13-hydroxy-9-11-octadecadienoic-acid and Insulin-Resistance

Topics: Adipocytes; Cell Differentiation; Humans; Insulin Resistance; Ligands; Linoleic Acids; Linoleic Acids, Conjugated; Macrophage Activation; PPAR gamma; Prostaglandin D2

Oxidative stress plays an essential role in the pathogenesis of type 2 diabetes. Anthocyanin, a natural antioxidant, has been reported to reduce oxidative stress and to attenuate insulin resistance and diabetes in animal models; however, the translation of these observations to humans has not been fully tested.. This study was designed to investigate the effects of purified anthocyanins on dyslipidemia, oxidative status, and insulin sensitivity in patients with type 2 diabetes.. A total of 58 diabetic patients were given 160 mg of anthocyanins twice daily or placebo (n = 29/group) for 24 wk in a randomized, placebo-controlled, double-blind trial. Participants and investigators were masked to treatment allocation.. Anthocyanin supplementation significantly decreased serum LDL cholesterol (by 7.9%; P < 0.05), triglycerides (by 23.0%; P < 0.01), apolipoprotein (apo) B-48 (by 16.5%; P < 0.05), and apo C-III (by 11.0%; P < 0.01) and increased HDL cholesterol (by 19.4%; P < 0.05) compared with placebo after the 24-wk intervention. In addition, patients in the anthocyanin group showed higher total radical-trapping antioxidant parameter and ferric ion reducing antioxidant power values than did patients in the placebo group (both P < 0.05). Serum concentrations of 8-iso-prostaglandin F2α, 13-hydroxyoctadecadienoic acid, and carbonylated proteins in patients in the anthocyanin group were significantly less than in patients in the placebo group (23.4%, 25.8%; P < 0.01 and 20%; P = 0.022, respectively). Furthermore, supplementation with anthocyanin lowered fasting plasma glucose (by 8.5%; P < 0.05) and homeostasis model assessment for insulin resistance index (by 13%; P < 0.05), and elevated serum adiponectin (by 23.4%; P < 0.01) and β-hydroxybutyrate (by 42.4%; P = 0.01) concentrations compared with placebo supplementation.. These findings demonstrate that anthocyanin supplementation exerts beneficial metabolic effects in subjects with type 2 diabetes by improving dyslipidemia, enhancing antioxidant capacity, and preventing insulin resistance. This trial was registered at www.clinicaltrials.gov as NCT02317211.

Topics: 3-Hydroxybutyric Acid; Aged; Anthocyanins; Antioxidants; Apolipoprotein B-48; Apolipoprotein C-III; Blood Glucose; Body Mass Index; Cholesterol, HDL; Cholesterol, LDL; Diabetes Mellitus, Type 2; Dietary Supplements; Dinoprost; Dose-Response Relationship, Drug; Double-Blind Method; Dyslipidemias; Female; Humans; Insulin; Insulin Resistance; Linoleic Acids; Male; Middle Aged; Nutrition Assessment; Oxidative Stress; Triglycerides

Oxidative stress plays a key role in the development of type 2 diabetes. However, it is still unknown what kind of oxidative stress underlies the development of type 2 diabetes. We investigated hydroxyoctadecadienoic acid (HODE) isomers, which have been proposed as a biomarker for evaluating oxidative stress in vivo, during the development of diabetes in Tsumura Suzuki Obese Diabetes (TSOD) mouse, a type 2 diabetes model. It was revealed that glucose tolerance and insulin resistance index HOMA-IR in TSOD mice at 5 weeks of age were approximately normal, namely, the mice were in the prediabetic state, but these levels were significantly exacerbated from 8 weeks of age compared with those in Tsumura Suzuki Non Obesity (TSNO) mice (control). Concomitantly, the plasma levels of free-radical-mediated oxidation products, 9- and 13-(E,E)-HODE and 7β-hydroxycholesterol, in TSOD mice were significantly higher than those in TSNO mice at 8, and 8 and 11 weeks of age, respectively. Interestingly, the plasma levels of 10- and 12-(Z,E)-HODE, which are produced specifically by singlet-oxygen-mediated oxidation, in TSOD mice were higher than those in TSNO mice only at 5 weeks of age, and not at 8, 11, and 13 weeks of age. We demonstrated that singlet-oxygen-mediated oxidation occurred in TSOD mice before development of the diabetic phenotypes, including impaired glucose tolerance and insulin resistance. These results suggest that excessive singlet-oxygen-mediated oxidation plays an important role in the pathogenesis of type 2 diabetes.

Topics: Animals; Biomarkers; Diabetes Mellitus, Type 2; Disease Models, Animal; Free Radicals; Glucose Intolerance; Insulin Resistance; Linoleic Acids; Linoleic Acids, Conjugated; Male; Mice; Mice, Inbred Strains; Mice, Obese; Oxidative Stress; Singlet Oxygen