiazolidinediones; Venoms

In this present study, we aimed: (i) To clarify if prediabetes is associated with subclinical inflammation independent of underlying obesity, and (ii) to evaluate the effect of postload glucose concentration on subclinical inflammation markers in a group of patients with elevated fasting glucose.. In a cohort of 165 patients with newly detected fasting hyperglycemia, according to 75 g oral glucose tolerance test (OGTT), subjects were classified either as newly diagnosed type 2 diabetes (diabetes group, n = 40), impaired fasting glucose (IFG) plus impaired glucose tolerance (IGT) (IFG/IGT group, n = 42) or IFG only (IFG group, n = 83). A control group (n = 47) consisted of age- and body mass index (BMI)-matched healthy subjects with a normal OGTT. Circulating concentrations of lipids, insulin, interleukin-6 (IL-6), interleukin-8 (IL-8) and high sensitive C-reactive protein (hsCRP) were measured. HOMA index was calculated.. Subclinical inflammation markers were elevated in patients with diabetes and IFG/IGT compared to healthy controls and also IFG patients (diabetes vs. control: p < 0.05 for hsCRP, IL-8, and IL-6; IFG/IGT vs. control: p < 0.05 for hsCRP, and IL-6; diabetes vs. IFG: p < 0.05 for hsCRP, and IL-6; IFG/IGT vs. IFG: p < 0.05 for hsCRP, and IL-6). In multiple regression analysis, postload glucose concentration was independently associated with circulating hsCRP and IL-6 concentrations when the data was controlled for age, gender, BMI and lipid concentrations (p < 0.05 for hsCRP, and IL-6).. Our results suggest that patients with prediabetes, independent of underlying obesity, have increased concentrations of subclinical inflammation which is mostly driven by postload glucose concentrations.

Topics: Adult; Asymptomatic Diseases; Blood Glucose; C-Reactive Protein; Case-Control Studies; Diabetes Mellitus, Type 2; Female; Glucose Intolerance; Glucose Tolerance Test; Humans; Inflammation; Inflammation Mediators; Interleukin-6; Interleukin-8; Male; Middle Aged; Obesity; Prediabetic State

Type 2 diabetes mellitus is a major risk factor for melioidosis, which is caused by Burkholderia pseudomallei. Our previous study has shown that polymorphonuclear neutrophils (PMNs) from diabetic subjects exhibited decreased functions in response to B. pseudomallei. Here we investigated the mechanisms regulating cytokine secretion of PMNs from diabetic patients which might contribute to patient susceptibility to bacterial infections. Purified PMNs from diabetic patients who had been treated with glibenclamide (an ATP-sensitive potassium channel blocker for anti-diabetes therapy), showed reduction of interleukin (IL)-1β and IL-8 secretion when exposed to B. pseudomallei. Additionally, reduction of these pro-inflammatory cytokines occurred when PMNs from diabetic patients were treated in vitro with glibenclamide. These findings suggest that glibenclamide might be responsible for the increased susceptibility of diabetic patients, with poor glycemic control, to bacterial infections as a result of its effect on reducing IL-1β production by PMNs.

Topics: Burkholderia pseudomallei; Diabetes Mellitus, Type 2; Disease Susceptibility; Glyburide; Humans; Hypoglycemic Agents; Interleukin-1beta; Interleukin-8; Melioidosis; Metformin; Neutrophils; Thailand

The present study evaluates a hypothesis that sour cherry (Prunus cerasus) seed extracts (SCE) modulate CD3+ T lymphocyte activity in ways predictive of potential for uses of SCE in management of inflammatory diseases. Peripheral blood mononuclear cells (PBMC) from 12 type 2 diabetes (T2DM) patients and eight healthy control subjects were cultured 24 h with 100 ng/ml lipopolysaccharide (LPS) to increase inflammatory signaling and co-incubated with 0.5-100 µg/ml SCE. Cultures were evaluated by two-color flow cytometry for percent representation of CD3+ IL8+ and CD3+TNF-α cells which express interleukin-8 (IL-8), and tumor necrosis factor-α, (TNF-α+) respectively, and by enzyme-linked immunoassay for lymphocyte-associated heme oxygenase-1 (HO-1, known to be induced by SCE). SCE dosage ranges of 0.5-100 µg/ml in cell cultures significantly suppressed LPS-increased CD3+TNF-α+ and CD3+IL8+ representation from all participants (p < 0.05), with greater pharmacological effect noted in suppression of CD3+TNF-α+ noted in cells from T2DM patients versus healthy control subjects. These effects correlated with increased HO-1 expression in SCE-treated PBMC from all subjects (p < 0.05). Since TNF-α and IL-8 are diagnostic/prognostic biomarkers for many inflammatory syndromes, the capacity of SCE to down-regulate representation of cells that express them suggests potential for therapeutic use of SCE in T2DM and other diseases.

Topics: CD3 Complex; Cells, Cultured; Diabetes Mellitus, Type 2; Female; Heme Oxygenase-1; Humans; Interleukin-8; Leukocytes, Mononuclear; Lymphocyte Subsets; Male; Middle Aged; Plant Extracts; Prunus; Seeds; Tumor Necrosis Factor-alpha

Inflammatory markers have been observed in proliferative diabetic retinopathy (PDR). We assessed vitreous concentrations of adhesion molecules and cytokines in PDR and non-diabetic controls and plasma concentrations to differentiate local inflammation from the breakdown of the blood-retina barrier.. 38 patients with PDR and 16 controls with macular hole or epiretinal membrane underwent vitrectomy. Vitreous and plasma soluble adhesion molecules [sE-selectin, intercellular adhesion molecule (sICAM)-1 and -3, platelet-endothelial cell adhesion molecule (sPECAM)-1, sP-selectin, vascular cell adhesion molecule (sVCAM)-1] and cytokines [interleukin (IL)-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12 (p70), tumour necrosis factor-α and -β, γ-interferon] were detected by the multiplex assay.. Levels of IL-6 and IL-8 were 26-fold (p = 0.001) and 6-fold higher (p = 0.001) in vitreous than in plasma in PDR. Vitreous IL-10 (p = 0.004), sPECAM-1, sE-selectin, sICAM-1 and sVCAM-1 were higher in PDR than controls (p = 0.001 for all). Adhesion molecule concentrations in vitreous in PDR were less than 10% of those in plasma. IL-10 was lower in vitreous than plasma (3.0 vs. 12.8 pg/ml, p = 0.007), and the vitreous IL-10/IL-8 ratio was significantly lower in PDR than in controls (0.10 vs. 0.55 pg/ml, p = 0.003).. The elevated IL-6 and IL-8 levels in vitreous, but not in plasma, are evidence favouring local over systemic inflammation in PDR. Furthermore, there was imbalance between inflammatory and anti-inflammatory cytokines in the vitreous.

Topics: Aged; Cell Adhesion Molecules; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Female; Humans; Interleukin-6; Interleukin-8; Macular Edema; Male; Middle Aged; Retinal Perforations; Vitrectomy; Vitreous Body

Obesity, type 2 diabetes, and HIV-associated lipodystrophy are associated with abnormalities in adipocyte growth and differentiation. In persons with these conditions, adipose depots contain increased numbers of macrophages, but the origins of these cells and their specific effects are uncertain. Peripheral blood mononuclear cells (PBMC)-derived monocytes, but not T cells, cocultured via transwells with primary subcutaneous preadipocytes, increased proliferation (approximately twofold) and reduced differentiation (~50%) of preadipocytes. Gene expression analyses in proliferating preadipocytes (i.e., prior to hormonal induction of terminal differentiation) revealed that monocytes down-regulated mRNA levels of CCAAT/enhancer binding protein, alpha (C/EBPα) and up-regulated mRNA levels of G0/G1 switch 2 (G0S2) message, genes important for the regulation of adipogenesis and the cell cycle. These data indicate that circulating peripheral blood monocytes can disrupt adipogenesis by interfering with a critical step in C/EBPα and G0S2 transcription required for preadipocytes to make the transition from proliferation to differentiation. Interactions between preadipocytes and monocytes also increased the inflammatory cytokines IL-6 and IL-8, as well as a novel chemotactic cytokine, CXCL1. Additionally, the levels of both IL-6 and CXCL1 were highest when preadipocytes and monocytes were cultured together, compared to each cell in culture alone. Such cross-talk amplifies the production of mediators of tissue inflammation.

Topics: Adipocytes; Adipose Tissue; Blotting, Western; CCAAT-Enhancer-Binding Protein-alpha; Cell Differentiation; Cell Proliferation; Chemokine CXCL1; Cytokines; Diabetes Mellitus, Type 2; HIV-Associated Lipodystrophy Syndrome; Humans; Interleukin-6; Interleukin-8; Monocytes; Obesity; Real-Time Polymerase Chain Reaction; RNA, Messenger

Diabetic nephropathy (DN) is one of the major diabetic complications and the leading cause of end-stage renal disease. In early DN, renal injury and macrophage accumulation take place in the pathological environment of glomerular vessels adjacent to renal mesangial cells expressing proinflammatory mediators. Purple corn utilized as a daily food is rich in anthocyanins exerting disease-preventive activities as a functional food. This study elucidated whether anthocyanin-rich purple corn extract (PCA) could suppress monocyte activation and macrophage infiltration. In the in vitro study, human endothelial cells and THP-1 monocytes were cultured in conditioned media of human mesangial cells exposed to 33 mM glucose (HG-HRMC). PCA decreased the HG-HRMC-conditioned, media-induced expression of endothelial vascular cell adhesion molecule-1, E-selectin, and monocyte integrins-β1 and -β2 through blocking the mesangial Tyk2 pathway. In the in vivo animal study, db/db mice were treated with 10 mg/kg PCA daily for 8 wk. PCA attenuated CXCR2 induction and the activation of Tyk2 and STAT1/3 in db/db mice. Periodic acid-Schiff staining showed that PCA alleviated mesangial expansion-elicited renal injury in diabetic kidneys. In glomeruli, PCA attenuated the induction of intracellular cell adhesion molecule-1 and CD11b. PCA diminished monocyte chemoattractant protein-1 expression and macrophage inflammatory protein 2 transcription in the diabetic kidney, inhibiting the induction of the macrophage markers CD68 and F4/80. These results demonstrate that PCA antagonized the infiltration and accumulation of macrophages in diabetic kidneys through disturbing the mesangial IL-8-Tyk-STAT signaling pathway. Therefore, PCA may be a potential renoprotective agent treating diabetes-associated glomerulosclerosis.

Topics: Animals; Anthocyanins; Diabetes Mellitus, Type 2; Diabetic Nephropathies; E-Selectin; Human Umbilical Vein Endothelial Cells; Humans; Integrins; Intercellular Adhesion Molecule-1; Interleukin-8; Kidney; Macrophages; Mice; Monocytes; Plant Extracts; Signal Transduction; Vascular Cell Adhesion Molecule-1; Zea mays

Endothelial progenitor cells (EPCs) are decreased in number and function in type 2 diabetes. Mechanisms by which this dysfunction occurs are largely unknown. We tested the hypothesis that a chronic inflammatory environment leads to insulin signaling defects in EPCs and thereby reduces their survival. Modifying EPCs by a knockdown of nuclear factor-κB (NF-κB) can reverse the insulin signaling defects, improve EPC survival, and decrease neointimal hyperplasia in Zucker fatty rats postangioplasty.. EPCs from Zucker fatty insulin-resistant rats were cultured and exposed to tumor necrosis factor-α (TNF-α). Insulin signaling defects and apoptosis were measured in the presence and absence of an NF-κB inhibitor, BAY11. Then, EPCs were modified by a knockdown of NF-κB (RelA) and exposed to TNF-α. For in vivo experiments, Zucker fatty rats were given modified EPCs post-carotid angioplasty. Tracking of EPCs was done at various time points, and neointimal hyperplasia was measured 3 weeks later.. Insulin signaling as measured by the phosphorylated-to-total AKT ratio was reduced by 56% in EPCs exposed to TNF-α. Apoptosis was increased by 71%. These defects were reversed by pretreatment with an NF-κB inhibitor, BAY11. Modified EPCs exposed to TNF-α showed a lesser reduction (RelA 20%) in insulin-stimulated AKT phosphorylation versus a 55% reduction in unmodified EPCs. Apoptosis was 41% decreased for RelA knockdown EPCs. Noeintimal hyperplasia postangioplasty was significantly less in rats receiving modified EPCs than in controls (intima-to-media ratio 0.58 vs. 1.62).. In conclusion, we have shown that insulin signaling and EPC survival is impaired in Zucker fatty insulin resistant rats. For the first time, we have shown that this defect can be significantly ameliorated by a knockdown of NF-κB and that these EPCs given to Zucker fatty rats decrease neointimal hyperplasia post-carotid angioplasty.

Topics: Animals; Apoptosis; Cells, Cultured; Diabetes Mellitus, Type 2; Endothelial Cells; Enzyme-Linked Immunosorbent Assay; Inflammation; Insulin Resistance; Interleukin-8; NF-kappa B; Nitriles; Phosphorylation; Proto-Oncogene Proteins c-akt; Rats; Rats, Sprague-Dawley; Rats, Zucker; Reverse Transcriptase Polymerase Chain Reaction; Stem Cells; Sulfones; Tumor Necrosis Factor-alpha

The cat has recently been proposed as a valuable model for type 2 diabetes mellitus (T2DM), because feline diabetes shares several similarities with the disease in humans. Impaired beta-cell function, decreased beta-cell mass, insulin resistance that is often related to obesity, and pancreatic amyloid deposition, are among these common features. In this study, and to further develop the cat as a model of T2DM, feline pancreatic islets were isolated and real-time PCR quantification of mRNA transcripts of genes central to beta-cell function and survival established. In particular, mRNA quantification systems were determined for insulin, the insulin enhancer pancreatic duodenal homeobox-1 (PDX-1), the insulin suppressor CCAAT/enhancer binding protein-beta (C/EBPbeta), glucose transporter isoform 2 (GLUT2), Fas receptor, the caspase-8 inhibitor FLIP (FLICE [caspase-8]-inhibitory protein) and two chemokines, interleukin (IL)-8 and monocyte chemoattractant protein-1 (MCP-1). Pancreatic islets were isolated by collagenase digestion from healthy cat donors. Partial feline mRNA sequences were determined for PDX-1, C/EBPbeta, GLUT2 and FLIP using primers identified from conserved regions of human, dog and rat mRNA. These novel and the previously available sequences (insulin, Fas receptor, IL-8 and MCP-1) were used to design feline-specific primers suitable for real-time PCR in isolated pancreatic islets. The adopted protocol of collagenase digestion yielded pancreatic islets that were frequently surrounded by acinar cells. Quantification of mRNA transcripts was simple and reproducible in healthy cats. Characterisation of genes related to insulin signalling in cats will prove useful to better understand the pathogenesis of feline diabetes and possibly of human T2DM.

Topics: Animals; Caspase 8; Cats; Chemokine CCL2; Diabetes Mellitus, Type 2; Disease Models, Animal; Glucose; Humans; Insulin; Insulin-Secreting Cells; Interleukin-8; Islets of Langerhans; Male; Polymerase Chain Reaction; RNA, Messenger; Signal Transduction

The aim of this study was to investigate the effect of periodontal therapy on the circulating concentration of high-sensitivity capsule-reactive protein (hs-CRP), fibrinogen (FIB), interleukin (IL)-4, IL-6, IL-8, IL-10 and tumour necrosis factor-alpha (TNF-alpha) and on the metabolic control in type 2 diabetes mellitus (T2DM) patients.. Twenty-three T2DM patients with chronic periodontitis were enrolled in this study. Periodontal clinical parameters, namely visible plaque index, gingival bleeding index, bleeding on probing, probing depth and clinical attachment levels, were evaluated. Blood samples for plasma were collected and assessed for the levels of hs-CRP, FIB, IL-4, IL-6, IL-8, IL-10 and TNF-alpha. The glycated haemoglobin (HbA(1c)) and fasting plasma glucose were also measured. All parameters were evaluated before and 3 months after non-surgical periodontal therapy.. All clinical parameters were significantly improved 3 months after the periodontal therapy. A univariate comparison showed a tendency towards a decrease of the measured biomarkers, most pronounced for TNF-alpha and FIB, after therapy. Periodontal treatment also reduced HbA(1c) and hs-CRP levels, albeit not significantly.. The clinically successful non-surgical periodontal therapy tended to reduce systemic inflammation and the concentration of some circulating cytokines.

Topics: Adult; Blood Glucose; C-Reactive Protein; Chronic Periodontitis; Cytokines; Dental Plaque Index; Dental Scaling; Diabetes Mellitus, Type 2; Female; Fibrinogen; Follow-Up Studies; Gingival Hemorrhage; Glycated Hemoglobin; Humans; Inflammation Mediators; Interleukin-10; Interleukin-4; Interleukin-6; Interleukin-8; Male; Middle Aged; Periodontal Attachment Loss; Periodontal Index; Periodontal Pocket; Root Planing; Tumor Necrosis Factor-alpha

Type 2 diabetes mellitus (T2D) is predicted by central obesity and circulating adipokines regulating inflammation. We hypothesized that visceral adipose tissue (VAT) in T2D expresses greater levels of proinflammatory molecules. Paired samples of subcutaneous (SAT) and VAT were excised at elective surgery (n = 16, 6 with T2D, n = 8 age- and gender- matched controls). Metabolic parameters were measured in the fasted state: body composition by dual-energy X-ray absorptiometry and insulin action by hyperinsulinemic-euglycemic clamp. Adipose tissue mRNA gene expression was measured by quantitative reverse transcriptase-PCR. Subjects with T2D had higher VAT expression of molecules regulating inflammation (tumor necrosis factor-alpha (TNFalpha), macrophage inflammatory protein (MIP), interleukin-8 (IL-8)). Fasting glucose related to VAT expression of TNFalpha, MIP, serum amyloid A (SAA), IL-1alpha, IL-1beta, IL-8, and IL-8 receptor. Abdominal fat mass was related to VAT expression of MIP, SAA, cAMP response element-binding protein (CREBP), IL-1beta, and IL-8. Insulin action related inversely to VAT complement C3 expression only. There were depot-specific differences in expression of serum T2D predictors: VAT expressed higher levels of complement C3; SAT expressed higher levels of retinol-binding protein-4 (RBP4), adiponectin, and leptin. In summary, VAT in T2D expresses higher levels of adipokines involved in inflammation. VAT expression of these molecules is related to fasting glucose and insulin action. Increased production of these proinflammatory molecules by VAT may explain the links observed between visceral obesity, insulin resistance, and diabetes risk.

Topics: Adipokines; Adult; Aged; Body Mass Index; Chemokine CCL3; Diabetes Mellitus, Type 2; Female; Gene Expression; Humans; Inflammation; Insulin Resistance; Interleukin-8; Intra-Abdominal Fat; Male; Middle Aged; Obesity; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Statistics, Nonparametric; Subcutaneous Fat; Tumor Necrosis Factor-alpha; Waist Circumference

The purpose of this study was to compare intravitreous levels of lipopolysaccharide-binding protein and soluble CD14 (sCD14) between patients with proliferative diabetic retinopathy (PDR) and nondiabetic subjects.. This study included 19 consecutive Type 2 diabetic patients with PDR in whom a vitrectomy was performed. Sixteen vitreous humors from nondiabetic patients matched by age, with idiopathic macular holes, were selected from our vitreous bank and used as a control group. Lipopolysaccharide-binding protein was assessed by enzyme-linked immunosorbent assay and sCD14 by a solid-phase enzyme-amplified sensitive immunoassay.. Lipopolysaccharide-binding protein and sCD14 levels were significantly higher in patients with PDR than in the control group (lipopolysaccharide-binding protein, P < 0.001; sCD14, P < 0.01). After correcting for vitreal proteins, the results remained significantly higher in patients with PDR. No differences in serum levels were observed, and we did not find any correlation between serum and vitreous levels. A direct correlation between lipopolysaccharide-binding protein and sCD14 was detected in the vitreous fluid (r = 0.57; P < 0.001) but not in the plasma. Finally, a significant correlation between intravitreal levels of both lipopolysaccharide-binding protein and sCD14 and interleukin-8 and monocyte chemotactic protein-1 was also detected.. Lipopolysaccharide-binding protein and sCD14 are elevated in the vitreous fluid of patients with PDR and thus may play a role in the innate immune response triggered by the inflammatory injury characteristic of PDR.

Topics: Acute-Phase Proteins; Adult; Aged; Carrier Proteins; Case-Control Studies; Chemokine CCL2; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Enzyme-Linked Immunosorbent Assay; Female; Humans; Interleukin-8; Lipopolysaccharide Receptors; Male; Membrane Glycoproteins; Middle Aged; Retinal Perforations; Vitrectomy; Vitreous Body

Beta cell failure is a crucial component in the pathogenesis of type 2 diabetes. One of the proposed mechanisms of beta cell failure is local inflammation, but the presence of pancreatic islet inflammation in type 2 diabetes and the mechanisms involved remain under debate.. Chemokine and cytokine expression was studied by microarray analysis of laser-capture microdissected islets from pancreases obtained from ten non-diabetic and ten type 2 diabetic donors, and by real-time PCR of human islets exposed to oleate or palmitate at 6 or 28 mmol/l glucose. The cellular source of the chemokines was analysed by immunofluorescence of pancreatic sections from individuals without diabetes and with type 2 diabetes.. Microarray analysis of laser-capture microdissected beta cells showed increased chemokine and cytokine expression in type 2 diabetes compared with non-diabetic controls. The inflammatory response in type 2 diabetes was mimicked by exposure of non-diabetic human islets to palmitate, but not to oleate or high glucose, leading to the induction of IL-1beta, TNF-alpha, IL-6, IL-8, chemokine (C-X-C motif) ligand 1 (CXCL1) and chemokine (C-C motif) ligand 2 (CCL2). Interference with IL-1beta signalling abolished palmitate-induced cytokine and chemokine expression but failed to prevent lipotoxic human islet cell death. Palmitate activated nuclear factor kappaB (NF-kappaB) in human pancreatic beta and non-beta cells, and chemically induced endoplasmic reticulum stress caused cytokine expression and NF-kappaB activation similar to that occurring with palmitate.. Saturated-fatty-acid-induced NF-kappaB activation and endoplasmic reticulum stress may contribute to IL-1beta production and mild islet inflammation in type 2 diabetes. This inflammatory process does not contribute to lipotoxicity ex vivo, but may lead to local chemokine release.

Topics: Aged; Cell Line; Chemokine CCL2; Chemokine CXCL1; Diabetes Mellitus, Type 2; Enzyme-Linked Immunosorbent Assay; Female; Fluorescent Antibody Technique; Humans; In Vitro Techniques; Insulin-Secreting Cells; Interleukin-6; Interleukin-8; Islets of Langerhans; Male; Middle Aged; NF-kappa B; Oligonucleotide Array Sequence Analysis; Palmitates; Polymerase Chain Reaction; Radioimmunoassay; Tumor Necrosis Factor-alpha

Understanding cellular and molecular events in diabetes mellitus will identify new approaches for therapy. Immune system cells are important modulators of chronic inflammation in diabetes mellitus, but the role of B cells is not adequately studied. The aim of this work was to define the function of B cells in diabetes mellitus patients through focus on B cell responses to pattern recognition receptors.. We measured expression and function of Toll-like receptors (TLRs) on peripheral blood B cells from diabetes mellitus patients by flow cytometry and multiplexed cytokine analysis. We similarly analysed B cells from non-diabetic donors and periodontal disease patients as comparative cohorts.. B cells from diabetes mellitus patients secrete multiple pro-inflammatory cytokines, and IL-8 production is significantly elevated in B cells from diabetic patients compared with those from non-diabetic individuals. These data, plus modest elevation of TLR surface expression, suggest B cell IL-8 hyperproduction is a cytokine-specific outcome of altered TLR function in B cells from diabetes mellitus patients. Altered TLR function is further evidenced by demonstration of an unexpected, albeit modest 'anti-inflammatory' function for TLR4. Importantly, B cells from diabetes mellitus patients fail to secrete IL-10, an anti-inflammatory cytokine implicated in inflammatory disease resolution, under a variety of TLR-stimulating conditions. Comparative analyses of B cells from patients with a second chronic inflammatory disease, periodontal disease, indicated that some alterations in B cell TLR function associate specifically with diabetes mellitus.. Altered TLR function in B cells from diabetes mellitus patients increases inflammation by two mechanisms: elevation of pro-inflammatory IL-8 and lack of anti-inflammatory/protective IL-10 production.

Topics: Adult; Aged; B-Lymphocytes; Cytokines; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Flow Cytometry; Humans; Interleukin-10; Interleukin-8; Male; Middle Aged; Toll-Like Receptors

The present study was designed to optimize diagnostics of acute cervical lymphadenitis and adenophlegmona in patients with diabetes. A total of 146 patients with suppurative diseases of the head and the neck were available for examination of whom 63 presented with complicated clinical condition. It was shown that evaluation of the interleukin status (IL-8, IL-10), early diagnosis of systemic inflammatory reaction and compensatory anti-inflammatory response as well as the use of the ultrasound visualization technique make it possible to objectively assess the patient's condition and predict the outcome of the disease taking into consideration effects of hyperglycemia in diabetic patients.

Topics: Acute Disease; Adult; Aged; Biomarkers; Cellulitis; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diagnosis, Differential; Follow-Up Studies; Humans; Interleukin-10; Interleukin-8; Lymphadenitis; Middle Aged; Neck; Retrospective Studies; Young Adult

The aim of this study was to investigate the association between psychosocial variables, biomarker hemoglobin A1C (HbA1C), and immune modulatory cytokine mediators among diabetic patients in marital or committed long-term relationships.. This is a cross-sectional study of adult patients with Type 2 diabetes mellitus (T2DM) presenting at a university-based ambulatory medical clinic. Social/interpersonal constructs were assessed using measures of dyadic adjustment, interpersonal sensitivity and social functioning, and expressed emotion. HbA1c and cytokines were measured from blood samples using standard laboratory tests. Associations of relational systems constructs with biomarkers were assessed using bivariate tests.. Dyadic adjustment was significantly associated with cytokine IL-8. Interpersonal relationship functioning was significantly associated with biomarker HbA1c, and cytokines TNF-alpha, and IL-1ra. Social functioning was significantly correlated with cytokines IL-17, IL-1ra, IL-2r, IL-6, and eotaxin. Depression was significantly correlated with HbA1C.. Although preliminary in nature, findings revealed significant relationships between molecular mediators of the inflammatory and immune systems and variables measuring the relational context patients with T2DM. The initial findings suggest a next step in understanding and exploring the complex but important biopsychosocial pathways in Type 2 DM.

Topics: Adult; Aged; Cytokines; Depressive Disorder; Diabetes Mellitus, Type 2; Expressed Emotion; Family Conflict; Female; Glycated Hemoglobin; Humans; Inflammation; Inflammation Mediators; Interleukin-8; Male; Middle Aged; Personality Inventory; Psychometrics; Self Efficacy; Social Environment; Statistics as Topic

Recently, we identified several flavonoids as inhibitors of the nuclear enzyme poly(ADP-ribose) polymerase (PARP)-1 in vitro and in vivo. PARP-1 is recognized as coactivator of nuclear factor-kappaB and plays a role in the pathophysiology of diseases with low-grade systemic inflammation, such as chronic obstructive pulmonary disease (COPD) and type 2 diabetes (T2D). In this study, we assessed the antiinflammatory effects of flavonoids with varying PARP-1-inhibiting effects in whole blood from male patients with COPD or T2D and healthy men. A total of 10 COPD, 10 T2D patients, and 10 healthy volunteers matched for age and BMI were recruited. Blood from each participant was exposed to 1 microg/L lipopolysaccharide (LPS) over 16 h with or without preincubation with 10 micromol/L of flavone, fisetin, morin, or tricetin. Concentrations of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, -8, and -10 were measured in the supernatant. Preincubation with fisetin and tricetin strongly attenuated LPS-induced increases in concentrations of TNFalpha in blood from COPD patients [mean (+/- SEM): -41 +/- 4% (fisetin) and -31 +/- 4% (tricetin); P < 0.001] and IL-6 in blood from T2D patients [-31 +/- 5% (fisetin) and -29 +/- 6% (tricetin); P < or = 0.001]. Moreover, LPS-induced changes in TNFalpha and IL-6 concentrations were positively correlated with the extent of reduction by fisetin and tricetin. The PARP-1-inhibiting flavonoids fisetin and tricetin were able to attenuate LPS-induced cytokine release from leukocytes of patients with chronic systemic inflammation, indicating a potential application as nutraceutical agents for these patient groups.

Topics: Aged; Chromones; Cytokines; Diabetes Mellitus, Type 2; Enzyme Inhibitors; Flavonoids; Flavonols; Humans; Interleukin-1; Interleukin-10; Interleukin-8; Lipopolysaccharides; Male; Middle Aged; Poly (ADP-Ribose) Polymerase-1; Poly(ADP-ribose) Polymerase Inhibitors; Pulmonary Disease, Chronic Obstructive; Tumor Necrosis Factor-alpha

Inflammatory cytokine genes have been proposed as good candidate genes for conferring susceptibility to diabetic nephropathy. In the present study, we examined the combined effect of multiple alleles of pro inflammatory cytokine genes for determining the risk of nephropathy in type 2 diabetic patients.. Eight single nucleotide polymorphisms (SNPs) of pro-inflammatory cytokine genes (CCL2, TGFB1, IL8, CCR5, and MMP9) were genotyped in two independently ascertained type 2 diabetic cohorts with (DN) and without nephropathy (DM); consisting of patients from North India (n = 495) and South India (n = 188). Genotyping was carried out using PCR, allele specific oligonucleotide-PCR (ASO-PCR), PCR-RFLP and TaqMan allelic discrimination assays and the gene-gene interaction among genetic variants were determined by multi dimensional reduction (MDR) software. Serum high sensitive CRP (hs-CRP) levels were measured by ELISA. The hs-CRP levels were significantly higher in DN as compared to the DM group (p<0.05). The CCL2, IL8, CCR5 and MMP9 polymorphisms were found to be associated with the risk of diabetic nephropathy. Frequency of CCL2 II, IL8 -251AA, CCR5 59029AA and MMP9 279Gln/Gln genotypes were significantly higher in DN than in DM group (p<0.05) and associated with an increased risk of nephropathy in both North and South Indian cohorts. CCR5 DD and IL8 -251AA genotypes were more prevalent in North Indian DN group only. The co-occurrence of risk associated genotypes (II, -2518GG (CCL2), DD (CCR5) and 279Gln/Gln (MMP9) conferred a tenfold increased risk of nephropathy among type 2 diabetics (p<0.0002).. The present study highlights that common variants of inflammatory cytokine genes exert a modest effect on risk of DN and a combination of risk alleles confer a substantial increased risk of nephropathy in type 2 diabetes among Asian Indians.

Topics: Adult; Aged; C-Reactive Protein; Chemokine CCL2; Cytokines; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Ethnicity; Female; Gene Frequency; Genetic Predisposition to Disease; Genotype; Humans; India; Interleukin-8; Male; Matrix Metalloproteinase 9; Middle Aged; Odds Ratio; Polymorphism, Single Nucleotide; Receptors, CCR5; Regression Analysis; Risk Factors; Transforming Growth Factor beta1

Somatostatin plays an important role in the communication between the nervous, endocrine, and immune systems. Although somatostatin or its analogues have been shown to modulate a number of immune functions, their immunomodulatory effects are not uniform and are strongly dependent on the underlying cell system.. The aim of our study was to analyze the immunomodulatory effects of somatostatin and its analogue octreotide on peripheral blood mononuclear cells (PBMC) in vitro. MATERIALS/SUBJECTS:We used lipopolysaccharide-activated cells from normal glucose tolerant (NGT) subjects and from Type 2 diabetes mellitus (T2DM) patients as T2DM is associated with chronic, low-grade inflammation, and measured immune mediator release with multiplex bead-based assays.. Our data showed no statistically significant effects on the secretion of the cytokines interleukin (IL)-1beta, IL-6, IL-10, IL-12, interferon-gamma and tumor necrosis factor-alpha as well as the chemokines IL-8 and monocyte chemoattractant protein (MCP)-1, either on PBMC from T2DM patients or on those from NGT controls. However, a trend towards a dose-dependent biphasic effect was observed for IL- 6, IL-10 and MCP-1 with reduced immune mediator levels at low and increased/unaltered levels at higher somatostatin or octreotide concentrations. These observations could not be explained by interference with cell viability or proliferation.. We could not confirm immunomodulatory properties of somatostatin and octreotide on PBMC. Further analyses are necessary to explain the interaction between neuropeptides and the immune system.

Topics: Adult; Aged; Chemokine CCL2; Chemokines; Cytokines; Diabetes Mellitus, Type 2; Humans; Interleukin-10; Interleukin-12; Interleukin-1beta; Interleukin-6; Interleukin-8; Leukocytes, Mononuclear; Lipopolysaccharides; Middle Aged; Octreotide; Somatostatin

Lactoferrin is an innate immune system protein with multiple beneficial health activities.. To gain insight in the interaction between innate immune system and metabolic disturbances (obesity and insulin resistance), we investigated the relationship between circulating lactoferrin and chronic inflammation-associated insulin resistance according glucose tolerance status in Caucasian population.. Circulating nonstressed lactoferrin (ELISA), metabolic variables, and inflammatory markers were measured in 229 men, 94 with normal (NGT) and 135 with altered glucose tolerance (AGT). Lactoferrin secretion by neutrophil was investigated in whole-blood culture (four young NGT subjects, four older NGT subjects, and four patients with type 2 diabetes) under microbial lipopolysaccharide (LPS) with IL-6 and rosiglitazone treatment. We also tested the lactoferrin action in THP-1 cells under LPS stimulus.. Circulating lactoferrin was significantly decreased in patients with AGT (431.5 +/- 187.5 vs. 493.5 +/- 238.9 ng/ml, P = 0.02). In addition, circulating lactoferrin was negatively associated with hyperglycemia and obesity measures and positively with insulin sensitivity. Lactoferrin was negatively related to inflammatory markers, especially in AGT subjects. In ex vivo experiments, we found a significant decrease in LPS-induced lactoferrin release from neutrophils in subjects with type 2 diabetes. IL-6 coincubation decreased LPS-induced lactoferrin release in NGT subjects (P < 0.001). Finally, rosiglitazone treatment led to increased lactoferrin secretion (398 +/- 193 vs. 280.1 +/- 104.9 ng/ml, P < 0.0001). Lactoferrin decreased nuclear factor-kappabeta activation and IL-6, IL-8, and macrophage chemoattractant protein-1 expression under LPS challenge.. Decreased circulating lactoferrin levels may play a role in chronic low level inflammation-associated insulin resistance.

Topics: Adult; Aged; Biomarkers; Blood Glucose; Chemokine CCL2; Chronic Disease; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Humans; Inflammation; Insulin Resistance; Interleukin-6; Interleukin-8; Lactoferrin; Linear Models; Lipopolysaccharides; Male; Middle Aged; Neutrophils; White People

Although many studies have shown that the metabolic syndrome (MS) and type 2 diabetes mellitus (T2DM) both are associated with chronic inflammatory state and are risk factors for coronary artery disease (CAD), it is still unclear which condition is a more important contributor to the increased production of inflammatory chemokines. The purpose of this study was to assess monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8) levels and their association with insulin resistance and adiponectin concentrations in CAD patients, who were categorized as having T2DM, MS, or neither.. CAD male patients were categorized into three groups: 24 non-obese patients with T2DM (D), 24 obese patients with MS (M) and 24 patients without T2DM or MS (W). 20 healthy subjects were selected as controls (C). Insulin resistance was assessed by the HOMA-IR method, but serum MCP-1, IL-8, and adiponectin levels were measured by xMAP technology.. Serum levels of MCP-1 and IL-8 in D and M groups were increased in comparison with W and C groups (p<0.001, p<0.01), but the increase in the M group was significantly higher than that in the D group (p<0.05, p<0,001), besides MCP-1 and IL-8 concentrations were correlated with HOMA-IR indexes (r=0.52; r=0.49, p<0.0001) and adiponectin levels (r=-0.59, p<0.0001). The M group demonstrated a diminution in the adiponectin level (p<0.01) and pronounced increase of HOMA-IR in comparison with the other three groups (p<0.01).. Obese CAD patients with MS have a more pronounced increase of MCP-1, IL-8 and HOMA-IR and more decreased adiponectin levels than non-obese CAD patients without MS.

Topics: Adiponectin; Adult; Aged; Biomarkers; Chemokine CCL2; Coronary Artery Disease; Diabetes Mellitus, Type 2; Humans; Insulin Resistance; Interleukin-8; Male; Metabolic Syndrome; Middle Aged; Obesity; Risk Factors

Elevated glucose levels impair islet function and survival, and it has been proposed that intraislet expression of IL-1beta contributes to glucotoxicity.. The objective was to investigate IL-1beta mRNA expression in near-pure beta-cells of patients with type 2 diabetes (T2DM) and study the regulation of IL-1beta by glucose in isolated human islets.. Laser capture microdissection was performed to isolate beta-cells from pancreas sections of 10 type 2 diabetic donors and nine controls, and IL-1beta mRNA expression was analyzed using gene arrays and PCR. Cultured human islets and fluorescence-activated cell sorter-purified human beta-cells were used to study the regulation of IL-1beta expression by glucose and IL-1beta.. Gene array analysis of RNA from beta-cells of individuals with T2DM revealed increased expression of IL-1beta mRNA. Real-time PCR confirmed increased IL-1beta expression in six of 10 T2DM samples, with minimal or no expression in nine control samples. In cultured human islets, IL-1beta mRNA and protein expression was induced by high glucose and IL-1beta autostimulation and decreased by the IL-1 receptor antagonist IL-1Ra. The glucose response was negatively correlated with basal IL-1beta expression levels. Autostimulation was transient and nuclear factor-kappaB dependent. Glucose-induced IL-1beta was biologically active and stimulated IL-8 release. Low picogram per milliliter concentrations of IL-1beta up-regulated inflammatory factors IL-8 and IL-6.. Evidence that IL-1beta mRNA expression is up-regulated in beta-cells of patients with T2DM is presented, and glucose-promoted IL-1beta autostimulation may be a possible contributor.

Topics: Autocrine Communication; Cells, Cultured; Diabetes Mellitus, Type 2; Gene Expression Profiling; Glucose; Humans; Insulin-Secreting Cells; Interleukin-1beta; Interleukin-6; Interleukin-8; Islets of Langerhans; NF-kappa B; Oligonucleotide Array Sequence Analysis; RNA, Messenger; Up-Regulation

To evaluate the usefulness of cytokine levels of peripheral blood in diabetic retinopathy (DR), demographic and biochemical parameters including low-density lipoprotein (LDL) diameter as well as cytokine profiles were analyzed in 74 patients with type 2 diabetes mellitus (DM), with DR (n=46) or without DR (n=28). DM duration was longer in the patients with DR than without (p<0.001). Serum glucose (p=0.005) and total cholesterol (p=0.029) levels were higher in DM patients with DR than DM patients without DR. Plasma LDL diameter, interleukin-6 (IL-6), and interleukin-8 (IL-8) showed significant differences among the different degrees of DR severity in analysis of variance (ANOVA) with no definite trend. The risk of DR in DM patients was decreased by an increase of interleukin-10 (IL-10) level [odds ratio (OR)=0.152; confidence interval (CI): 0.028-0.817]. Plasma LDL diameter was smaller and IL-6 and tumor necrosis factor-alpha (TNF-alpha) levels were higher in DM patients with proliferative diabetic retinopathy (PDR) compared to those with non-proliferative diabetic retinopathy (NPDR) (p<0.05). We found that higher IL-10 levels were related to lower risk of DR in DM patients. Levels of IL-6 and TNF-alpha as well as LDL diameter may be helpful in the prediction of PDR in DM patients with DR.

Topics: Adult; Aged; Cholesterol, HDL; Cholesterol, LDL; Cytokines; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Female; Humans; Interleukin-6; Interleukin-8; Male; Middle Aged; Tumor Necrosis Factor-alpha

Adipose tissue-derived cytokines are presumably involved in obesity-associated pathologies including type 2 diabetes and atherosclerosis. Here we studied the lipopolysaccharide (LPS)-induced expression dynamics of tumor necrosis factor-alpha (TNFalpha), interleukin-6 (IL-6), IL-8 and IL-10 in human adipose tissue biopsies, in preadipocyte-derived adipocytes, and in mesenchymal stem cell (MSC)-derived adipocytes. TNFalpha, IL-6, IL-8 and IL-10 secretions by adipose tissue explants were increased 5.5-, 19.5-, 3.5- and 12.5-fold, respectively, by LPS (1 microg/mL) administration. Concordantly, IL-6 and IL-8 release was dose-dependently induced in MSC-derived adipocytes by LPS (>10 pg/mL). In contrast, TNFalpha and IL-10 remained undetectable even at the highest LPS dose (1 microg/mL) after 24h. In MSC- and preadipocyte-derived adipocytes, respectively, exposure to LPS evoked a weak and transient induction of TNFalpha mRNA whereas induction of IL-6 and IL-8 mRNA were pronounced and sustained for at least 24h. Basal glucose uptake, lipolysis and IL-6 mRNA were induced by exogenous TNFalpha (10 ng/mL) but not by IL-6 (10 ng/mL), IL-8 (100 ng/mL) and IL-10 (20 ng/mL). In this adipocyte model TNFalpha induces well known metabolic effects, but together with previous reports these data suggest that inflammation-induced TNFalpha may derive from non-adipocyte sources in adipose tissue, likely to be macrophages.

Topics: Adipocytes; Atherosclerosis; Biopsy; Cells, Cultured; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Gene Expression Regulation; Glucose; Humans; Interleukin-10; Interleukin-6; Interleukin-8; Lipolysis; Lipopolysaccharides; Mesenchymal Stem Cells; Obesity; RNA, Messenger; Time Factors; Tumor Necrosis Factor-alpha

Of late, inflammatory reactions have been considered to play an important part in the development of atherosclerosis. Acute-phase inflammatory reaction, being initially a protective response directed within the homeostasis system towards lesion repair, may by itself due to various factors favor the development of pathological processes. Considering the role played by inflammation in the development of atherosclerosis, and inflammatory activity in obesity and diabetes mellitus (DM), a range of common and interrelated elements of these processes may be marked out. These are acute phase proteins and cytokines. Insulinoresistance, being the common precursor of obesity and DM, plays the key role in vascular lesion. The use of cytokine activity index seems to be a promising method of revealing patients with high risk of atherosclerosis.

Topics: Aged; Coronary Artery Disease; Cytokines; Diabetes Mellitus, Type 2; Female; Humans; Inflammation; Interferon-gamma; Interleukin-6; Interleukin-8; Middle Aged; Obesity; Tumor Necrosis Factor-alpha

The abundance of the adiponectin receptors, AdipoR1 and AdipoR2, and the effects of the antidiabetic adipokine adiponectin in monocytes of normal-weight and overweight controls and type 2 diabetic patients (T2D) were analyzed. AdipoR1 and AdipoR2 mRNAs were increased in monocytes of obese controls and T2D patients when compared to normal-weight controls, and AdipoR1 mRNA positively correlated to AdipoR2 mRNA, the waist to hip ratio and systemic adiponectin. However, AdipoR1 and AdipoR2 proteins were lower in monocytes of T2D compared to normal-weight donors. Induction of IL-6 and IL-8 by adiponectin, an effect involving p38 MAPK, was also reduced in T2D monocytes.

Topics: Adiponectin; Adult; Aged; Diabetes Mellitus, Type 2; Humans; Interleukin-6; Interleukin-8; Male; Middle Aged; Monocytes; p38 Mitogen-Activated Protein Kinases; Receptors, Adiponectin; Signal Transduction; Up-Regulation

The physicochemical and biological characteristics of electronegative low-density lipoprotein (LDL) (LDL(-)) from type 2 diabetic patients (DM2), before and after insulin therapy, were studied.. Total LDL was subfractionated in LDL(+) (native LDL) and LDL(-) by anion-exchange chromatography.. The proportion of LDL(-) was increased in plasma from DM2 patients compared to control subjects (13.8 +/- 4.6% versus 6.1 +/- 2.5, P < 0.05) and was not modified after glycemic optimization (14.0 +/- 5.9%). LDL(-) from DM2 patients presented similar differential characteristics versus LDL(+) than LDL(-) from controls; that is, decreased apoB and oxidizability, and increased triglyceride, nonesterified fatty acids (NEFA), apoE, apoC-III, platelet-activating factor (PAF) acetylhydrolase activity and aggregability. No difference in particle size, antioxidants, malondialdehyde (MDA), fructosamine or glycated low-density lipoprotein (gLDL) was observed between LDL subfractions. Concerning differences between LDL subfractions isolated from DM2 and from control subjects, the former showed increased MDA, fructosamine and gLDL proportion and decreased LDL size and antioxidant content. The only effect of glycemic optimization was a decrease in fructosamine and gLDL in LDL(+) from DM2 subjects. LDL(-) from DM2 patients presented low binding affinity to the low-density lipoprotein receptor (LDLr) in cultured fibroblasts compared to LDL(+) and two- to threefold increased ability to release interleukin-8 (IL-8) and monocyte chemotactic protein 1 (MCP-1) in endothelial cells.. These results suggest that, although nonenzymatic glycosylation and oxidation are increased in type 2 diabetes, these features would not be directly involved in the generation of LDL(-). Moreover, LDL(-) properties suggest that the high proportion observed in plasma could promote accelerated atherosclerosis in DM2 patients through increased residence time in plasma and induction of inflammatory responses in artery wall cells.

Topics: 1-Alkyl-2-acetylglycerophosphocholine Esterase; Aged; Blood Glucose; Cells, Cultured; Chemical Phenomena; Chemistry, Physical; Chemokine CCL2; Chromatography, Ion Exchange; Diabetes Mellitus, Type 2; Electrophoresis, Polyacrylamide Gel; Endothelial Cells; Female; Humans; Interleukin-8; Lipids; Lipoproteins, LDL; Male; Middle Aged; Receptors, LDL

The potential benefits of hyperbaric oxygen therapy (HBOT) have been reported in diabetic patients with foot ulcers. However, the roles of HBOT on wound healing-associated growth factors and inflammatory mediators are not completely understood in diabetes mellitus (DM).. The aim of this study was to investigate the effects of HBOT on circulating cytokines, NO, and insulin-like growth factors (IGF) in patients with type 2 DM.. Serum samples were collected from patients with type 2 DM (n=31) and healthy subjects (n=29) before (baseline) and after the first and third exposure.. Before HBOT, body mass index (BMI) and serum HbA1c were significantly greater, whereas serum IGF-I was significantly lower in diabetic patients compared to healthy subjects (one-way ANOVA, p<0.05). After adjusting for age, gender, and BMI, serum insulin, growth hormone (GH), IGF-II, IGF-binding protein (IGFBP)-1, IGFBP-3, leptin, interleukin (IL)-8, and NO were not significantly altered by HBOT in diabetic patients and healthy subjects (repeated-measures ANOVA). Change in serum insulin (baseline to the third exposure) was a positive predictor of changes in leptin and NO in healthy subjects and diabetic patients, respectively.. Our results suggest that short-term HBOT may not alter the circulating insulin, IGF, leptin, IL-8, and NO levels. In addition, healthy subjects and diabetic patients showed differential responses to HBOT in the relationships of leptin, insulin, and NO. Further studies are needed to clarify the mechanism of HBOT-improved wound healing in diabetic patients with foot ulcers.

Topics: Adult; Aged; Aged, 80 and over; Aging; Body Mass Index; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Growth Hormone; Humans; Hyperbaric Oxygenation; Insulin; Insulin-Like Growth Factor Binding Proteins; Interleukin-8; Leptin; Male; Middle Aged; Nitric Oxide; Regression Analysis; Somatomedins

Monocytes and macrophages play a key role in the progression of atheromatous changes. The peroxisome proliferator-activated receptor gamma (PPAR gamma) can limit macroangiopathy through the control of cytokine transcription. The objectives of this study were to examine the influence of PPAR gamma and its agonist (rosiglitazone) on the TNFalpha, IL-6, IL-8 and IL-10 gene expression in monocytes of patients with diabetic macroangiopathy and to analyse obtained results in context of selected atherogenic factors ant direct indicators of endothelial lesion. TNFalpha, IL-6, IL-8, IL-10 and PPAR gamma gene expression was assessed in peripheral blood monocytes in 45 patients with type 2 diabetes before and following 22 weeks of rosiglitazone therapy (real-time PCR [Applied Biosystems]). As indicators of endothelial lesion, concentration of thrombomodulin (immunoassay [Diagnostica Stago]) and amount of circulating blood endothelial cells (immunofluorescence method with MoAb CLB-HEC19) were determined. Following rosiglitazone therapy, a statistically significant downward tendency of TNFalpha (p=0.026) and IL-8 (p=0.008) gene expression was noted. Before and following rosiglitazone treatment, PPAR gamma, IL-6 and IL-10 gene expression was undetectable in studied monocytes in vivo. In conclusion, TNFalpha and IL-8 play an important role in monocyte atherogenic activity. Rosiglitazone reduces monocyte proinflammatory readiness by influencing the expression of selected atherogenic cytokines (PPAR gamma-independent pathway).

Topics: Adult; Aged; Atherosclerosis; Cohort Studies; Diabetes Mellitus, Type 2; Down-Regulation; Endothelial Cells; Female; Gene Expression Regulation; Humans; Interleukin-8; Male; Middle Aged; Monocytes; Peripheral Vascular Diseases; PPAR gamma; Rosiglitazone; Thiazolidinediones; Tumor Necrosis Factor-alpha

To determine the levels of interleukin 8 (IL-8) in the vitreous of patients with proliferative diabetic retinopathy (PDR).. Observational case-control study.. Vitreous fluid samples were obtained by vitreoretinal surgery from 71 eyes of patients with diabetes mellitus type 2 with PDR and from 17 eyes of nondiabetic patients with a macular hole. PDR was classified as active and inactive and subdivided according to the extent of large-vessel gliotic obliteration. The cytokine levels were measured by cytometric bead array method.. The vitreous levels of IL-8 were significantly higher in patients with PDR in comparison with the control subjects (P < .001) and in patients with higher extent of large vessel gliotic obliteration (P < .001). A vitreous level of IL-8 was not associated with the presence of active PDR.. Increased levels of IL-8 in PDR were associated with a higher extent of large-vessel gliotic obliteration.

Topics: Aged; Case-Control Studies; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Gliosis; Humans; Interleukin-8; Middle Aged; Retinal Neovascularization; Vitreous Body

Diabetes mellitus is associated with an increased incidence of cardiovascular events and microvascular complications. Serum amyloid A (SAA), a HDL apolipoprotein is a risk marker for cardiovascular disease. A permanent increase in SAA plasma levels is observed in diabetics. Because SAA acts on leukocytes, we evaluated whether the synthesis of proinflammatory cytokines and migration of neutrophils and monocytes induced by SAA is affected in diabetics. Cells, isolated from human blood, were cultured in the presence of SAA. TNF-alpha, IL-1beta, IL-8 and IL-1ra levels were measured by ELISA in the culture supernatants and in serum of subjects. Neutrophils and monocytes migration were followed in a chemotaxis chamber. We make the novel observation that neutrophils and monocytes of diabetics are more responsive to SAA for the induction of the proinflammatory cytokine IL-1beta and the proangiogenic and chemotactic protein IL-8. Incremental TNF-alpha production was also found to occur when monocytes were stimulated with SAA. Cell migration was also increased. The increased production of cytokines and increased migration of leukocytes from diabetics in response to SAA may contribute to a sustained accumulation and activation of inflammatory cells in the disease. Accordingly, the hyper-responsiveness of leukocytes to SAA may be relevant to the proinflammatory conditions associated to vascular complications in diabetic patients.

Topics: Adult; Aged; Cell Movement; Cells, Cultured; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Female; Humans; Interleukin 1 Receptor Antagonist Protein; Interleukin-1beta; Interleukin-8; Leukocytes; Male; Middle Aged; Models, Biological; Monocytes; N-Formylmethionine Leucyl-Phenylalanine; Neutrophils; Serum Amyloid A Protein; Tumor Necrosis Factor-alpha

This study evaluated whether the biochemical changes associated with type 2 diabetes modulate the expression of interleukin-1beta, interleukin-6, interleukin-8, and interferon-gamma in sites with chronic periodontitis.. Biopsies were harvested and divided into three groups: group 1, systemically and periodontally healthy subjects (n = 10); group 2, systemically healthy subjects with moderate-to-severe chronic periodontitis (probing depth > 6 mm) (n = 20); and group 3, type 2 diabetic subjects with periodontitis (n = 20). Cytokine levels were assessed in the gingival tissues by enzyme-linked immunosorbent assay analysis.. Data analysis demonstrated that the interleukin-1beta, interleukin-6, interleukin-8, and interferon-gamma levels were higher in the presence of periodontal inflammation than in the absence of inflammation, regardless of systemic status. The interleukin-1beta and interleukin-6 levels were higher in diabetic subjects (group 3) than in systemically healthy patients with comparable types of periodontitis (group 2). No difference was observed for the interleukin-8 and interferon-gamma levels between groups 2 and 3.. Within the limits of this study, it was concluded that type 2 diabetes was associated with increased expression of interleukin-1beta and interleukin-6 in periodontally inflamed tissues of diabetic patients, relative to nondiabetic subjects, and that such overexpression may be involved in the mechanisms by which type 2 diabetes enhances periodontal destruction.

Topics: Adult; Chronic Disease; Dental Plaque; Diabetes Mellitus, Type 2; Enzyme-Linked Immunosorbent Assay; Female; Gingiva; Humans; Interferon-gamma; Interleukin-1beta; Interleukin-6; Interleukin-8; Male; Periodontal Diseases; Periodontal Index

Diabetic endothelial dysfunction was characterized by altered levels of adhesion molecules and cytokines. Aim of our study was to evaluate the effects of diabetic serum on cell-growth and proinflammatory markers in human saphenous vein endothelial cells (HSVEC) from diabetic and non-diabetic patients. Diabetic serum showed (1) complementary proliferative activity for non-diabetic and diabetic HSVEC, (2) unchanged surface expression of adhesion molecules, and (3) elevated levels of sICAM-1 in HSVEC of all donors. The concentration of sVCAM-1 was increased only in diabetic cells. The proinflammatory state of diabetic HSVEC characterized by increased levels of cytokines was compensated. We concluded that even under normoglycemic conditions the serum itself contains critical factors leading to abnormal regulation of inflammation in diabetics. We introduced an in vitro model of diabetes representing the endothelial situation at the beginning of diabetes (non-diabetic cells/diabetic serum) as well as the diabetic chronic state (diabetic cells/diabetic serum).

Topics: Aged; Biological Factors; Cell Proliferation; Cells, Cultured; Chemokine CCL2; Culture Media, Conditioned; Diabetes Mellitus, Type 2; E-Selectin; Endothelial Cells; Endothelium, Vascular; Enzyme-Linked Immunosorbent Assay; Female; Humans; Intercellular Adhesion Molecule-1; Interleukin-6; Interleukin-8; Kinetics; Male; Middle Aged; Serum; Solubility; Vascular Cell Adhesion Molecule-1

To determine the effect of methylglyoxal (MG) on cytokine production by, and apoptosis of, neutrophils from type 2 diabetes mellitus (T2DM) patients.. The levels of plasma MG, cytokines released by isolated neutrophils and the apoptotic status of neutrophils were determined.. The higher level of plasma MG in T2DM patients was correlated positively with glycated hemoglobin levels, fasting plasma glucose levels and urine albumin/creatinine ratios. The basal levels of cytokines released from neutrophils were markedly higher in patients. MG treatment of the neutrophils isolated from diabetic patients either did not alter, or decreased, the production of cytokines. In contrast, MG induced the release of cytokines from neutrophils of non-diabetics. Moreover, the neutrophils from T2DM patients showed a greater proclivity for apoptosis, which was further increased by in vitro MG treatment.. MG stimulated neutrophils to release more cytokines, which might play a role in the development of infection in T2DM.

Topics: Aged; Albuminuria; Anti-Inflammatory Agents; Apoptosis; Blood Glucose; Caspase 3; Creatine; Cytokines; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Enzyme-Linked Immunosorbent Assay; Female; Flow Cytometry; Glycated Hemoglobin; Humans; Interleukin-6; Interleukin-8; Male; Middle Aged; Neutrophils; Nitric Oxide; Pyruvaldehyde; Tumor Necrosis Factor-alpha

Metformin may benefit the macrovascular complications of diabetes independently of its conventional hypoglycemic effects. Accumulating evidence suggests that inflammatory processes participate in type 2 diabetes and its atherothrombotic manifestations. Therefore, this study examined the potential action of metformin as an inhibitor of pro-inflammatory responses in human vascular smooth muscle cells (SMCs), macrophages (Mphis), and endothelial cells (ECs).. Metformin dose-dependently inhibited IL-1beta-induced release of the pro-inflammatory cytokines IL-6 and IL-8 in ECs, SMCs, and Mphis. Investigation of potential signaling pathways demonstrated that metformin diminished IL-1beta-induced activation and nuclear translocation of nuclear factor-kappa B (NF-kappaB) in SMCs. Furthermore, metformin suppressed IL-1beta-induced activation of the pro-inflammatory phosphokinases Akt, p38, and Erk, but did not affect PI3 kinase (PI3K) activity. To address the significance of the anti-inflammatory effects of a therapeutically relevant plasma concentration of metformin (20 micromol/L), we conducted experiments in ECs treated with high glucose. Pretreatment with metformin also decreased phosphorylation of Akt and protein kinase C (PKC) in ECs under these conditions.. These data suggest that metformin can exert a direct vascular anti-inflammatory effect by inhibiting NF-kappaB through blockade of the PI3K-Akt pathway. The novel anti-inflammatory actions of metformin may explain in part the apparent clinical reduction by metformin of cardiovascular events not fully attributable to its hypoglycemic action.

Topics: Anti-Inflammatory Agents; Atherosclerosis; Cell Survival; Cells, Cultured; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Endothelium, Vascular; Glucose; Humans; Hypoglycemic Agents; Interleukin-1; Interleukin-6; Interleukin-8; Macrophages; Metformin; Muscle, Smooth, Vascular; NF-kappa B; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Saphenous Vein

We examined the levels of vitreous chemokines and Sho (Zheng in Chinese) of Chinese-Korean-Japanese medicine in diabetic patients. Patients undergoing vitrectomy were classified into Group 1 (no diabetic retinopathy), Group 2 (diabetic retinopathy with no or a few new vessels), and Group 3 (diabetic retinopathy with many new vessels). The levels of IL-8, MCP-1, MIP-1alpha, MIP-1beta, and RANTES in the vitreous fluid were measured using cytometric bead array method. Sho was determined by the standard diagnostic method of Chinese-Korean-Japanese medicine. Vitreous levels of IL-8 and MCP-1 in Groups 2 and 3 were higher than those in Group 1. MIP-1alpha, MIP-1beta, and RANTES levels in Groups 2 and 3 were almost the same as those in Group 1. The percentage of patients with Keishibukuryo-gan (Guizhifuling-wan in Chinese) sho in Group 3 was higher than that in Group 1. In conclusion, vitreous levels of IL-8 and MCP-1 were high in patients with diabetic vitreoretinopathy. Keishibukuryo-gan sho may be associated with diabetic vitreoretinopathy.

Topics: Aged; Chemokine CCL2; Chemokine CCL3; Chemokine CCL4; Chemokine CCL5; Chemokines; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Female; Humans; Interleukin-8; Macrophage Inflammatory Proteins; Male; Middle Aged; Prospective Studies; Vitrectomy; Vitreoretinopathy, Proliferative; Vitreous Body

Polymorphonuclear neutrophil (PMN) dysfunction is associated with diabetes. We examined the gingival crevicular fluid (GCF) beta-glucuronidase (BG) and interleukin-8 (IL-8) levels of periodontitis patients with and without type 2 diabetes mellitus (DM).. Forty five adults with type 2 DM and 32 adults without DM, both with chronic periodontitis were enrolled. GCF was collected from eight posterior sites in each quadrant, and periodontal parameters were recorded. GCF was assayed for IL-8 by ELISA and BG by a fluorometric assay.. GCF IL-8 was positively correlated with probing depth (PD), and GCF BG but not clinical attachment level (CAL), bleeding on probing (BOP), or plaque index (PI). In contrast, GCF BG was strongly correlated with each of the clinical measures of periodontal disease. Subjects with DM significantly lower levels of both BG (73.0+/-44.8 versus 121.9+/-84.6 pg/sample; p=0.002) and IL-8 (32.1+/-33.1 versus 90.8+/-83.2 pg/sample; p<0.0001) even after adjustments for age, gender, PD, CAL, BOP, and PI. Neither BG nor IL-8 was correlated with HbA1c levels in subjects with DM.. These data suggest that an inadequate local response by PMN, partially explained by an altered chemokine gradient, may contribute to periodontal disease in patients with type 2 DM.

Topics: Adult; Age Factors; Aged; Chronic Disease; Cross-Sectional Studies; Dental Plaque Index; Diabetes Mellitus, Type 2; Female; Gingival Crevicular Fluid; Gingival Hemorrhage; Glucuronidase; Glycated Hemoglobin; Humans; Interleukin-8; Male; Middle Aged; Periodontal Attachment Loss; Periodontal Index; Periodontal Pocket; Periodontitis; Sex Factors

Type II diabetes mellitus (DM) is the most common form of diabetes that constitutes the majority of cases worldwide including Egypt. Chronic elevated glucose level in DM increases monocyte adhesion to aortic endothelial cells (ECs) which is mediated primarily through induction of interleukin-8 (IL-8). This study aimed to investigate the possible role of IL-8 as a potent chemoattractant, pro-inflammatory cytokine in the immuno-inflammatory response of type II diabetic patients in correlation to ferritin and sTFR as markers of glucose homeostasis that characterizes the disease. The current work was conducted on 20 diabetic females and 10 healthy age and sex matching subjects as a group of control. Serum levels of IL-8, ferritin and sTFR were measured in all study subjects under investigation. Results revealed that both serum levels of IL-8 and ferritin were significantly elevated in type II diabetic patients (P = 0.0029 and 0.03 respectively) compared with those of control group while no significant difference was detected between sTFR levels in diabetic patient and control groups. In addition, a significant positive correlation was detected (P = 0.032) between serum levels of IL-8 and sTFR of the studied diabetic patient group. In conclusion, quantitative determination of IL-8, ferritin and sTFR could help in predicting type II diabetes-associated immuno-inflammatory manifestations characterize the micro-and macrovascular disease complications, particularly for high risk populations.

Topics: Adult; Case-Control Studies; Diabetes Mellitus, Type 2; Female; Ferritins; Humans; Interleukin-8; Middle Aged; Receptors, Transferrin

There is much evidence to indicate a role for adipocytokines in insulin resistance and/or type 2 diabetes mellitus. In experimental models, oral salicylates, through their ability to interfere with the nuclear factor-kappa B (NF-kappa B) transcription pathway, have been demonstrated to reverse insulin resistance. The aim of this study was to investigate whether NF-kappa B regulates the release of adipocytokines in human adipose tissue and skeletal muscle. Human sc adipose tissue and skeletal muscle (obtained from normal pregnant women) were incubated in the absence (control) or presence of two NF-kappa B inhibitors sulfasalazine (1.25, 2.5, and 5 mm) and BAY 11-7082 (25, 50, and 100 microm). After an 18-h incubation, the tissues were collected, and NF-kappa B p65 DNA-binding activity and I kappa B kinase (IKK-beta) and insulin receptor-beta protein expression were assessed by ELISA and Western blotting, respectively. The incubation medium was collected, and the release of TNF-alpha, IL-6, IL-8, resistin, adiponectin, and leptin was quantified by ELISA. Treatment of adipose tissue and skeletal muscle with sulfasalazine and BAY 11-7082 significantly inhibited the release of IL-6, IL-8, and TNF-alpha; NF-kappa B p65 DNA-binding activity; and IKK-beta protein expression (P < 0.05, by Newman-Keuls test). There was no effect of sulfasalazine and BAY 11-7082 on resistin, adiponectin, or leptin release. Both sulfasalazine and BAY 11-7082 increased the adipose tissue and skeletal muscle expression of insulin receptor-beta. The data presented in this study demonstrate that the IKK-beta/NF-kappa B transcription pathway is a key regulator of IL-6, IL-8, and TNF-alpha release from adipose tissue and skeletal muscle. Control of the IKK-beta/NF-kappa B pathway may therefore provide an alternative therapeutic strategy for regulating aberrant cytokine release and thereby alleviating insulin resistance in type 2 diabetes mellitus.

Topics: Adiponectin; Adipose Tissue; Adult; Anti-Inflammatory Agents, Non-Steroidal; Blotting, Western; Cell Survival; Cytokines; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Enzyme-Linked Immunosorbent Assay; Female; Gene Expression Regulation; Hormones, Ectopic; Humans; I-kappa B Kinase; Inflammation; Intercellular Signaling Peptides and Proteins; Interleukin-6; Interleukin-8; Leptin; Muscle, Skeletal; NF-kappa B; Nitriles; Pregnancy; Protein Binding; Protein Serine-Threonine Kinases; Receptor, Insulin; Resistin; Sulfasalazine; Sulfones; Time Factors; Tissue Distribution; Transcription, Genetic; Tumor Necrosis Factor-alpha

To determine the intra-vitreous levels of two pro-inflammatory cytokines [interleukin-8 (IL-8), monocyte chemoattractant protein-1 (MCP-1)] and the anti-inflammatory cytokine interleukin-10 (IL-10) in patients with proliferative diabetic retinopathy (PDR). In addition, the relationship between the profile of cytokines and PDR activity has also been evaluated.. The study included 22 consecutive diabetic patients with PDR (4 Type 1 and 18 Type 2) on whom a vitrectomy was performed. Sixteen age-matched non-diabetic patients with other conditions requiring vitrectomy, but in which the retina was not directly affected by neovascularization served as a control group. IL-8, MCP-1 and IL-10 were measured by enzyme-linked immunosorbent assay (ELISA).. The vitreal levels of both IL-8 and MCP-1 were strikingly higher in diabetic patients with PDR in comparison with the control group [173.5 (64-1670) vs. 49 pg/ml (25-145), P < 0.001, and 2171 (388-6155) vs. 438 pg/ml (207-1344), P < 0.001, respectively]. In addition, the vitreous concentrations of IL-8 and MCP-1 were higher in patients with active PDR than in those patients with quiescent PDR [324.5 (80-1670) vs. 173.5 pg/ml (64-487), P = 0.06 and 3596 (1670-6155) vs. 1143 pg/ml (388-2500), P = 0.01, respectively]. However, vitreal levels of IL-10 in diabetic patients were similar to that obtained in the control group [2.89 (1.55-5.50) vs. 2.46 pg/ml (2.2-5.41), P = NS].. The pro-inflammatory cytokines IL-8 and MCP-1 are increased in the vitreous fluid of PDR patients without an increase in the anti-inflammatory cytokine IL-10. In addition, both IL-8 and MCP-1 intra-vitreous levels correlated with PDR activity, thus suggesting that these cytokines may be pathogenically important in PDR.

Topics: Aged; Chemokine CCL2; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Enzyme-Linked Immunosorbent Assay; Female; Humans; Interleukin-10; Interleukin-8; Male; Middle Aged; Vitreous Body

Chemokines are crucial immune mediators in many physiological and pathophysiological conditions. Chemokines have been hypothesized to be involved in macrophage infiltration into adipose tissue in obesity and might therefore play an important role in the development of obesity-related disorders like type 2 diabetes. Out of 1,653 individuals aged 55-74 years participating in a population-based survey in southern Germany (the Kooperative Gesundheitsforschung in der Region Augsburg [KORA] [Cooperative Health Research in the Region of Augsburg] Survey S4, 1999-2001), 236 individuals with type 2 diabetes, 242 subjects with impaired glucose tolerance (IGT), and 244 normoglycemic control subjects were studied for circulating concentrations of interleukin (IL)-8; RANTES (regulated on activation, normal T-cell expressed, and secreted); interferon-gamma-inducible protein-10 (IP-10), and eotaxin. Systemic concentrations of RANTES were higher in individuals with IGT or type 2 diabetes than in control subjects, whereas IL-8 levels were elevated in type 2 diabetic patients only (P < 0.001 for all comparisons). IP-10 and eotaxin were not significantly associated with IGT or type 2 diabetes. Adjustment for age, sex, BMI, hypertension, LDL cholesterol, HDL cholesterol, uric acid, C-reactive protein, and IL-6 did not alter these findings. Our findings indicate that RANTES and IL-8 may be involved in the development of type 2 diabetes independent of metabolic syndrome-related risk factors and of each other. There is no general upregulation of chemokine production in type 2 diabetes, but rather an association of the disease with specific members of the chemokine family.

Topics: Aged; Blood Pressure; Chemokine CCL11; Chemokine CCL5; Chemokine CXCL10; Chemokines, CC; Chemokines, CXC; Cytokines; Diabetes Mellitus, Type 2; Female; Germany; Glucose Intolerance; Health Surveys; Humans; Interleukin-1; Interleukin-8; Male; Middle Aged; Reference Values

We have previously reported increased monocyte adhesion to human aortic endothelial cells (HAECs) cultured in 25 mmol/L glucose (HG) compared with normal glucose (NG) (5.5 mmol/L). In this study, we explored mechanisms that contribute to increased monocyte adhesion by elevated glucose.. We found that HAECs cultured in HG have increased production of the chemokine interleukin-6 (IL-6). We examined whether IL-6 directly modulated monocyte adhesion to EC. Inhibition of IL-6 using a neutralizing antibody significantly reduced glucose-mediated monocyte adhesion by 50%, and addition of IL-6 directly to human EC stimulated monocyte adhesion. PPARalpha has been reported to negatively regulate expression of IL-6 in vascular cells, so we examined PPARalpha-associated signaling in EC. A known PPARalpha agonist, Wy14,643, prevented glucose-mediated IL-6 production by EC and reduced glucose-mediated monocyte adhesion by 40%. HG-cultured HAEC had a 50% reduction in expression of PPARalpha compared with control EC. Primary aortic EC isolated from PPARalpha knockout (KO) mice showed increased monocyte adhesion compared with EC isolated from control mice. PPARalpha KO EC also had increased production of IL-6. Finally, we measured IL-6 levels in diabetic db/db mice and found significant 6-fold elevations in IL-6 levels in db/db EC.. These data indicate that IL-6 production is increased in diabetes and contributes to early vascular inflammatory changes. PPARalpha protects EC from glucose-mediated monocyte adhesion, in part through regulation of IL-6 production.

Topics: Animals; Aorta; Cell Adhesion; Diabetes Mellitus, Type 2; Endothelial Cells; Endothelium, Vascular; Glucose; Humans; Interleukin-6; Interleukin-8; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Mutant Strains; Monocytes; Pioglitazone; Pyrimidines; Receptors, Cytoplasmic and Nuclear; Recombinant Proteins; Thiazolidinediones; Transcription Factors

We have shown that chronic elevated glucose (25 mm) increases monocyte adhesion to human aortic endothelial cells (EC). This increased adhesion is mediated primarily through induction of interleukin (IL)-8 via activation of the transcription factor AP-1 (Srinivasan, S., Yeh, M., Danziger, E. C., Hatley, M. E., Riggan, A. E., Leitinger, N., Berliner, J. A., and Hedrick, C. C. (2003) Circ. Res. 92, 371-377). In the current study, we identified the elements in the AP-1 transcriptional complex that are activated by glucose. These elements include c-Jun, c-Fos, and Fra-1. AP-1 is activated by cellular oxidative stress, and we have reported significant production of ROS by high glucose-cultured cells. We examined signaling pathways upstream of AP-1 in EC that lead to AP-1 activation by HG. EC cultured in 25 mm glucose had a 2-fold increase in p38 phosphorylation compared with control normal glucose-cultured EC. Inhibition of the p38 pathway using 5 microm SB203580 significantly reduced glucose-mediated IL-8 mRNA production by 60%. Furthermore, blocking p38 pathway activation using a dominant-negative p38 construct significantly reduced glucose-mediated monocyte adhesion by 50%. Thus, glucose-stimulated monocyte adhesion is primarily regulated through phosphorylation of p38 with subsequent activation of AP-1, leading to IL-8 production. To study this pathway in the setting of diabetes, we used the db/db mouse. P38 phosphorylation was increased in diabetic db/db mice compared with control mice. We found a dramatic elevation in plasma levels of KC, the mouse ortholog of IL-8 in diabetic db/db mice (1800 +/- 100 pg/ml KC in db/db versus 300 +/- 75 pg/ml in C57BL/6J control mice, p < 0.0001). Inhibition of the p38 pathway in diabetic db/db mice significantly reduced monocyte adhesion by 50%. Taken together, these data indicate that chronic elevated glucose in diabetes activates the p38 MAP kinase pathway to increase inflammatory IL-8 gene induction and monocyte/endothelial adhesion.

Topics: Animals; Base Sequence; Cell Adhesion; Cells, Cultured; Diabetes Mellitus, Type 2; DNA Primers; Endothelium, Vascular; Glucose; Humans; In Vitro Techniques; Interleukin-8; Male; MAP Kinase Signaling System; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Mitogen-Activated Protein Kinases; Models, Biological; Monocytes; p38 Mitogen-Activated Protein Kinases; RNA, Messenger

We have shown that glucose increases monocyte adhesion to human aortic endothelial cells (HAECs) in vitro.1 In the present study, we examined mechanisms by which glucose stimulates monocyte:endothelial interactions. HAECs cultured for 7 days in 25 mmol/L glucose had a 2-fold elevation in interleukin-8 (IL-8) secretion over control cells cultured in 5.5 mmol/L glucose (P<0.001). Use of a neutralizing antibody to IL-8 prevented glucose-mediated monocyte adhesion. Both glucose and IL-8 activated beta1 integrin on the HAEC surface, suggesting that both activate the alpha5beta1 integrin complex on the endothelial surface. The alpha5beta1 integrin complex is important for anchoring connecting segment-1 fibronectin on the HAEC surface for monocyte adhesion. Analysis of the human IL-8 promoter revealed binding sites for NF-kappaB and AP-1 as well as several aligned carbohydrate response elements (also known as E-boxes). Glucose dramatically stimulated IL-8 promoter activity. Using mutated IL-8 promoter constructs and EMSA, we found that the AP-1 element and the glucose-response element were responsible for much of the glucose-mediated activation of IL-8 transcription. Interestingly, inhibition of reactive oxygen species (ROS) production through use of pharmacological uncouplers of the mitochondrial electron transport chain significantly reduced glucose-mediated induction of IL-8 expression. These data indicate that glucose regulates monocyte:endothelial interactions through stimulation of IL-8 and ROS production and activation of the alpha5beta1 integrin complex on HAECs.

Topics: Animals; Binding Sites; Carbonyl Cyanide m-Chlorophenyl Hydrazone; Cell Adhesion; Cells, Cultured; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Endothelium, Vascular; Gene Expression Regulation; Glucose; Humans; Interleukin-8; Mice; Mice, Inbred C57BL; Mice, Obese; Mitochondria; Monocytes; Promoter Regions, Genetic; Reactive Oxygen Species; RNA, Messenger; Thenoyltrifluoroacetone; Transcription Factor AP-1; Uncoupling Agents

Topics: Adult; Aged; Blood Glucose; Body Mass Index; Cytokines; Diabetes Mellitus, Type 2; Female; Humans; Inflammation; Interleukin-18; Interleukin-8; Male; Middle Aged; Reference Values

Levels of platelet-derived microparticles (PMPs), platelet activation markers (P-selectin expressed on, or annexin V binding to, platelets (plt:P-selectin or plt:annexin V, respectively)), chemokines (IL-8, monocyte chemotactic peptide-1 (MCP-1), and regulated on activation normally T-cell expressed and secreted (RANTES)), and soluble P- and E-selectins were compared in peripheral blood from diabetic and control patients in order to develop a better understanding of their potential contribution to diabetic vascular complications. Significant increases were found for PMPs, plt:P-selectin, MCP-1, RANTES and soluble P- and E-selectins in diabetic individuals, whereas IL-8 levels were similar. Furthermore, after ticlopidine treatment, most of these factors receded to baseline levels observed in non-diabetic patients. Our findings indicate that ticlopidine might be able to prevent or reduce vascular complications in diabetic patients.

Topics: Adult; Annexin A5; Blood Platelets; Case-Control Studies; Chemokine CCL2; Chemokine CCL5; Chemokines; Diabetes Mellitus, Type 2; Diabetic Angiopathies; E-Selectin; Female; Humans; Interleukin-8; Male; Middle Aged; P-Selectin; Platelet Activation; Platelet Aggregation Inhibitors; Ticlopidine

Topics: Adolescent; Adult; Aged; Bacteriuria; Cells, Cultured; Cytokines; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Glycosuria; Humans; Interleukin-6; Interleukin-8; Leukocytes; Lipopolysaccharides; Lymphocytes; Middle Aged; Reference Values; Salmonella; Tumor Necrosis Factor-alpha; Urine

Topics: Adult; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Enzyme-Linked Immunosorbent Assay; Female; Glycated Hemoglobin; Humans; Interleukin-8; Male; Middle Aged; Reference Values

Endothelin-1 (ET-1) has been shown to be a potent agonist for monocyte production of the neutrophil chemotactic cytokine interleukin-8 (IL-8). We have shown that diabetic patients demonstrate elevated coronary ET-1 after coronary artery bypass grafting (CABG). We hypothesized that these same diabetic patients would manifest elevated coronary IL-8 and conjugated diene concentrations (an index of reperfusion injury).. Sixteen patients [9 nondiabetics and 7 type II diabetics] underwent nonemergent CABG. The two groups did not differ significantly in preoperative ejection fraction, number of vessels bypassed, or cross-clamp time. Coronary sinus samples were obtained prior to cardioplegic arrest (baseline) and at 1 and 15 min after reperfusion periods A and B (A, reperfusion of native coronaries + LIMA; B, reperfusion of saphenous vein grafts in addition to native coronary system + LIMA). Plasma samples were analyzed for IL-8 (ELISA) and conjugated dienes (spectrophotometry).. Initially after reperfusion, IL-8 in both groups was significantly lower than precardioplegia values. In reperfusion B, only the diabetic group demonstrated a significant increase in IL-8 concentrations at 1 and 15 min compared to nondiabetics. Conjugated diene levels were significantly higher in diabetics at each time point than nondiabetics.. This study demonstrates an early decrease in IL-8 in both groups, most likely related to depressed production secondary to hypothermia. The subsequent elevation in IL-8 only in the diabetic group was seen without concomitant conjugated diene elevation. While no evidence of reperfusion injury was demonstrated in this time frame, the elevation of IL-8 in diabetics after CABG may contribute to later infiltration and associated oxidative damage.

Topics: Alkenes; Cardiopulmonary Bypass; Coronary Vessels; Diabetes Mellitus, Type 2; Enzyme-Linked Immunosorbent Assay; Humans; Interleukin-8; Middle Aged; Myocardial Reperfusion Injury; Spectrophotometry