tretinoin and Diabetes-Mellitus--Type-2

Vitamin A is a fat-soluble essential nutrient obtained from plant- and animal-based sources that has roles in growth, vision, and metabolism. Vitamin A circulates mainly as retinol bound to retinol-binding protein 4 (RBP4), and is delivered to tissues and converted to retinoic acid, which is a ligand for several nuclear receptors. In recent years, aspects of vitamin A metabolism have been under scrutiny with regards to the development of metabolic and lifestyle diseases including cardiovascular disease (CVD), type 2 diabetes mellitus (T2DM), and overweight and obesity in humans. Studies have mainly focused on RBP4 in this context, whereas the major circulating form, retinol, and the major bioactive form, retinoic acid, have been overlooked in this regard until recently. As one of the main roles of RBP4 is to deliver retinol to tissues for biological action, the associations of retinol and retinoic acid with these diseases must also be considered. In this review, we summarize and discuss recent and available evidence from human studies with focus on retinol, retinoic acid, and RBP4 and provide an overview of these crucial components of vitamin A metabolism in CVD, T2DM, and obesity. In summary, retinol was found to be both inversely and positively associated with CVD whereas the associations with T2DM and obesity were less clear. Although only a few studies have been published on retinoic acid, it was inversely associated with CVD. In contrast, serum RBP4 was mostly found to be positively associated with CVD, T2DM, and obesity. At present, it is difficult to ascertain why the reported associations differ depending on the compound under study, but there is a clear imbalance in the literature in disfavor of retinol and retinoic acid, which needs to be considered in future human studies.

Topics: Animals; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Humans; Obesity; Retinol-Binding Proteins, Plasma; Tretinoin; Vitamin A

Mammalian adipose tissue is traditionally categorized into white and brown relating to their function and morphology: while white serves as an energy storage, brown adipose tissue acts as the heat generator maintaining the core body temperature. The most recently identified type of fat, beige adipocyte tissue, resembles brown fat by morphology and function but is developmentally more related to white. The synthesis of beige fat, so-called browning of white fat, has developed into a topical issue in diabetes and metabolism research. This is due to its favorable effect on whole-body energy metabolism and the fact that it can be recruited during adult life. Indeed, brown and beige adipose tissues have been demonstrated to play a role in glucose homeostasis, insulin sensitivity, and lipid metabolism-all factors related to pathogenesis of type 2 diabetes. Many agents capable of initiating browning have been identified so far and tested widely in humans and animal models including in vitro and in vivo experiments. Interestingly, several agents demonstrated to have browning activity are in fact secreted as adipokines from brown and beige fat tissue, suggesting a physiological relevance both in beige adipocyte recruitment processes and in maintenance of metabolic homeostasis. The newest findings on agents driving beige fat recruitment, their mechanisms, and implications on type 2 diabetes are discussed in this review.

Topics: Adipose Tissue, Beige; Adipose Tissue, Brown; Adipose Tissue, White; Animals; Diabetes Mellitus, Type 2; Energy Metabolism; Glucagon-Like Peptide 1; Glucose; Humans; Insulin Resistance; Leptin; Lipid Metabolism; Lipotropic Agents; Melatonin; Natriuretic Peptides; Thermogenesis; Tretinoin

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.

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All-trans Retinoic Acid (atRA), is known as a member of retinoid, and the atRA nano-particle with coated by CaCO3 (nanoegg -atRA), was recently developed as a new drug delivery system (DDS). This nanoparticles stimulated insulin secretion from islets in a glucose-dependent manner at streptozotocin (STZ)-induced diabetes. The stains on pancreas of Wistar rat at STZ induced diabetes, which was subcutaneous administered nanoegg -atRA 6 mg/head/week for 141 days, showed not only the expression of PDX-1 but also the presence of beta cell in islet of Langerhans. Furthermore, the increase of insulin concentration in plasma was also observed. Our data indicate that nanoegg -atRA might contribute to the regeneration of beta cells in vivo, and provide useful information for future therapy of diabetes mellitus.

Topics: Animals; Diabetes Mellitus, Type 2; Insulin; Insulin Secretion; Islets of Langerhans; Male; Nanostructures; Rats; Rats, Wistar; Tretinoin

Recent studies brought adipocyte glyceroneogenesis back to the fore as an important pathway in fatty acid homeostasis and underlined the key role played by cytosolic phosphoenolpyruvate carboxykinase (PEPCK-C) in this pathway. The present review analyses the mechanisms by which a series of hormones and nutrients affect PEPCK-C gene transcription and glyceroneogenesis and describes evidence for disregulation of this pathway in type 2 diabetes.

Topics: Animals; Diabetes Mellitus, Type 2; Fatty Acids; Gene Expression Regulation, Enzymologic; Glycerol; Phosphoenolpyruvate Carboxykinase (GTP); Thiazolidinediones; Tretinoin

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; 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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; 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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; 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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

Diabetic cardiomyopathy is a primary myocardial injury induced by diabetes with complex pathogenesis. In this study, we identify disordered cardiac retinol metabolism in type 2 diabetic male mice and patients characterized by retinol overload, all-trans retinoic acid deficiency. By supplementing type 2 diabetic male mice with retinol or all-trans retinoic acid, we demonstrate that both cardiac retinol overload and all-trans retinoic acid deficiency promote diabetic cardiomyopathy. Mechanistically, by constructing cardiomyocyte-specific conditional retinol dehydrogenase 10-knockout male mice and overexpressing retinol dehydrogenase 10 in male type 2 diabetic mice via adeno-associated virus, we verify that the reduction in cardiac retinol dehydrogenase 10 is the initiating factor for cardiac retinol metabolism disorder and results in diabetic cardiomyopathy through lipotoxicity and ferroptosis. Therefore, we suggest that the reduction of cardiac retinol dehydrogenase 10 and its mediated disorder of cardiac retinol metabolism is a new mechanism underlying diabetic cardiomyopathy.

Topics: Animals; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Diabetic Cardiomyopathies; Heart Diseases; Male; Metabolic Diseases; Mice; Mice, Knockout; Myocytes, Cardiac; Tretinoin; Vitamin A

Topics: Antigens, CD; Antineoplastic Combined Chemotherapy Protocols; Arsenicals; Bone Marrow; Diabetes Mellitus, Type 2; Humans; Idarubicin; Immunophenotyping; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Promyelocytic, Acute; Male; Middle Aged; Neoplasms, Multiple Primary; Remission Induction; Tretinoin

Topics: Antipruritics; Biopsy; Darier Disease; Diabetes Mellitus, Type 2; Diagnosis, Differential; Female; Humans; Hydroxyzine; Hypoglycemic Agents; Insulin; Keratolytic Agents; Middle Aged; Tretinoin; Urea; Vitamin A; Vitamins

Topics: Aging; Animals; Animals, Newborn; Apoptosis; Calcium Signaling; Cell Line; Diabetes Mellitus, Type 2; Female; Gene Expression Regulation; Genes, Reporter; Humans; Hypoglycemic Agents; Insulin; Insulin Secretion; Insulin-Secreting Cells; Islets of Langerhans; Male; Mice; Receptors, G-Protein-Coupled; Recombinant Proteins; Tissue Culture Techniques; Tretinoin

Retinoic acid (RA), an active metabolite of vitamin A (retinol), has been implicated in the regulation of lipid metabolism and hepatic steatosis in animal models. However, the relation between RA and liver histology in patients with nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) is unknown.. This study aimed at examining the association of RA with NAFLD and NASH in Chinese subjects.. Serum RA concentration was determined by ELISA in 41 control subjects, 45 patients with NAFLD, and 38 patients with NASH. The associations of RA with adiposity, serum glucose, lipid profiles, and markers of liver damage were studied. Moreover, both mRNA and protein levels of retinoic X receptor α (RXRα) in the liver were analyzed in subjects with different degrees of hepatic steatosis.. Serum RA concentrations in patients with NAFLD (1.42 ± 0.47 ng/mL) and NASH (1.14 ± 0.26 ng/mL) were significantly lower than those in control subjects (2.70 ± 0.52 ng/mL) (P < 0.01). Furthermore, serum RA concentrations were significantly different between subjects with normal glucose tolerance and those with type 2 diabetes in control [2.87 ± 0.52 (n = 28) vs. 2.32 ± 0.44 ng/mL (n = 13)], NAFLD [1.61 ± 0.37 (n = 29) vs. 1.28 ± 0.41 ng/mL (n = 16)], and NASH [1.35 ± 0.34 (n = 24) vs. 1.07 ± 0.29 ng/mL (n = 14)] groups. In human liver tissue, RXRα mRNA expression was inversely correlated with the exacerbation of hepatic steatosis. Both serum RA concentrations and RXRα mRNA levels were inversely correlated with intrahepatic triglyceride content (r = -0.700, P < 0.001, and r = -0.611, P = 0.002, respectively). Compared with grade 0 severity, the concentration of RXRα protein was lower in more severe grades in patients with NAFLD.. These results show that circulating RA concentrations were lower in subjects with NAFLD and were associated with hepatic lipid metabolism and insulin resistance. This trial was registered at clinicaltrials.gov as NCT01940263.

Topics: Adult; Aged; Asian People; Body Mass Index; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Female; Humans; Insulin Resistance; Lipid Metabolism; Liver; Male; Middle Aged; Non-alcoholic Fatty Liver Disease; Randomized Controlled Trials as Topic; Retinoid X Receptors; RNA, Messenger; Tretinoin; Triglycerides

The aim of this study was to examine the effects of all-trans retinoic acid (ATRA) on diabetic nephropathy.. We measured amounts of urinary albumin excretion (UAE) after administrating ATRA to Otsuka Long-Evans Tokushima Fatty (OLETF) rats. In order to understand the mechanism of action for ATRA, we administrated ATRA to examine its inhibitory action on the production of transforming growth factor-β₁ (TGF-β₁), protein kinase C (PKC), and reactive oxidative stress (ROS) in cultured rat mesangial cells (RMCs).. After 16 weeks of treatment, UAE was lower in the ATRA-treated OLETF rats than in the non-treated OLETF rats (0.07±0.03 mg/mgCr vs. 0.17±0.15 mg/mgCr, p<0.01). After incubation of RMCs in media containing 30 or 5 mM of glucose, treatment with ATRA showed time- and dose-dependent decreases in TGF-β₁ levels and ROS. Moreover, ATRA treatment showed a dose-dependent decrease in PKC expression.. ATRA treatment suppressed UAE and TGF-β₁ synthesis, which was mediated by significant reductions in PKC activity and ROS production. Our results suggest that ATRA has a potential therapeutic role for diabetic nephropathy.

Topics: Animals; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Mesangial Cells; Oxidative Stress; Rats; Rats, Inbred OLETF; Reactive Oxygen Species; Transforming Growth Factor beta1; Tretinoin

The hepatic circadian clock plays a key role in the daily regulation of glucose metabolism, but the precise molecular mechanisms that coordinate these two biological processes are not fully understood. In this study, we identify a novel connection between the regulation of RORγ by the clock machinery and the diurnal regulation of glucose metabolic networks. We demonstrate that particularly at daytime, mice deficient in RORγ exhibit improved insulin sensitivity and glucose tolerance due to reduced hepatic gluconeogenesis. This is associated with a reduced peak expression of several glucose metabolic genes critical in the control of gluconeogenesis and glycolysis. Genome-wide cistromic profiling, promoter and mutation analysis support the concept that RORγ regulates the transcription of several glucose metabolic genes directly by binding ROREs in their promoter regulatory region. Similar observations were made in liver-specific RORγ-deficient mice suggesting that the changes in glucose homeostasis were directly related to the loss of hepatic RORγ expression. Altogether, our study shows that RORγ regulates several glucose metabolic genes downstream of the hepatic clock and identifies a novel metabolic function for RORγ in the diurnal regulation of hepatic gluconeogenesis and insulin sensitivity. The inhibition of the activation of several metabolic gene promoters by an RORγ antagonist suggests that antagonists may provide a novel strategy in the management of metabolic diseases, including type 2 diabetes.

Topics: Animals; Circadian Rhythm; Diabetes Mellitus, Type 2; Gene Expression Regulation; Gluconeogenesis; Glucose; Humans; Insulin; Insulin Resistance; Liver; Mice; Nuclear Receptor Subfamily 1, Group F, Member 3; Tretinoin

Topics: Administration, Topical; Antineoplastic Agents; Diabetes Mellitus, Type 2; Humans; Leukoplakia, Oral; Male; Middle Aged; Treatment Outcome; Tretinoin

To determine the effects of peroxisome proliferator-activated receptor alpha (PPARalpha) and retinoid X receptor (RXR) agonists on insulin action, we investigated the effects of Wy-14643 and 9- cis-retinoic acid (9- cis-RA) on insulin signalling and glucose uptake in human myotubes.. Primary cultures of differentiated human skeletal muscle cells, established from healthy subjects and Type 2 diabetic patients, were used to study the effects of Wy-14643 and 9- cis-RA on the expression and activity of proteins involved in the insulin signalling cascade. Glucose transport was assessed by measuring the rate of [(3)H]2-deoxyglucose uptake.. Wy-14643 and 9- cis-RA increased IRS-2 and p85alpha phosphatidylinositol 3-kinase (PI 3-kinase) mRNA and protein expression in myotubes from non-diabetic and Type 2 diabetic subjects. This resulted in increased insulin stimulation of protein kinase B phosphorylation and increased glucose uptake in cells from control subjects. Myotubes from diabetic patients displayed marked alterations in the stimulation by insulin of the IRS-1/PI 3-kinase pathway. These alterations were associated with blunted stimulation of glucose transport. Treatment with Wy-14643 and 9- cis-RA did not restore these defects but increased the basal rate of glucose uptake.. These results demonstrate that PPARalpha and RXR agonists can directly affect insulin signalling in human muscle cells. They also indicate that an increase in the IRS-2/PI 3-kinase pathway does not overcome the impaired stimulation of the IRS-1-dependent pathway and does not restore insulin-stimulated glucose uptake in myotubes from Type 2 diabetic patients.

Topics: Adult; Diabetes Mellitus, Type 2; Glucose; Humans; Insulin; Insulin Receptor Substrate Proteins; Intracellular Signaling Peptides and Proteins; Muscle Fibers, Skeletal; Muscle, Skeletal; Phosphatidylinositol 3-Kinases; Phosphoproteins; Pyrimidines; Reference Values; Signal Transduction; Tretinoin

To elucidate the effects of retinoic acids (RAs) on adipogenesis and insulin sensitivity, we treated mature adipocytes with two different kinds of RA, 9-cis-RA and all-trans-RA. Both 9-cis- and all-trans-RA inhibited the secretion of leptin. However, the inhibition was significantly decreased at a higher dose of each RA. The inhibitory effect of 9-cis-RA was synergistically enhanced by the addition of rosiglitazone, a synthetic ligand for peroxisome proliferator-activated receptor (PPAR) gamma. 9-cis-RA also leads to adipogenesis in a dose-dependent manner. On the contrary, all-trans-RA does not increase adipogenesis in a dose-dependent manner. To clarify the antidiabetic effects of RA, glucose uptake was assessed by estimating glucose concentrations in the medium. 9-cis-RA reduced glucose levels in the culture media, but all-trans-RA did not. In conclusion, all-trans-RA does not alter adipogenesis and glucose uptake but does inhibit leptin secretion. 9-cis-RA, however, seems to increase both adipogenesis and glucose uptake through activation of the retinoid X receptor/PPARgamma heterodimer.

Topics: Adipocytes; Alitretinoin; Animals; Blood Glucose; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Synergism; Gene Expression Regulation; Glycerol; Isomerism; Leptin; Male; PPAR gamma; Rats; Rats, Sprague-Dawley; Retinoid X Receptors; Rosiglitazone; Thiazolidinediones; Tretinoin

A sensitive HPLC method for simultaneous determination of endogenous levels of all-trans-(ATRA), 13-cis-(13cRA), and 9-cis-retinoic acids (9cRA) was applied to serum samples from healthy volunteers and type II diabetes mellitus patients. Levels of 9cRA (around 0.2 ng/ml in both groups) were below the limit of quantification. The concentrations of ATRA and 13cRA were reliably quantified, and the within-day and between-days variances indicated that they were well maintained with little variation. Concentrations of serum ATRA and 13cRA of diabetic patients (ATRA: 1.76 +/- 0.54 ng/ml; 13cRA: 1.77 +/- 0.39ng/ml, n=13) were rather lower than those of healthy subjects (ATRA: 2.08 +/- 0.53 ng/ml; 13cRA: 2.05 +/- 0.26 ng/ml, n = 18), but the differences were not significant, except for the sum of ATRA and 13cRA (p = 0.033). Interestingly, the serum levels of retinoic acids in diabetic patients correlated positively with the hemoglobin A1c (HbA1c) values (ATRA: r = 0.57, p < 0.05; 13cRA: r = 0.62, p < 0.05). The results warrant further studies on the possible involvement of uncontrolled serum retinoic acids levels in the pathogenesis and/or treatment of diabetes mellitus.

Topics: Adult; Aged; Analysis of Variance; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Isomerism; Middle Aged; Patients; Tretinoin

The nuclear receptor PPARgamma/RXRalpha heterodimer regulates glucose and lipid homeostasis and is the target for the antidiabetic drugs GI262570 and the thiazolidinediones (TZDs). We report the crystal structures of the PPARgamma and RXRalpha LBDs complexed to the RXR ligand 9-cis-retinoic acid (9cRA), the PPARgamma agonist rosiglitazone or GI262570, and coactivator peptides. The PPARgamma/RXRalpha heterodimer is asymmetric, with each LBD deviated approximately 10 degrees from the C2 symmetry, allowing the PPARgamma AF-2 helix to interact with helices 7 and 10 of RXRalpha. The heterodimer interface is composed of conserved motifs in PPARgamma and RXRalpha that form a coiled coil along helix 10 with additional charge interactions from helices 7 and 9. The structures provide a molecular understanding of the ability of RXR to heterodimerize with many nuclear receptors and of the permissive activation of the PPARgamma/RXRbeta heterodimer by 9cRA.

Topics: Alitretinoin; Amino Acid Sequence; Binding Sites; Crystallography; Diabetes Mellitus, Type 2; Dimerization; Drug Design; Histone Acetyltransferases; Humans; Ligands; Models, Molecular; Molecular Sequence Data; Nuclear Proteins; Nuclear Receptor Coactivator 1; Receptors, Cytoplasmic and Nuclear; Receptors, Retinoic Acid; Retinoid X Receptors; Rosiglitazone; Sequence Homology, Amino Acid; Surface Properties; Thiazoles; Thiazolidinediones; Transcription Factors; Tretinoin

Topics: Administration, Topical; Aged; Diabetes Mellitus, Type 2; Female; Humans; Keratolytic Agents; Necrobiosis Lipoidica; Tretinoin