ubiquinone and Insulin-Resistance

Reactive oxygen species (ROS) are produced mainly by mitochondrial respiration and function as signaling molecules in the physiological range. However, ROS production is also associated with the pathogenesis of various diseases, including insulin resistance (IR) and type 2 diabetes (T2D). This review focuses on the etiology of IR and early events, especially mitochondrial ROS (mtROS) production in insulin-sensitive tissues. Importantly, IR and/or defective adipogenesis in the white adipose tissues (WAT) is thought to increase free fatty acid and ectopic lipid deposition to develop into systemic IR. Fatty acid and ceramide accumulation mediate coenzyme Q reduction and mtROS production in IR in the skeletal muscle, while coenzyme Q synthesis downregulation is also involved in mtROS production in the WAT. Obesity-related IR is associated with the downregulation of mitochondrial catabolism of branched-chain amino acids (BCAAs) in the WAT, and the accumulation of BCAA and its metabolites as biomarkers in the blood could reliably indicate future T2D. Transcription factor NF-E2-related factor 2 (Nrf2), which regulates antioxidant enzyme expression in response to oxidative stress, is downregulated in insulin-resistant tissues. However, Nrf2 inducers, such as sulforaphane, could restore Nrf2 and target gene expression and attenuate IR in multiple tissues, including the WAT.

Topics: Diabetes Mellitus, Type 2; Humans; Insulin; Insulin Resistance; NF-E2-Related Factor 2; Oxidative Stress; Reactive Oxygen Species; Ubiquinone

New-onset diabetes has been observed in clinical trials and meta-analyses involving statin therapy. To explain this association, three major mechanisms have been proposed and discussed in the literature. First, certain statins affect insulin secretion through direct, indirect or combined effects on calcium channels in pancreatic β-cells. Second, reduced translocation of glucose transporter 4 in response to treatment results in hyperglycemia and hyperinsulinemia. Third, statin therapy decreases other important downstream products, such as coenzyme Q10, farnesyl pyrophosphate, geranylgeranyl pyrophosphate, and dolichol; their depletion leads to reduced intracellular signaling. Other possible mechanisms implicated in the effect of statins on new-onset diabetes are: statin interference with intracellular insulin signal transduction pathways via inhibition of necessary phosphorylation events and reduction of small GTPase action; inhibition of adipocyte differentiation leading to decreased peroxisome proliferator activated receptor gamma and CCAAT/enhancer-binding protein which are important pathways for glucose homeostasis; decreased leptin causing inhibition of β-cells proliferation and insulin secretion; and diminished adiponectin levels. Given that the magnitude of the risk of new-onset diabetes following statin use remains to be fully clarified and the well-established beneficial effect of statins in reducing cardiovascular risk, statins remain the first-choice treatment for prevention of CVD. Elucidation of the mechanisms underlying the development of diabetes in association with statin use may help identify novel preventative or therapeutic approaches to this problem and/or help design a new generation statin without such side-effects.

Topics: Adipocytes; Adiponectin; Animals; Calcium Channels; Caveolins; Cell Differentiation; Diabetes Mellitus; Dolichols; Glucose Transporter Type 4; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperglycemia; Hyperinsulinism; Insulin; Insulin Resistance; Insulin Secretion; Insulin-Secreting Cells; Ion Channels; Leptin; MicroRNAs; Mitochondrial Proteins; Terpenes; Ubiquinone; Uncoupling Protein 3

Statins are drugs with the unquestionable effectiveness in the reduction of low density lipoprotein cholesterol (LDL-C) and the cardiovascular risk with the acceptable safety profile. On the basis of the above statins are the most common used drugs worldwide. The present review is aimed to discuss the potential mechanisms of statins leading to occurrence of glucose metabolism disturbances through the influence on insulin secretion by the beta-cells of pancreatic islets and the cells' sensitivity on insulin. It might be a results of disadvantageous statin properties connected to the intensification of inflammation and oxidation within the pancreatic islets, and the influence on adipokines secretion by the fat tissue cells. However, it should be emphasized that despite the recommendations of US Food and Drug Administration suggesting to keep caution in connection to potentially prodiabetic statins' properties, this data need to be confirmed in large multicenter clinical trials with properly designed main endpoints.

Topics: Adipokines; Adipose Tissue; Cholesterol, LDL; Diabetes Mellitus; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Insulin; Insulin Resistance; Insulin Secretion; Insulin-Secreting Cells; Pancreatitis; Ubiquinone

Given their essential function in aerobic metabolism, mitochondria are intuitively of interest in regard to the pathophysiology of diabetes. Qualitative, quantitative, and functional perturbations in mitochondria have been identified and affect the cause and complications of diabetes. Moreover, as a consequence of fuel oxidation, mitochondria generate considerable reactive oxygen species (ROS). Evidence is accumulating that these radicals per se are important in the pathophysiology of diabetes and its complications. In this review, we first present basic concepts underlying mitochondrial physiology. We then address mitochondrial function and ROS as related to diabetes. We consider different forms of diabetes and address both insulin secretion and insulin sensitivity. We also address the role of mitochondrial uncoupling and coenzyme Q. Finally, we address the potential for targeting mitochondria in the therapy of diabetes.

Topics: Animals; Blood Glucose; Cell Respiration; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Electron Transport; Humans; Insulin; Insulin Resistance; Insulin Secretion; Insulin-Secreting Cells; Membrane Potential, Mitochondrial; Mice; Mitochondria; Mitochondrial Diseases; Oxidative Stress; Rats; Reactive Oxygen Species; Superoxides; Ubiquinone

Topics: Antioxidants; Coenzymes; Diabetic Angiopathies; DNA Damage; DNA, Mitochondrial; Drug Design; Electron Transport; Humans; Insulin Resistance; Mitochondria; Mitochondrial Diseases; Mutation; Oxidative Stress; Signal Transduction; Superoxides; Thiamine; Transcription Factors; Ubiquinone

Though affecting many thousands of patients, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) should be considered an orphan disease, since the cause remains elusive and no treatment is available that can provide complete cure. There is reasonable insight into the pathogenesis of signs and symptoms, and treatments specifically directed to immunological, inflammatory and metabolic processes offer relief to an increasing number of patients. Particular attention is given to the importance of co-morbidity requiring appropriate therapy. Promising results are obtained by treatment with Metformin, or possibly Momordica charantia extract, which will correct insulin resistance, with Meldonium improving the transportation of glucose into the mitochondria, with sodium dichloroacetate activating pyruvate dehydrogenase, and with nutraceutical support reducing oxidative and inflammatory impairment.

Topics: Adult; Animals; Antiviral Agents; Autoimmune Diseases; Comorbidity; Dichloroacetic Acid; Dietary Supplements; Drug Evaluation, Preclinical; Drug Therapy, Combination; Endocrine System Diseases; Fatigue Syndrome, Chronic; Female; Humans; Infections; Insulin Resistance; Male; Mental Disorders; Methylhydrazines; Middle Aged; Mitochondria; Neuroimaging; Pyruvate Dehydrogenase Complex; Severity of Illness Index; Thiamine; Thioctic Acid; Tomography, Emission-Computed, Single-Photon; Ubiquinone

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in reproductive-age women. The hormonal and metabolic effects of coenzyme Q10 (CoQ10) and/or vitamin E in patients with PCOS have not been studied, to our knowledge.. To evaluate the effects of CoQ10 and/or vitamin E on glucose homeostasis parameters and reproductive hormones in women with PCOS.. Randomized, double-blind, placebo-controlled clinical trial among 86 women with PCOS.. CoQ10 or vitamin E or combination for 8 weeks.. Glucose homeostasis parameters and sex hormone concentrations.. After adjustment for potential confounders, supplementation with CoQ10 alone or in combination with vitamin E, compared with placebo, had significant effects on fasting blood sugar (FBS); vitamin E's effect on FBS was not significant. A significant reduction in homeostasis model assessment of insulin resistance (HOMA-IR) was observed in the CoQ10 and combined groups. CoQ10, vitamin E, and cosupplementation led to decreased serum total testosterone levels (P < 0.001) compared with those of the placebo group. CoQ10 supplementation in combination with vitamin E significantly improved in sex hormone-binding globulin (SHBG) levels compared with other groups (P = 0.008). Linear regression analysis revealed that changes in FBS, insulin, and HOMA-IR were predictors of change in free androgen index (P < 0.05).. CoQ10 with or without vitamin E supplementation among women with PCOS had beneficial effects on serum FBS and insulin levels, as well as HOMA-IR and total testosterone levels. However, only cosupplementation affected SHBG concentrations.

Topics: Adult; Anthropometry; Blood Glucose; Diet; Dietary Supplements; Double-Blind Method; Drug Therapy, Combination; Female; Gonadal Steroid Hormones; Humans; Insulin; Insulin Resistance; Polycystic Ovary Syndrome; Ubiquinone; Vitamin E

Simvastatin is a cholesterol-lowering drug that is prescribed to lower the risk of cardiovascular disease following high levels of blood cholesterol. There is a possible risk of new-onset diabetes mellitus with statin treatment but the mechanisms behind are unknown. Coenzyme Q10 (CoQ10) supplementation has been found to improve glucose homeostasis in various patient populations and may increase muscle glucose transporter type 4 content. Our aim was to investigate if 8 weeks of CoQ10 supplementation can improve glucose homeostasis in simvastatin-treated subjects. Thirty-five men and women in treatment with a minimum of 40 mg of simvastatin daily were randomized to receive either 2 × 200 mg/day of CoQ10 supplementation or placebo for 8 weeks. Glucose homeostasis was investigated with fasting blood samples, oral glucose tolerance test (OGTT) and intravenous glucose tolerance test. Insulin sensitivity was assessed with the hyperinsulinemic-euglycemic clamp. Different indices were calculated from fasting samples and OGTT as secondary measures of insulin sensitivity. A muscle biopsy was obtained from the vastus lateralis muscle for muscle protein analyzes. There were no changes in body composition, fasting plasma insulin, fasting plasma glucose, or 3-h glucose with intervention, but glycated hemoglobin decreased with time. Glucose homeostasis measured as the area under the curve for glucose, insulin, and C-peptide during OGTT was unchanged after intervention. Insulin secretory capacity was also unaltered after CoQ10 supplementation. Insulin sensitivity was unchanged but hepatic insulin sensitivity increased. No changes in muscle GLUT4 content was observed after intervention. CoQ10 supplementation does not change muscle GLUT4 content, insulin sensitivity, or secretory capacity, but hepatic insulin sensitivity may improve.

Topics: Aged; Blood Glucose; C-Peptide; Female; Glucose Tolerance Test; Glucose Transporter Type 4; Glycated Hemoglobin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Insulin; Insulin Resistance; Male; Middle Aged; Simvastatin; Ubiquinone

This study aimed to examine whether administration of coenzyme Q10, an antioxidant, improves insulin resistance in patients with prediabetes. The study design was a pilot single-center, randomized, double-blind, placebo-controlled trial.. This pilot single-center, randomized, double-blind, placebo-controlled trial included a total of 80 adults (aged ≥20 years) with impaired glucose tolerance. After the initial screening visit, subjects were assigned to either the experimental (n = 40) or placebo (n = 40) group via simple randomization. Insulin resistance was represented as the insulin resistance index estimated by homeostasis model assessment (HOMA-IR).. After the 8-week treatment period, the coenzyme group exhibited a significant decrease in the HOMA-IR (P < .001). The free oxygen radical and coenzyme Q10 concentrations were found to correlate significantly (P < .001). However, no significant changes in fasting blood glucose, insulin, and glycated hemoglobin levels were observed in either group. Additionally, no adverse events occurred in either group.. Patients with prediabetes who were administered coenzyme Q10 showed a significant reduction in HOMA-IR values. Therefore, administration of coenzyme Q10 in patients with impaired glucose tolerance may slow the progression from prediabetes to overt diabetes.

Topics: Adult; Aged; Blood Glucose; Double-Blind Method; Female; Humans; Insulin; Insulin Resistance; Male; Middle Aged; Prediabetic State; Ubiquinone; Young Adult

Im Rahmen der vorliegenden Studie sollte der Einfluss des Weichteilschadens auf das klinische Ergebnis nach offener Ellenbogenluxation untersucht werden.. Von Oktober 2008 bis August 2015 wurden insgesamt 230 Patienten mit Ellenbogenluxation behandelt. Diese retrospektive Studie umfasst 21 Fälle von offenen Ellenbogenluxationen. Das Durchschnittsalter der Patienten betrug 49 Jahre alt (20–83 Jahre), 6 Patienten waren weiblich (29%), 15 männlich (71%). Das Bewegungsausmaß des verletzten und unverletzten Ellenbogens wurde erhoben und das funktionelle Ergebnis u. a. mittels Mayo Elbow Performance Score (MEPS), Mayo Wrist Score (MWS) und dem Disability of Arm, Shoulder and Hand (DASH) Score erfasst. Zusätzlich wurden Komplikationen und Revisionsoperationen aufgezeichnet. Der Einfluss des Weichteilschadens (I°/II° offen vs. III° offen) und des Luxationstyps (einfach vs. komplex) auf das klinische Ergebnis wurde analysiert.. Offene Ellenbogenluxationen können mit einem zufriedenstellenden klinischen Ergebnis einhergehen. Insbesondere komplexe offene Ellenbogenluxationen sind jedoch sehr komplikationsbehaftet, wobei neurovaskuläre Komplikationen am häufigsten auftreten.. The current high rate of multidrug-resistant gram-negative bacteria infections among hospitalised patients with cUTIs in the studied area is alarming. Our predictive model could be useful to avoid inappropriate antibiotic treatment and implement antibiotic stewardship policies that enhance the use of carbapenem-sparing regimens in patients at low risk of multidrug-resistance.. The results indicated differential patterns of Inhibition of Return between the High and Low shape/weight based self-worth groups. The High group displayed increased inhibition of return for the shape/weight stimuli relative to control stimuli, while the Low group displayed reduced inhibition of return for the shape/weight stimuli compared to control stimuli. The ED group displayed a similar pattern of results to the High group, but this did not reach significance.. The current findings indicate that young women without an eating disorder who base their self-worth on shape/weight display a pattern of avoidance of shape/weight stimuli that is in direct contrast to those at low risk of developing eating disorders. The possible implications of these specific patterns of inhibition of return across those at varying levels of risk for an eating disorder are discussed along with their implications for intervention approaches.. These results indicated that Sr. An unusually high HbA

Topics: Activities of Daily Living; Acute Disease; Adalimumab; Adaptation, Physiological; Adenosine Triphosphate; Adipose Tissue; Administration, Intravaginal; Adolescent; Adsorption; Adult; Adverse Childhood Experiences; Age Distribution; Age Factors; Aged; Aged, 80 and over; Air Pollution, Indoor; Aldehyde Oxidase; Alginates; Alloys; alpha-Globins; Aluminum Hydroxide; Alveolar Bone Loss; Anaerobiosis; Anesthesia, General; Anesthetics; Animals; Anovulation; Anti-Bacterial Agents; Anti-Infective Agents; Anti-Inflammatory Agents, Non-Steroidal; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Apoptosis; Bacillus cereus; Bacterial Typing Techniques; Bacteroidetes; Base Composition; Biocompatible Materials; Biofilms; Biological Availability; Biological Transport; Biosensing Techniques; Bipolar Disorder; Blood Glucose; Body Mass Index; Bone Regeneration; Boranes; Brachial Artery; Butyric Acid; Candida albicans; Carbon; Carcinoembryonic Antigen; Cell Differentiation; Cell Line, Tumor; Cell Respiration; Cell Survival; Cells, Cultured; Cerebrovascular Circulation; Charcoal; Child; Child Health; China; Chloride Channels; Chlorides; CHO Cells; Chromatography, Liquid; Chromatography, Micellar Electrokinetic Capillary; Chromium; Chronic Disease; Chronic Periodontitis; Circular Dichroism; Cities; Cohort Studies; Comamonadaceae; Comorbidity; Coronary Artery Disease; Corrosion; Cricetinae; Cricetulus; Cross Infection; Cross-Sectional Studies; Crowding; Culture Media; Cytokines; Diabetes Mellitus; Diabetes Mellitus, Type 2; Diabetes, Gestational; Diarylheptanoids; Diclofenac; Disability Evaluation; Diterpene Alkaloids; DNA; DNA Mutational Analysis; DNA, Bacterial; Drug Liberation; Drug Resistance, Multiple, Bacterial; Electrochemical Techniques; Electrodes; Electrolytes; Endothelium, Vascular; Enterococcus faecalis; Epithelial Cell Adhesion Molecule; Epithelial Cells; Erbium; Erythropoietin; Ethanol; Ethylenediamines; Fast Foods; Fatty Acids; Female; Fermentation; Ferric Compounds; Fibroblasts; Flavobacteriaceae; Fluorides; Fluorodeoxyglucose F18; Food Microbiology; Formaldehyde; Furaldehyde; Gamma Cameras; Gene Expression; Geologic Sediments; Glucose Tolerance Test; Glycated Hemoglobin; Glycolipids; Glycosylation; Gracilaria; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Guanine; Health Surveys; HeLa Cells; Hemoglobins, Abnormal; Hexosamines; High Fructose Corn Syrup; High-Intensity Interval Training; Hip Fractures; Hippocampus; HLA-B27 Antigen; Hospitalization; Housing; Humans; Hydrogen-Ion Concentration; Hydrolysis; Hydroxides; Hypercapnia; Hypertension; Hypocreales; Hypromellose Derivatives; Image Processing, Computer-Assisted; Incidence; Indole Alkaloids; Indonesia; Inflammation Mediators; Infrared Rays; Insulin Resistance; Intercalating Agents; Ion Transport; Ionophores; Japan; Kinetics; Kluyveromyces; Letrozole; Linear Models; Lipopolysaccharides; Liposomes; Liver; Lung Diseases; Magnesium Hydroxide; Magnetic Resonance Spectroscopy; Male; Membrane Glycoproteins; Membrane Transport Proteins; Mice, Inbred BALB C; Microbial Sensitivity Tests; Microbial Viability; Microscopy, Electron, Transmission; Middle Aged; Mitochondria; Mitochondria, Muscle; Molecular Docking Simulation; Molecular Structure; Muscle, Skeletal; Mutant Proteins; Mutation; Mutation, Missense; Nanocomposites; Nanoparticles; Neoplasm Recurrence, Local; Neoplastic Cells, Circulating; Nucleic Acid Hybridization; Obesity; Occupational Exposure; Oceans and Seas; Odds Ratio; Organometallic Compounds; Osteogenesis; Ovulation Induction; Oxidation-Reduction; Particle Size; Periodontal Ligament; Permeability; Phaseolus; Phenotype; Philippines; Phosphatidylethanolamines; Phospholipids; Photochemical Processes; Phylogeny; Pichia; Pigmentation; Plant Extracts; Polycystic Ovary Syndrome; Polysaccharides; Postprandial Period; Pregnancy; Pregnancy Rate; Prevalence; Product Surveillance, Postmarketing; Progesterone; Progestins; Protein Engineering; Pseudomonas aeruginosa; Psoriasis; Public Facilities; Rats; Rats, Wistar; Receptors, Thyrotropin; Recombinant Proteins; Reproducibility of Results; Republic of Korea; Retrospective Studies; Rhodobacteraceae; Risk; Risk Assessment; Risk Factors; RNA, Ribosomal, 16S; ROC Curve; Saccharomyces cerevisiae; Salinity; Saliva; Seawater; Seaweed; Sensitivity and Specificity; Sequence Analysis, DNA; Sex Factors; Silver Compounds; Smokers; Social Class; Socioeconomic Factors; Soil Microbiology; Solubility; Soy Foods; Spectrometry, Mass, Electrospray Ionization; Spondylitis, Ankylosing; Staphylococcus aureus; Static Electricity; Steroids; Strontium; Sucrose; Surface Properties; Survival Rate; Sweden; Swine; Synapses; Synchrotrons; Tandem Mass Spectrometry; Tannins; Tea; Temperature; Terpenes; Thalidomide; Thermodynamics; Thiadiazoles; Thyroid Cancer, Papillary; Thyroid Neoplasms; Thyroidectomy; Time Factors; Tissue Distribution; Titanium; Toilet Facilities; Tomography, Emission-Computed, Single-Photon; Treatment Outcome; Ubiquinone; Urinary Tract Infections; Vaginal Creams, Foams, and Jellies; Venezuela; Vitamin K 2; Waist Circumference; Waste Disposal, Fluid; Wastewater; Water Microbiology; Water Pollutants, Chemical; Whole Body Imaging; X-Ray Diffraction; Young Adult; Ytterbium; Yttrium; Yttrium Radioisotopes; Zinc Compounds

The current study was conducted to determine the effects of coenzyme Q10 (CoQ10) supplementation on glycemic control and markers of lipid profiles risk in diabetic hemodialysis (HD) patients.. This randomized, double blind, placebo-controlled clinical trial was performed among 60 diabetic HD patients. Subjects were randomly allocated into two groups to take either 120 mg/day of CoQ10 supplements or placebo (n = 30 each group) for 12 weeks.. After 12 weeks of intervention, CoQ10 supplementation, compared with the placebo, resulted in a significant decrease in serum insulin concentrations (- 2.5 ± 4.0 vs. + 2.8 ± 5.3 µIU/mL, P < 0.001), homeostasis model of assessment-estimated insulin resistance (- 0.9 ± 2.1 vs. + 1.2 ± 3.0, P = 0.002), and significant increase in the quantitative insulin sensitivity check index (+ 0.009 ± 0.01 vs. - 0.02 ± 0.05, P = 0.003). In addition, a trend toward a greater decrease in serum triglycerides (- 5 ± 53 vs. + 17 ± 44, P = 0.078) and VLDL-cholesterol levels (- 0.9 ± 10 vs. + 3 ± 9, P = 0.078) was observed in the CoQ10 group compared to the placebo group. We did not observe any significant effect of CoQ10 supplementation on fasting glucose, HbA1c and other lipid profiles compared with the placebo.. Overall, our study supported that CoQ10 supplementation to diabetic HD patients for 12 weeks had beneficial effects on markers of insulin metabolism, but did not affect fasting glucose, HbA1c, and lipid profiles. Clinical registration http://www.irct.ir : IRCT2016081811763N30.

Topics: Adult; Aged; Blood Glucose; Diabetes Complications; Dietary Supplements; Double-Blind Method; Female; Glycated Hemoglobin; Humans; Insulin; Insulin Resistance; Kidney Failure, Chronic; Lipids; Male; Middle Aged; Renal Dialysis; Triglycerides; Ubiquinone; Vitamins

Limited data are available indicating the effects of coenzyme Q10 (CoQ10) supplementation on metabolic status of patients with metabolic syndrome (MetS).. The present study was conducted to determine the effects of CoQ10 administration on glucose homeostasis parameters, lipid profiles, biomarkers of inflammation and oxidative stress among patients with MetS.. This randomized, double-blind, placebo-controlled trial was performed among 60 overweight or obese and type 2 diabetes mellitus patients with coronary heart disease aged 40-85 years old. Participants were randomly allocated into two groups. Group A (n = 30) received 100 mg CoQ10 supplements and group B (n = 30) received placebo for 8 weeks. Fasting blood samples were taken at the beginning of the study and after 8-week intervention to quantify glucose homeostasis parameters, lipid profiles and biomarkers of inflammation and oxidative stress.. Compared with the placebo, CoQ10 supplementation resulted in a significant reduction in serum insulin levels (-2.1 ± 7.1 vs. +4.1 ± 7.8 µIU/mL, P = 0.002) and homeostasis model of assessment-insulin resistance (-0.7 ± 2.1 vs. +1.0 ± 2.0, P = 0.002) and homeostatic model assessment-beta cell function (-5.9 ± 22.2 vs. +15.9 ± 34.0, P = 0.005). In addition, patients who received CoQ10 supplements had a significant increase in plasma total antioxidant capacity (TAC) concentrations (+26.0 ± 105.0 vs. -162.2 ± 361.8 mmol/L, P = 0.008) compared with the placebo group. However, after adjustment for the baseline levels, age and baseline BMI, the effect on TAC levels (P = 0.08) disappeared. Additionally, compared with the placebo group, a significant positive trends in plasma glutathione (P = 0.06) and a significant reduction in malondialdehyde (P = 0.08) were seen among patients who received CoQ10 supplement. We did not observe any significant changes in fasting plasma glucose, lipid concentrations and inflammatory markers.. Overall, daily intake of 100 mg CoQ10 supplements among patients with MetS for 8 weeks had beneficial effects on serum insulin levels, HOMA-IR, HOMA-B and plasma TAC concentrations.. www.irct.ir : IRCT201502245623N35.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Blood Glucose; Body Mass Index; C-Reactive Protein; Diabetes Mellitus, Type 2; Dietary Supplements; Double-Blind Method; Energy Intake; Glutathione; Homeostasis; Humans; Insulin; Insulin Resistance; Lipids; Malondialdehyde; Metabolic Syndrome; Middle Aged; Nitric Oxide; Obesity; Oxidative Stress; Ubiquinone

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver injury. Chronic exposure to oxidative stress leads to depletion of liver antioxidants and abnormal cytokine production; antioxidant therapy is one of the main therapeutic lines in NAFLD. In the current study we aimed to investigate the effect of coenzyme Q10 (coQ10) therapy on several adipocytokines and insulin resistance in patients with NAFLD.. In the current randomized double-blind placebo controlled trial 44 NAFLD patients were enrolled. After randomization into two groups, 22 patients received 100 mg/day coQ10 capsules and 22 patients received placebo daily for 4 weeks. BMI and WHR were calculated for patients at the beginning and end of the study and blood samples were obtained from the patients to measure serum concentrations of aspartate aminotransferase (AST), alanine aminotransferase (ALT), fasting serum glucose (FSG), insulin resistance (IR), vaspin, chemerin, pentraxin 3 (PTX3) and markers of oxidative stress including total antioxidant capacity (TAC) and malondialdehyde (MDA).. After 4 weeks of coQ10 supplementation, waist circumference (WC) and serum AST and TAC concentrations significantly decreased in intervention group (p <0.05) but no significant changes occurred in placebo-treated group. In stepwise multivariate linear regression model, change in serum FSG was a significant predictor of changes in serum vaspin, chemerin and pentraxin 3 (p <0.001).. The present study showed a potential for coQ10 therapy in improving several anthropometric and biochemical variables in NAFLD. Longer studies with higher doses of coQ10 are required to further evaluate this potential benefit.

Topics: Adipokines; Adult; Alanine Transaminase; Antioxidants; Aspartate Aminotransferases; Biomarkers; Blood Glucose; C-Reactive Protein; Chemokines; Dietary Supplements; Double-Blind Method; Female; Humans; Insulin Resistance; Intercellular Signaling Peptides and Proteins; Male; Middle Aged; Non-alcoholic Fatty Liver Disease; Oxidative Stress; Serpins; Serum Amyloid P-Component; Ubiquinone; Waist Circumference; Young Adult

In a randomised, double-blind trial among patients receiving antihypertensive medication, the effects of the oral treatment with coenzyme Q10 (60 mg twice daily) were compared for 8 weeks in 30 (coenzyme Q10: group A) and 29 (B vitamin complex: group B) patients known to have essential hypertension and presenting with coronary artery disease (CAD). After 8 weeks of follow-up, the following indices were reduced in the coenzyme Q10 group: systolic and diastolic blood pressure, fasting and 2-h plasma insulin, glucose, triglycerides, lipid peroxides, malondialdehyde and diene conjugates. The following indices were increased: HDL-cholesterol, vitamins A, C, E and beta-carotene (all changes P<0.05). The only changes in the group taking the B vitamin complex were increases in vitamin C and beta-carotene (P<0.05). These findings indicate that treatment with coenzyme Q10 decreases blood pressure possibly by decreasing oxidative stress and insulin response in patients with known hypertension receiving conventional antihypertensive drugs.

Topics: Administration, Oral; Antioxidants; Blood Glucose; Blood Pressure; Coenzymes; Coronary Disease; Cytoprotection; Double-Blind Method; Female; Follow-Up Studies; Humans; Hypertension; Insulin; Insulin Resistance; Lipid Peroxides; Male; Malondialdehyde; Middle Aged; Oxidative Stress; Surveys and Questionnaires; Treatment Outcome; Triglycerides; Ubiquinone

Insulin resistance (IR) is a condition in which target cells become insensitive to normal insulin concentrations in order to deliver glucose. The goal of this study was to see if solasodine combined with coenzyme Q10 could help rats with insulin resistance caused by a high-fat diet (HFD) by regulating the expression of IRS-I and PPAR-γ proteins.One of the six groups (n=6) got a conventional diet for 16 weeks as a control (normal), the HFD was given to the other five groups for 16 weeks, which further classified as-one group as HFD control while others treated with pioglitazone (10 mg/kg), coenzyme Q10 (50 mg/kg), solasodine (50 mg/kg) and combination of solasodine and coenzyme Q10i.e. SDQ10 (total 50 mg/kg) for the last 4 weeks orally once daily. Blood and tissue samples were collected by the end of study period for the biochemical and histological studies. As a result, HFD fed rats exhibited a significant increase in food and energy intake, body mass index, kidney and pancreas weight, fasting glucose, glycosylated haemoglobin, insulin level, liver enzyme ALT and AST and decrease antioxidant activity of superoxide dismutase and catalase. HFD received animals also produced a lower level of p-IRS1 and PPAR-y protein expression in western blot analysis. SDQ10 in combination successfully restored the above-mentioned complexity of insulin resistance caused by aHFD. Besides, increasesthe antioxidant activity of superoxide dismutase and catalase and normalized the architecture of kidney, pancreas and adipose tissue as well astreatment with SDQ10 raised the level of p-IRS1 and PPAR-y protein in liver tissue. As a result, supplementing with solasodine and coenzyme Q10 reversed the effect of the HFD on p-IRS1 and PPAR-y protein in liver tissue while also alleviating insulin resistance symptoms.

Topics: Animals; Antioxidants; Blood Glucose; Catalase; Diet, High-Fat; Insulin; Insulin Receptor Substrate Proteins; Insulin Resistance; Insulins; Liver; PPAR gamma; Rats; Solanaceous Alkaloids; Superoxide Dismutase; Ubiquinone

There has been little innovation in identifying novel insulin sensitizers. Metformin, developed in the 1920s, is still used first for most Type 2 diabetes patients. Mice with genetic reduction of p52Shc protein have improved insulin sensitivity and glucose tolerance. By high-throughput screening, idebenone was isolated as the first small molecule 'Shc Blocker'. Idebenone blocks p52Shc's access to Insulin Receptor to increase insulin sensitivity. In this work the avidity of 34 novel idebenone analogs and 3 metabolites to bind p52Shc, and to block the interaction of p52Shc with the Insulin receptor was tested. Our hypothesis was that if an idebenone analog bound and blocked p52Shc's access to insulin receptor better than idebenone, it should be a more effective insulin sensitizing agent than idebenone itself. Of 34 analogs tested, only 2 both bound p52Shc more tightly and/or blocked the p52Shc-Insulin Receptor interaction more effectively than idebenone. Of those 2 only idebenone analog #11 was a superior insulin sensitizer to idebenone. Also, the long-lasting insulin-sensitizing potency of idebenone in rodents over many hours had been puzzling, as the parent molecule degrades to metabolites within 1 h. We observed that two of the idebenone's three metabolites are insulin sensitizing almost as potently as idebenone itself, explaining the persistent insulin sensitization of this rapidly metabolized molecule. These results help to identify key SAR = structure-activity relationship requirements for more potent small molecule Shc inhibitors as Shc-targeted insulin sensitizers for type 2 diabetes.

Topics: Animals; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Insulin; Insulin Resistance; Mice; Mice, Inbred C57BL; Rats; Rats, Sprague-Dawley; Receptor, Insulin; Src Homology 2 Domain-Containing, Transforming Protein 1; Structure-Activity Relationship; Ubiquinone

Topics: Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Insulin Resistance; Precision Medicine; Src Homology 2 Domain-Containing, Transforming Protein 1; Ubiquinone

Insulin resistance in muscle, adipocytes and liver is a gateway to a number of metabolic diseases. Here, we show a selective deficiency in mitochondrial coenzyme Q (CoQ) in insulin-resistant adipose and muscle tissue. This defect was observed in a range of in vitro insulin resistance models and adipose tissue from insulin-resistant humans and was concomitant with lower expression of mevalonate/CoQ biosynthesis pathway proteins in most models. Pharmacologic or genetic manipulations that decreased mitochondrial CoQ triggered mitochondrial oxidants and insulin resistance while CoQ supplementation in either insulin-resistant cell models or mice restored normal insulin sensitivity. Specifically, lowering of mitochondrial CoQ caused insulin resistance in adipocytes as a result of increased superoxide/hydrogen peroxide production via complex II. These data suggest that mitochondrial CoQ is a proximal driver of mitochondrial oxidants and insulin resistance, and that mechanisms that restore mitochondrial CoQ may be effective therapeutic targets for treating insulin resistance.

Topics: Adipocytes; Adipose Tissue; Animals; Ataxia; Humans; Insulin Resistance; Mice; Mitochondria; Mitochondrial Diseases; Muscle Weakness; Muscles; Oxidants; Sensitivity and Specificity; Ubiquinone

When insulin binds insulin receptor, IRS1 signaling is stimulated to trigger the maximal insulin response. p52Shc protein competes directly with IRS1, thus damping and diverting maximal insulin response. Genetic reduction of p52Shc minimizes competition with IRS1, and improves insulin signaling and glucose control in mice, and improves pathophysiological consequences of hyperglycemia. Given the multiple benefits of Shc reduction in vivo, we investigated whether any of 1680 drugs used in humans may function as Shc inhibitors, and thus potentially serve as novel anti-diabetics. Of the 1680, 30 insulin sensitizers were identified by screening in vitro, and of these 30 we demonstrated that 7 bound Shc protein. Of the 7 drugs, idebenone dose-dependently bound Shc protein in the 50-100 nM range, and induced insulin sensitivity and cytoprotection in this same 100 nM range that clinically dosed idebenone reaches in human plasma. By contrast we observe mitochondrial effects of idebenone in the 5,000 nM range that are not reached in human dosing. Multiple assays of target engagement demonstrate that idebenone physically interacts with Shc protein. Idebenone sensitizes mice to insulin in two different mouse models of prediabetes. Genetic depletion of idebenone's target eliminates idebenone's ability to insulin-sensitize in vivo. Thus, idebenone is the first-in-class member of a novel category of insulin-sensitizing and cytoprotective agents, the Shc inhibitors. Idebenone is an approved drug and could be considered for other indications such as type 2 diabetes and fatty liver disease, in which insulin resistance occurs.

Topics: Animals; Cell Line; Cytoprotection; Diabetes Mellitus, Experimental; Drug Repositioning; Female; High-Throughput Screening Assays; Humans; Hypoglycemic Agents; Insulin; Insulin Resistance; Male; Mice, Inbred C57BL; Mice, Knockout; Molecular Docking Simulation; Receptor, Insulin; Src Homology 2 Domain-Containing, Transforming Protein 1; Ubiquinone

This study investigated the anti-diabetic preventive activity of coenzyme Q10 (CoQ10) in a murine model of diet-induced insulin resistance (IR), Psammomys obesus (Po). IR was induced by feeding a standard laboratory diet (SD). CoQ10 oil suspension was orally administered at 10 mg/kg body weight (BW)/day along with SD for 9 months. Anthropometric parameters, namely, total body weight gain (BWG) and the relative weight of white adipose tissue (WAT) were determined. Blood glucose, insulin, quantitative insulin sensitivity check index (QUICKI), total antioxidant status (TAS), iron, malondialdehyde (MDA) and nitrite (NO2 (-)) were evaluated. NO2 (-) level was also assessed in peripheral blood mononuclear cells (PBMCs) culture supernatants. Our results show that CoQ10 supplementation significantly improved blood glucose, insulin, QUICKI, TAS, iron and MDA, but influenced neither NO2 (-) levels nor the anthropometric parameters. These findings support the hypothesis that CoQ10 would exert an anti-diabetic activity by improving both glycaemic control and antioxidant protection. The most marked effect of CoQ10 observed in this study concerns the regulation of iron levels, which may carry significant preventive importance.

Topics: Animals; Antioxidants; Dietary Supplements; Gerbillinae; Insulin Resistance; Iron Overload; Ubiquinone

Metabolic syndrome has become an important health problem, which involves obesity, hyperlipidemia, insulin resistance, and high blood pressure values. The components of metabolic syndrome are all suggested as independent cardiovascular disease risk factors along with high mortality and morbidity rates accompanied by many organ and system complications.. We aimed to determine 8-isoprostane (8-IsoP) and coenzyme Q10 (CoQ10) levels in patients with metabolic syndrome and healthy individuals and demonstrate whether there was any relation between these parameters and metabolic syndrome criteria.. A total of 30 patients (10 male, 20 female) with metabolic syndrome and 20 age-matched healthy individuals (9 male, 11 female) were involved in the study. Body mass index, waist and hip circumferences, systolic and diastolic blood pressures and serum glucose, triglyceride, total cholesterol, high-density lipoprotein cholesterol, insulin, HbA1c, 8-IsoP and CoQ10 levels, and homeostasis model assessment of insulin resistance indexes of all participants were determined.. 8-IsoP levels were significantly increased in metabolic syndrome compared to healthy individuals (P = 0.003), however, there was no significant difference between groups for CoQ10 levels. 8-IsoP levels were positively correlated with waist circumference (r = 0.303, P = 0.032), diastolic blood pressure (r = 0.337, P = 0.017), systolic blood pressure (r = 0.329, P = 0.020) values and total cholesterol levels (r = 0.354, P = 0.012).. We can suggest that the levels of 8-IsoP, which is an indicator of the oxidative stress, increase in metabolic syndrome and this can be associated with high blood pressure and visceral adiposity, which are the components of metabolic syndrome.

Topics: Adult; Aged; Blood Pressure; Body Mass Index; Case-Control Studies; Dinoprost; Female; Humans; Insulin Resistance; Intra-Abdominal Fat; Male; Metabolic Syndrome; Middle Aged; Obesity; Triglycerides; Ubiquinone; Waist Circumference

The fungal product (+)-antroquinonol activates AMP kinase (AMPK) activity in cancer cell lines. The present study was conducted to examine whether chemically synthesized (+)-antroquinonol exhibited beneficial metabolic effects in insulin-resistant states by activating AMPK and inhibiting dipeptidyl peptidase IV (DPP IV) activity.. Effects of (+)-antroquinonol on DPP IV activity were measured with a DPPIV Assay Kit and effects on GLP-1-induced PKA were measured in AR42J cells. Translocation of the glucose transporter 4, GLUT4, induced either by insulin-dependent PI3K/AKT signalling or by insulin-independent AMPK activation, was assayed in differentiated myotubes. Glucose uptake and GLUT4 translocation were assayed in L6 myocytes. Mice with diet-induced obesity were used to assess effects of acute and chronic treatment with (+)-antroquinonol on glycaemic control in vivo.. The results showed that of (+)-antroquinonol (100 μM ) inhibited the DPP IV activity as effectively as the clinically used inhibitor, sitagliptin. The phosphorylation of AMPK Thr(172) in differentiated myotubes was significantly increased by (+)-antroquinonol. In cells simultaneously treated with S961 (insulin receptor antagonist), insulin and (+)-antroquinonol, the combination of (+)-antroquinonol plus insulin still increased both GLUT4 translocation and glucose uptake. Further, (+)-antroquinonol and sitagliptin reduced blood glucose, when given acutely or chronically to DIO mice.. Chemically synthesized (+)-antroquinonol exhibits dual effects to ameliorate insulin resistance, by increasing AMPK activity and GLUT4 translocation, along with inhibiting DPP IV activity.

Topics: AMP-Activated Protein Kinases; Animals; Caco-2 Cells; Cell Line; Cell Line, Tumor; Cyclic AMP-Dependent Protein Kinases; Dipeptidyl Peptidase 4; Dipeptidyl-Peptidase IV Inhibitors; Glucagon-Like Peptide 1; Glucose; Glucose Tolerance Test; Glucose Transporter Type 4; Humans; Insulin Resistance; Mice; Obesity; Rats; Ubiquinone

We report the effects of long-term cola beverage drinking on glucose homeostasis, endocrine pancreas function and morphology in rats.. Wistar rats drank: water (group W), regular cola beverage (group C, sucrose sweetened) or "light" cola beverage (group L, artificially sweetened). After 6 months, 50% of the animals in each group were euthanized and the remaining animals consumed water for the next 6 months when euthanasia was performed. Biochemical assays, insulinemia determination, estimation of insulin resistance (HOMA-IR), morphometry and immunohistochemistry evaluations were performed in pancreas.. Hyperglycemia (16%, p<0.05), CoQ10 (coenzyme-Q10) decrease (-52%,p<0.01), strong hypertriglyceridemia (2.8-fold, p<0.01), hyperinsulinemia (2.4 fold, p<0.005) and HOMA-IR increase (2.7 fold, p<0.01) were observed in C. Group C showed a decrease in number of α cells (-42%, p<0.01) and β cells (-58%, p<0.001) and a moderate increase in α cells' size after wash-out (+14%, p<0.001). Group L showed reduction in β cells' size (-9%, p<0.001) and only after wash-out (L12) a 19% increase in size (p<0.0001) with 35% decrease in number of α cells (p<0.01). Groups C and L showed increase in α/β-cell ratio which was irreversible only in C (α/β = +38% in C6,+30% in C12, p<0.001vs.W6). Regular cola induced a striking increase in the cytoplasmic expression of Trx1 (Thioredoxin-1) (2.25-fold in C6 vs. W6; 2.7-fold in C12 vs. W12, p<0.0001) and Prx2 (Peroxiredoxin-2) (3-fold in C6 vs. W6; 2-fold in C12 vs. W12, p<0.0001). Light cola induced increase in Trx1 (3-fold) and Prx2 (2-fold) after wash-out (p<0.0001, L12 vs. W12).. Glucotoxicity may contribute to the loss of β cell function with depletion of insulin content. Oxidative stress, suggested by increased expression of thioredoxins and low circulating levels of CoQ10, may follow sustained hyperglycemia. A likely similar panorama may result from the effects of artificially sweetened cola though via other downstream routes.

Topics: Analysis of Variance; Animals; Blood Glucose; Carbonated Beverages; Cola; Immunohistochemistry; Insulin Resistance; Islets of Langerhans; Oxidative Stress; Rats; Triglycerides; Ubiquinone

Low birth weight and rapid postnatal growth increases the risk of developing insulin resistance and type 2 diabetes in later life. However, underlying mechanisms and potential intervention strategies are poorly defined. Here we demonstrate that male Wistar rats exposed to a low-protein diet in utero that had a low birth weight but then underwent postnatal catch-up growth (recuperated offspring) had reductions in the insulin signaling proteins p110-β (13% ± 6% of controls [P < .001]) and insulin receptor substrate-1 (39% ± 10% of controls [P < .05]) in adipose tissue. These changes were not accompanied by any change in expression of the corresponding mRNAs, suggesting posttranscriptional regulation. Recuperated animals displayed evidence of a proinflammatory phenotype of their adipose tissue with increased IL-6 (139% ± 8% [P < .05]) and IL1-β (154% ± 16% [P < .05]) that may contribute to the insulin signaling protein dysregulation. Postweaning dietary supplementation of recuperated animals with coenzyme Q (CoQ10) (1 mg/kg of body weight per day) prevented the programmed reduction in insulin receptor substrate-1 and p110-β and the programmed increased in IL-6. These findings suggest that postweaning CoQ10 supplementation has antiinflammatory properties and can prevent programmed changes in insulin-signaling protein expression. We conclude that CoQ10 supplementation represents an attractive intervention strategy to prevent the development of insulin resistance that results from suboptimal in utero nutrition.

Topics: Adipose Tissue; Animals; Female; Gene Expression Profiling; Growth Disorders; Inflammation; Insulin; Insulin Resistance; Lipids; Male; Maternal Exposure; Maternal Nutritional Physiological Phenomena; Mice; MicroRNAs; Oxidative Stress; Phenotype; Rats; Rats, Wistar; Signal Transduction; Ubiquinone

As a nutritional supplement, coenzyme Q10 (CoQ10) was tested previously in several models of diabetes and/or insulin resistance (IR); however, its exact mechanisms have not been profoundly explicated. Hence, the objective of this work is to verify some of the possible mechanisms that underlie its therapeutic efficacy. Moreover, the study aimed to assess the potential modulatory effect of CoQ10 on the antidiabetic action of glimebiride. An insulin resistance/type 2 diabetic model was adopted, in which rats were fed high fat/high fructose diet (HFFD) for 6 weeks followed by a single sub-diabetogenic dose of streptozotocin (35 mg/kg, i.p.). At the end of the 7(th) week animals were treated with CoQ10 (20 mg/kg, p.o) and/or glimebiride (0.5 mg/kg, p.o) for 2 weeks. CoQ10 alone opposed the HFFD effect and increased the hepatic/muscular content/activity of tyrosine kinase (TK), phosphatidylinositol kinase (PI3K), and adiponectin receptors. Conversely, it decreased the content/activity of insulin receptor isoforms, myeloperoxidase and glucose transporters (GLUT4; 2). Besides, it lowered significantly the serum levels of glucose, insulin, fructosamine and HOMA index, improved the serum lipid panel and elevated the levels of glutathione, sRAGE and adiponectin. On the other hand, CoQ10 lowered the serum levels of malondialdehyde, visfatin, ALT and AST. Surprisingly, CoQ10 effect surpassed that of glimepiride in almost all the assessed parameters, except for glucose, fructosamine, TK, PI3K, and GLUT4. Combining CoQ10 with glimepiride enhanced the effect of the latter on the aforementioned parameters.. These results provided a new insight into the possible mechanisms by which CoQ10 improves insulin sensitivity and adjusts type 2 diabetic disorder. These mechanisms involve modulation of insulin and adiponectin receptors, as well as TK, PI3K, glucose transporters, besides improving lipid profile, redox system, sRAGE, and adipocytokines. The study also points to the potential positive effect of CoQ10 as an adds- on to conventional antidiabetic therapies.

Topics: Animals; Diabetes Mellitus, Experimental; Drug Interactions; Glucose Transport Proteins, Facilitative; Hypoglycemic Agents; Insulin Resistance; Liver; Male; Membrane Proteins; Muscle, Skeletal; Nicotinamide Phosphoribosyltransferase; Peroxidase; Phosphatidylinositol 3-Kinases; Protein-Tyrosine Kinases; Rats; Receptor for Advanced Glycation End Products; Receptor, Insulin; Receptors, Adiponectin; Receptors, Immunologic; Transferases; Ubiquinone

The aim of the present study was to investigate whether the aqueous extract of Monascus-fermented grains (MFGEs) enriched with ubiquinones (Coenzyme Qs, CoQ9+CoQ10) alleviates high-fructose (60%) plus high-fat (20%) diet (HFD)-induced hyperglycemia and hepatic oxidative stress in male Sprague-Dawley rats. Animals were fed HFD for 16 weeks and orally administered with MFGEs (300 mg/kg/day) or atorvastatin (20 mg/kg/day) for the last 4 weeks of the study. HFD-fed rats exhibited hyperglycemia, hyperinsulinemia, impaired glucose tolerance, and impaired insulin sensitivity. MFGE treatment prevented the increase in glucose levels and index of insulin resistance in the HFD-induced diabetic rats. A significant decrease in hepatic lipid peroxidation and significant increases in hepatic superoxide dismutase, catalase, and glutathione peroxidase were observed in the MFGE supplemented group. The results suggest that dietary supplementation with MFGEs enriched with CoQs exerts an antidiabetic effect in type 2 diabetic rats by improving insulin resistance and hepatic antioxidant enzymes.

Topics: Administration, Oral; Animals; Antioxidants; Catalase; Diabetes Mellitus, Experimental; Diet, High-Fat; Fermentation; Fructose; Glutathione Peroxidase; Insulin Resistance; Male; Monascus; Oxidative Stress; Rats; Rats, Sprague-Dawley; Superoxide Dismutase; Ubiquinone

Statins significantly reduce cardiovascular events in a broad population of patients with hyperlipidemia. However, a small, but significant risk of new-onset diabetes has been reported in patients treated with statins. The mechanism by which statins cause diabetes has not been elucidated and therefore preventive strategies have yet to be defined.. Our goal was to study the differing effects of a lipophilic (simvastatin) statin, hydrophilic (pravastatin) statin, and ezetimibe on glucose transporter-4 (GLUT4) protein expression in 3T3-L1 adipocytes. We hypothesized that the reductions in GLUT4 protein secondary to statin treatment would be prevented when cells were co-incubated with coenzyme Q10 (CoQ10). GLUT4 protein expression was determined using the In-Cell Western technique. Confluent adipocytes were differentiated using a hormonal cocktail for 3 days; followed by treatment with simvastatin, pravastatin, ezetimibe and CoQ10. Cell morphology was observed after treatment using phase-contrast microscopy.. Treatment with simvastatin (P<0.001) and simvastatin plus ezetimibe (P<0.001) significantly decreased GLUT4 protein expression in the adipocytes compared to control conditions. GLUT4 protein levels were similar to control after treatment with ezetimibe alone (P=0.52) or pravastatin (P=0.32). There was no significant difference (P=0.098) in GLUT4 protein levels after co-treatment with CoQ10 between any of the treatments and control conditions.. Our studies have shown that lipophilic statins (simvastatin) reduce the GLUT4 protein levels in adipocytes, whereas hydrophilic statins (pravastatin) or ezetimibe do not. Co-treatment with CoQ10 appears to prevent the reduction in GLUT4 protein levels caused by simvastatin.

Topics: 3T3-L1 Cells; Adipocytes; Animals; Anticholesteremic Agents; Azetidines; Diabetes Mellitus; Drug Interactions; Ezetimibe; Glucose Transporter Type 4; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Insulin Resistance; Mice; Pravastatin; Simvastatin; Ubiquinone

Glucose tolerance and skeletal muscle coenzyme Q(10) (Q(10)) content, mitochondrial density, and mitochondrial oxidative phosphorylation (OXPHOS) capacity were measured in simvastatin-treated patients (n = 10) and in well-matched control subjects (n = 9).. A prevalent side effect of statin therapy is muscle pain, and yet the basic mechanism behind it remains unknown. We hypothesize that a statin-induced reduction in muscle Q(10) may attenuate mitochondrial OXPHOS capacity, which may be an underlying mechanism.. Plasma glucose and insulin concentrations were measured during an oral glucose tolerance test. Mitochondrial OXPHOS capacity was measured in permeabilized muscle fibers by high-resolution respirometry in a cross-sectional design. Mitochondrial content (estimated by citrate synthase [CS] activity, cardiolipin content, and voltage-dependent anion channel [VDAC] content) as well as Q(10) content was determined.. Simvastatin-treated patients had an impaired glucose tolerance and displayed a decreased insulin sensitivity index. Regarding mitochondrial studies, Q(10) content was reduced (p = 0.05), whereas mitochondrial content was similar between the groups. OXPHOS capacity was comparable between groups when complex I- and complex II-linked substrates were used alone, but when complex I + II-linked substrates were used (eliciting convergent electron input into the Q intersection [maximal ex vivo OXPHOS capacity]), a decreased (p < 0.01) capacity was observed in the patients compared with the control subjects.. These simvastatin-treated patients were glucose intolerant. A decreased Q(10) content was accompanied by a decreased maximal OXPHOS capacity in the simvastatin-treated patients. It is plausible that this finding partly explains the muscle pain and exercise intolerance that many patients experience with their statin treatment.

Topics: Blood Glucose; Case-Control Studies; Cell Respiration; Electron Transport; Electron Transport Complex I; Electron Transport Complex II; Glucose Intolerance; Glucose Tolerance Test; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Insulin Resistance; Male; Middle Aged; Mitochondria, Muscle; Muscle Fibers, Skeletal; Muscle, Skeletal; Oxidative Phosphorylation; Simvastatin; Ubiquinone

To determine plasma CoQ(10) concentration in the course of gestational diabetes mellitus.. The assessment was provided longitudinally during the third trimester of pregnancy in 40 women with gestational diabetes mellitus (GDM) and 40 normal controls. CoQ(10) was measured with the HPLC method. CoQ(10) results were also normalized to plasma cholesterol concentration (nmoles/mmoles). Plasma samples were collected longitudinally throughout the third trimester.. No statistically significant difference of plasma CoQ(10)/cholesterol levels between GDM patients and controls at 28-32 and 32-36 weeks of gestation, this difference was significant in late pregnancy (36-40 weeks), similarly, in the same gestational period, there was an increased level of HOMA-IR as index of insulin resistance ORAC as index of oxidative stress.. Since coenzyme Q(10) is believed to be an important cellular antioxidant defence, higher levels of CoQ(10) in GDM patients may be a compensatory mechanism, in response to an activated oxidative stress, probably associated to hyperglycaemia and insulin resistance.

Topics: Adult; Biomarkers; Blood Glucose; Case-Control Studies; Cholesterol; Chromatography, High Pressure Liquid; Diabetes, Gestational; Female; Humans; Insulin; Insulin Resistance; Italy; Longitudinal Studies; Oxidative Stress; Pregnancy; Pregnancy Trimester, Third; Ubiquinone

Diets high in saturated fat and fructose have been implicated in the development of obesity and nonalcoholic steatohepatitis (NASH) in humans. We hypothesized that mice exposed to a similar diet would develop NASH with fibrosis associated with increased hepatic oxidative stress that would be further reflected by increased plasma levels of the respiratory chain component, oxidized coenzyme Q9 ((ox)CoQ9). Adult male C57Bl/6 mice were randomly assigned to chow, high-fat (HF), or high-fat high-carbohydrate (HFHC) diets for 16 weeks. The chow and HF mice had free access to pure water, whereas the HFHC group received water with 55% fructose and 45% sucrose (wt/vol). The HFHC and HF groups had increased body weight, body fat mass, fasting glucose, and were insulin-resistant compared with chow mice. HF and HFHC consumed similar calories. Hepatic triglyceride content, plasma alanine aminotransferase, and liver weight were significantly increased in HF and HFHC mice compared with chow mice. Plasma cholesterol (P < 0.001), histological hepatic fibrosis, liver hydroxyproline content (P = 0.006), collagen 1 messenger RNA (P = 0.003), CD11b-F4/80+Gr1+ monocytes (P < 0.0001), transforming growth factor beta1 mRNA (P = 0.04), and alpha-smooth muscle actin messenger RNA (P = 0.001) levels were significantly increased in HFHC mice. Hepatic oxidative stress, as indicated by liver superoxide expression (P = 0.002), 4-hydroxynonenal, and plasma (ox)CoQ9 (P < 0.001) levels, was highest in HFHC mice.. These findings demonstrate that nongenetically modified mice maintained on an HFHC diet in addition to developing obesity have increased hepatic ROS and a NASH-like phenotype with significant fibrosis. Plasma (ox)CoQ9 correlated with fibrosis progression. The mechanism of fibrosis may involve fructose inducing increased ROS associated with CD11b+F4/80+Gr1+ hepatic macrophage aggregation, resulting in transforming growth factor beta1-signaled collagen deposition and histologically visible hepatic fibrosis.

Topics: Animals; Body Composition; Collagen; Dietary Carbohydrates; Dietary Fats; Disease Models, Animal; Fatty Liver; Fructose; Insulin Resistance; Liver; Liver Cirrhosis; Male; Mice; Mice, Inbred C57BL; Obesity; Reactive Oxygen Species; Trans Fatty Acids; Transforming Growth Factor beta; Ubiquinone

We recently reported insulin resistance in adult offspring of obese C57BL/6J mice. We have now evaluated whether parameters of skeletal muscle structure and function may play a role in insulin resistance in this model of developmental programming. Obesity was induced in female mice by feeding a highly palatable sugar and fat-rich diet for 6 wk prior to pregnancy, and during pregnancy and lactation. Offspring of obese dams were weaned onto standard laboratory chow. At 3 mo of age, skeletal muscle insulin signaling protein expression, mitochondrial electron transport chain activity (ETC), muscle fiber type, fiber density, and fiber cross-sectional area were compared with that of offspring of control dams weaned onto the chow diet. Female offspring of obese dams demonstrated decreased skeletal muscle expression of p110beta, the catalytic subunit of PI3K (P < 0.01), as well as reduced Akt phosphorylation at Serine residue 473 compared with control offspring. Male offspring of obese dams demonstrated increased skeletal muscle Akt2 and PKCzeta expression (P < 0.01; P < 0.001, respectively). A decrease in mitochondrial-linked complex II-III was observed in male offspring of obese dams (P < 0.01), which was unrelated to CoQ deficiency. This was not observed in females. There were no differences in muscle fiber density between offspring of obese dams and control offspring in either sex. Sex-related alterations in key insulin-signaling proteins and in mitochondrial ETC may contribute to a state of insulin resistance in offspring of obese mice.

Topics: Animal Nutritional Physiological Phenomena; Animals; Body Weight; Class I Phosphatidylinositol 3-Kinases; Disease Models, Animal; Electron Transport Complex II; Electron Transport Complex III; Female; Glucose Transporter Type 4; Insulin; Insulin Receptor Substrate Proteins; Insulin Resistance; Male; Maternal Nutritional Physiological Phenomena; Mice; Mice, Inbred C57BL; Mitochondria, Muscle; Muscle Fibers, Skeletal; Obesity; Phosphatidylinositol 3-Kinases; Phosphorylation; Pregnancy; Prenatal Exposure Delayed Effects; Protein Kinase C; Proto-Oncogene Proteins c-akt; Quadriceps Muscle; Receptor, Insulin; Sex Factors; Signal Transduction; Ubiquinone

Biliopancreatic diversion (BPD) is a surgical procedure performed in patients with untreatable obesity and insulin resistance. The demonstrated metabolic and hormonal results of this procedure include the reversal of insulin resistance; an increase in diet-induced thermogenesis; and modifications of gut hormones, such as gastrin, enteroglucagon, neurotensin, and cholecystokinin. On the other hand, obesity is a condition of increased oxidative stress; however, few studies have investigated antioxidant systems in obese persons with BPD. To evaluate the metabolic status and antioxidant systems in such patients, we studied a group of 11 morbidly obese patients, aged 28 to 62 years, with a mean body mass index (BMI) of 54.71 +/- 2.52 kg/m(2), before and after successful BPD (mean post-BPD BMI, 44.68 +/- 1.51 kg/m(2)). A control group composed of 10 slightly overweight women, with a mean BMI of 28.5 +/- 0.72 kg/m(2), was also studied. Coenzyme Q(10) (CoQ(10)) levels (also normalized for cholesterol levels) and total antioxidant capacity in blood plasma were assessed in these populations. The most striking datum was the extremely low level of CoQ(10) in postoperative period (0.34 +/- 0.16 vs 0.66 +/- 0.09 mug/mL, P = .04); also, the data corrected for cholesterol levels presented the same pattern, with a more marked significance (152.46 +/- 11.13 vs 186.4 +/- 17.98 nmol/mmol, P = .001). This could be due to lipid malabsorption after surgery. In fact, the pre-BPD data present all the metabolic and hormonal characteristics of severe obesity; and after BPD, there was a net improvement in the metabolic parameters. The first pathophysiologic phenomenon seems to be lipid malabsorption that has been argued to be the cause of insulin resistance reversion. This metabolic interpretation is also confirmed by the absence of significant variations of total antioxidant capacity (57.5 +/- 5.3 vs 66 +/- 5.3). The mechanisms of these phenomena remain to be established. These data suggest the importance of correcting postsurgical metabolic complications, in these clinical populations, with CoQ(10) supplementation.

Topics: Adult; Antioxidants; Benzothiazoles; Biliopancreatic Diversion; Blood Glucose; Cholesterol; Female; Humans; Insulin; Insulin Resistance; Male; Middle Aged; Obesity, Morbid; Statistics, Nonparametric; Sulfonic Acids; Thiazoles; Triglycerides; Ubiquinone; Uric Acid

The aim of the present study was to examine the systemic parameters of oxidative stress and antioxidants in patients with nonalcoholic fatty liver disease and investigate the relationship between these parameters and clinical and biochemical outcomes.. Fifty-one male patients with nonalcoholic fatty liver disease (group I), 30 age-matched and body mass index (BMI)-matched healthy male subjects, and 30 age-matched male patients with chronic viral hepatitis (group II) were enrolled in the study.. Increased systemic levels of malondialdehyde and depletion of antioxidants such as coenzyme Q10, CuZn-superoxide dismutase, and catalase activity were observed in group I. Coenzyme Q10 and CuZn-superoxide dismutase correlated negatively with increasing necroinflammatory activity and fibrosis. Body fat was negatively associated with plasma coenzyme Q10 levels, while an inverse association was found between plasma catalase levels and TG. However, LDL was positively associated with plasma malondialdehyde levels. CuZn-superoxide dismutase levels were negatively associated with glucose, insulin, and HOMA-IR. In addition, the levels of CuZn-superoxide dismutase correlated significantly in a negative manner with BMI.. Our results concerning correlations suggest that disturbances in BMI, body fat, and lipid metabolism may contribute to altered oxidative status in NAFLD, and insulin resistance may be related to decreased antioxidants in NAFLD as well as products of lipid peroxidation. However, although our results suggest interesting correlations, this different mostly "weak" relationships must be taken with caution.

Topics: Adult; Antioxidants; Biomarkers; Body Composition; Body Mass Index; Catalase; Coenzymes; Complement C3a; Fatty Liver; Hepatitis B, Chronic; Hepatitis C, Chronic; Humans; Insulin Resistance; Lipid Peroxidation; Liver; Liver Cirrhosis; Male; Malondialdehyde; Middle Aged; Oxidative Stress; Reference Values; Statistics as Topic; Superoxide Dismutase; Ubiquinone

Childhood obesity is associated with lower plasma levels of lipophilic antioxidants which may contribute to a deficient protection of low-density lipoproteins (LDL). An increased plasma level of oxidized LDL in obese people with insulin resistance has been demonstrated. The lipophilic antioxidant coenzyme Q10 (CoQ10) is known as an effective inhibitor of oxidative damage in LDL as well. The aim of the present study was to compare the CoQ10 levels in obese and normal weight children.. The CoQ10 plasma concentrations were measured in 67 obese children (BMI>97th percentile) and related to their degree of insulin resistance. Homeostasis model assessment (HOMA) was used to detect the degree of insulin resistance. The results were compared to a control group of 50 normal weight and apparently healthy children. The results of the CoQ10 levels were related to the plasma cholesterol concentrations.. After adjustment to plasma cholesterol, no significant difference in the CoQ10 levels between obese and normal weight children could be demonstrated. Furthermore, there was no difference between insulin-resistant and non-insulin-resistant obese children.. CoQ10 plasma levels are not reduced in obese children and are not related to insulin resistance.

Topics: Adolescent; Body Weight; Child; Cholesterol; Coenzymes; Female; Humans; Insulin Resistance; Lipoproteins, LDL; Male; Obesity; Oxidative Stress; Reference Values; Ubiquinone

Twelve pairs of healthy sedentary males matched for their body mass index (BMI) with either a low insulin response (LIR; a stage of prediabetes) or a high (HIR; controls) to a standardized glucose infusion test (GIT) were studied in respect to their exercise capacities (W(OBLA), W(SL) and relative W(OBLA):W(OBLA) x W(SL)(-10 x 100), muscle fiber composition (%ST), muscle citrate synthase activity (CS), muscle ubiquinone (MUQ), MUQ over %ST (muscle quality index, MQI), and peripheral insulin sensitivity (PIS) as described with insulin-clamp techniques (SIGITmean). LIR and HIR displayed normal PIS and positive relationships versus exercise capacity. LIR's but not HIR's relative W(OBLA) was related to CS as earlier only documented in endurance athletes but at a lower level than in athletes. This pointed at a poor peripheral oxygen delivery in LIR. LIR's MQI decreased relative to HIR's the higher the muscle CS indicating radical related muscle trauma in LIR as in athletes. LIR representing prediabetes described muscle anomalies, which could represent prestages of the lesions observed in type-2 diabetes. They are claimed to be responsible for insulin-, glucose-, lipid-resistance, and peripheral circulatory resistance.

Topics: Adult; Body Mass Index; Citrate (si)-Synthase; Humans; Insulin Resistance; Male; Motor Activity; Muscles; Oxidation-Reduction; Oxygen Consumption; Prediabetic State; Ubiquinone