dinoprost and Insulin-Resistance

We have previously shown that medroxyprogesterone acetate (MPA), either alone or combined with conjugated equine estrogens (CEE), significantly decreased insulin sensitivity (SI), compared with both untreated controls and those treated with CEE alone. The purpose of this study was to determine the effects of estradiol (E2), with and without nomegestrol acetate (NA; a potent progestin that lacks androgenic activity), on SI and arterial antioxidant activity, as determined by F2-isoprostanes. Thirty-six adult female cynomolgus monkeys (Macaca fascicularis) were ovariectomized and fed a moderately atherogenic diet, with one of the following three treatments added to the diet, for 12 weeks: 1) no treatment (control); 2) E2; or 3) continuous combined E2 + NA (E2+NA). SI and glucose effectiveness were assessed by the frequently sampled i.v. glucose tolerance test using a third-phase insulin infusion after 10 weeks of treatment. Cholesterol content and F2-isoprostanes were measured in the thoracic aorta after 12 weeks of treatment. E2 treatment resulted in a significantly greater SI, compared with control or E2+NA-treated monkeys (10.03 +/- 0.91 vs. 6.35 and 6.49 x 10(-4) min(-1) microU(-1) mL; P < 0.05). In contrast to our studies of CEE and MPA, E2+NA treatment, though reducing the SI below that of the E2 group, did not reduce the SI below that of control monkeys. As expected, the short period of treatment resulted in no significant differences in aortic cholesterol content. There was no treatment effect on total F2-isoprostanes (representing F2-isoprostane formation caused primarily by autooxidation), suggesting minimal antioxidant activity. However, there was a treatment difference in the prostaglandin F2alpha (PGF2alpha) isomer (a prostaglandin (PG) isomer formed by both autooxidation of arachidonate and cyclooxygenase activity). PGF2alpha concentrations were 32% lower with E2 treatment, compared with controls, and 36% lower, compared with E2+NA treatment (0.48 +/- 0.08 vs. 0.71 +/- 0.12 and 0.75 +/- 0.06; P < 0.05), suggesting differences in PG synthesis between hormone treatments. In conclusion, NA, a progestin without androgenic activity, may still affect some cardiovascular risk factors differently than estrogen-only therapy. However, it seems to be less detrimental than MPA.

Topics: Administration, Oral; Animals; Aorta, Thoracic; Cardiovascular Diseases; Cholesterol; Dinoprost; Drug Combinations; Estradiol; Female; Insulin Resistance; Macaca fascicularis; Megestrol; Norpregnadienes; Ovariectomy; Risk Factors

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

Black soy peptides have been shown to possess properties that may decrease blood pressure (BP). To examine the effects of black soy peptide supplementation on BP and oxidative stress in subjects with prehypertension or stage I hypertension, 100 participants with an initial untreated systolic blood pressure (SBP) of 130-159 mm Hg, diastolic blood pressure (DBP) of 80-99 mm Hg or both were enrolled. Participants were randomly assigned to either a group ingesting supplement containing 4.5 g black soy peptides daily or a placebo group for 8 weeks. SBP and DBP decreased after 8-week black soy peptide supplementation versus controls (P<0.001). At 8 weeks, SBP decrease was significantly greater for the black soy peptide group (-9.69 ± 12.37 mm Hg) than for the control group (-2.91 ± 13.29 mm Hg) after adjusting for the baseline levels (P = 0.015). Plasma malondialdehyde (MDA) and urinary 8-epi-prostaglandin F2α decreased (P = 0.004 and P = 0.046, respectively) and plasma superoxide dismutase (SOD) activity increased (P<0.001) following 8 weeks of black soy peptide supplementation versus baselines. The MDA decreases (P = 0.022) and SOD activity and nitric oxide (NO) increases (P = 0.022 and P<0.001, respectively) were greater for the black soy peptide group than for the control group. Changes in SBP negatively correlated with changes in NO (r = -0.343, P = 0.001). Changes in angiotensin-converting enzyme activity negatively correlated with NO decreases (r = -0.490, P<0.001) and SOD activity increases (r = -0.338, P = 0.001). Black soy peptide dietary supplementation significantly reduces SBP and oxidative stress in patients with prehypertension and stage I hypertension.

Topics: Adult; Aged; Anthropometry; Blood Glucose; Blood Pressure; C-Reactive Protein; Dietary Supplements; Dinoprost; Double-Blind Method; Eating; Female; Humans; Insulin; Insulin Resistance; Lipids; Male; Malondialdehyde; Middle Aged; Motor Activity; Nitric Oxide; Oxidative Stress; Peptidyl-Dipeptidase A; Renin; Superoxide Dismutase

It is uncertain whether saturated fatty acids (SFAs) impair endothelial function and contribute to arterial stiffening.. We tested the effects of replacing SFAs with monounsaturated fatty acids (MUFAs) or carbohydrates on endothelial function and arterial stiffness.. With the use of a parallel-designed randomized controlled trial in 121 insulin-resistant men and women, we measured vascular function after 1 mo of consumption of a high-SFA (HS) diet and after 24 wk after random assignment to the HS diet or diets that contained <10% SFAs and were high in either MUFAs or carbohydrates. The primary outcome was a change in flow-mediated dilation (FMD), and secondary outcomes were changes in carotid to femoral pulse wave velocity (PWV) and plasma 8-isoprostane F2α-III concentrations.. For 112 participants with data available for analysis on the specified outcomes, no significant differences were shown. FMD with the HS reference diet was 6.7 ± 2.2%, and changes (95% CIs) after 6 mo of intervention were +0.3 (-0.4, 1.1), -0.2 (-0.8, 0.5), and -0.1 (-0.6, 0.7) with HS, high-MUFA (HM), and high-carbohydrate (HC) diets, respectively. After consumption of the HS reference diet, the geometric mean (±SD) PWV was 7.67 ± 1.62 m/s, and mean percentages of changes (95% CIs) were -1.0 (-6.2, 4.3) with the HS diet, 2.7 (-1.4, 6.9) with the HM diet, and -1.0 (-5.5, 3.4) with the HC diet. With the HS reference diet, the geometric mean (±SD) plasma 8-isoprostane F2α-III concentration was 176 ± 85 pmol/L, and mean percentage of changes (95% CIs) were 1 (-12, 14) with the HS diet, 6 (-5, 16) with the HM diet, and 4 (-7, 16) with the HC diet.. The replacement of SFAs with MUFAs or carbohydrates in healthy subjects does not affect vascular function. This trial was registered at Current Controlled Trials (http://www.controlled-trials.com/ISRCTN) as ISRCTN 29111298.

Topics: Adult; Diet; Dietary Carbohydrates; Dietary Fats; Dinoprost; Endothelium, Vascular; Fatty Acids; Fatty Acids, Monounsaturated; Female; Humans; Insulin Resistance; Male; Middle Aged; Pulse; Vascular Diseases; Vascular Stiffness; Vasodilation

To investigate whether (i) angiotensin receptor occupying profiles of angiotensin II receptor blockers (ARBs) vary among the drugs and (ii) such differences contribute to the degree of their pleiotropic effects.. In a randomized, three phase crossover study, nine hypertensive patients received repeated doses (each recommended starting dose for 7 days and then each maximum recommended dose for 20 days) of irbesartan, valsartan and candesartan. The time course profiles and trough level of receptor occupancy were determined on days 7 and 28, respectively. The pleiotropic effect related parameters were measured on days 0 and 28 in each trial.. Of the pleiotropic effect related parameters investigated, urinary 8-isoprostane, fasting serum insulin and homeostasis model assessment of insulin resistance index were more suppressed after 4 weeks treatment with irbesartan than after candesartan and valsartan therapy, respectively. The maximum, area under the curve and trough values of receptor occupancy significantly differed between the ARBs [geometric mean (and 95% CI) of trough value 18.1 (12.9, 25.3) for irbesartan, 9.6 (6.0, 15.3) for valsartan and 5.5 (2.8, 10.8) for candesartan, respectively] and were negatively correlated with the change in urinary 8-isoprostane (r = -0.46 - -0.55, P < 0.05), but not the markers of insulin resistance (r = 0.02-0.15, P = 0.46-0.94).. Our results demonstrate that the receptor occupying profiles are different among the ARBs. This class of drugs might have both receptor occupancy dependent and independent pleiotropic effects.

Topics: Adult; Angiotensin II Type 1 Receptor Blockers; Antihypertensive Agents; Area Under Curve; Benzimidazoles; Biphenyl Compounds; Blood Pressure; Cross-Over Studies; Dinoprost; Double-Blind Method; Enzyme-Linked Immunosorbent Assay; Humans; Hypertension; Insulin; Insulin Resistance; Irbesartan; Luminescent Measurements; Male; Middle Aged; Oxidative Stress; Radioligand Assay; Receptors, Angiotensin; Tetrazoles; Time Factors; Valine; Valsartan; Young Adult

Nitric oxide plays a pivotal role in regulating vascular tone. Different studies show endothelial function is impaired during hyperglycemia. Dark chocolate increases flow-mediated dilation in healthy and hypertensive subjects with and without glucose intolerance; however, the effect of pretreatment with dark chocolate on endothelial function and other vascular responses to hyperglycemia has not been examined. Therefore, we aimed to investigate the effects of flavanol-rich dark chocolate administration on (1) flow-mediated dilation and wave reflections; (2) blood pressure, endothelin-1 and oxidative stress, before and after oral glucose tolerance test (OGTT). Twelve healthy volunteers (5 males, 28.2±2.7 years) randomly received either 100 g/d dark chocolate or flavanol-free white chocolate for 3 days. After 7 days washout period, volunteers were switched to the other treatment. Flow-mediated dilation, stiffness index, reflection index, peak-to-peak time, blood pressure, endothelin-1 and 8-iso-PGF(2α) were evaluated after each treatment phase and OGTT. Compared with white chocolate, dark chocolate ingestion improved flow-mediated dilation (P=0.03), wave reflections, endothelin-1 and 8-iso-PGF(2α) (P<0.05). After white chocolate ingestion, flow-mediated dilation was reduced after OGTT from 7.88±0.68 to 6.07±0.76 (P=0.027), 6.74±0.51 (P=0.046) at 1 and 2 h after the glucose load, respectively. Similarly, after white chocolate but not after dark chocolate, wave reflections, blood pressure, and endothelin-1 and 8-iso-PGF(2α) increased after OGTT. OGTT causes acute, transient impairment of endothelial function and oxidative stress, which is attenuated by flavanol-rich dark chocolate. These results suggest cocoa flavanols may contribute to vascular health by reducing the postprandial impairment of arterial function associated with the pathogenesis of atherosclerosis.

Topics: Acute Disease; Adult; Blood Pressure; Cacao; Dinoprost; Endothelin-1; Endothelium, Vascular; Female; Flavanones; Glucose Tolerance Test; Humans; Hyperglycemia; Insulin Resistance; Insulin-Secreting Cells; Male; Pulse Wave Analysis

We aimed to evaluate whether 4-week of dietary treatment with rice containing resistant starch reduces blood glucose and oxidative stress as well as improves endothelial function.. Patients with impaired fasting glucose (IFG), impaired glucose tolerance (IGT) or newly diagnosed type 2 diabetes (n = 90) were randomly assigned to either a group ingesting rice containing 6.51 g resistant starch daily or a control rice group for 4-weeks. We assessed fasting and postprandial levels of glucose and insulin, oxidative stress markers and endothelial function using reactive hyperemia peripheral arterial tonometry (RH-PAT).. The diet containing rice with resistant starch reduced fasting insulin and insulin resistance, postprandial glucose (P = 0.010) and insulin levels at 30 min, and glucose and insulin areas under the response curve after the standard meal. Rice with resistant starch also decreased urinary 8-epi-PGF(2α) and plasma malondialdehyde (MDA) and increased the RH-PAT index (P < 0.001) and total nitric oxide (NO). Postprandial changes in glucose at 60 and 120 min and areas under the glucose response curve, MDA, RH-PAT, and total NO of the test group differed significantly from those in the control even after adjusting for baseline values. Overall, changes in the RH-PAT index correlated positively with changes in total NO (r = 0.336, P = 0.003) and superoxide dismutase activity (r = 0.381, P = 0.001) and negatively with changes in MDA (r = -0.358, P = 0.002) and 8-epi-PGF(2α).. In patients with IFG, IGT or newly diagnosed type 2 diabetes, 4-weeks of dietary treatment with rice containing resistant starch was associated with improved endothelial function with reduction of postprandial glucose and oxidative stress compared with control.

Topics: Biomarkers; Blood Glucose; Diabetes Mellitus, Type 2; Digestion; Dinoprost; Double-Blind Method; Endothelium, Vascular; Female; Humans; Hydrolysis; Hyperemia; Insulin; Insulin Resistance; Male; Malondialdehyde; Manometry; Middle Aged; Nitric Oxide; Oryza; Oxidative Stress; Plants, Genetically Modified; Postprandial Period; Prediabetic State; Republic of Korea; Starch; Superoxide Dismutase; Time Factors; Treatment Outcome

This study was designed to determine the effect of exenatide on inflammatory and oxidative stress markers in type 2 diabetes mellitus (T2DM) patients who were suboptimally controlled with metformin and/or sulfonylurea.. Twenty-three patients with T2DM with inadequate glucose control were randomly divided into two groups: exenatide group (E group) (12 patients, 5 μg b.d. × 4 weeks followed by 10 μg b.d. × 12 weeks) and placebo group (P group) (11 patients). Glycosylated hemoglobin (HbA1c), the seven-point glucose profile, daily mean glucose, and glycemic excursion were determined. The effects of exenatide on 8-iso-prostaglandin F2α (PGF2α), monocyte chemoattractant protein-1 (MCP-1), and high-sensitivity C-reactive protein (hs-CRP) were investigated.. Exenatide treatment reduced body weight and body mass index (BMI) and improved HbA1c, the seven-point glucose profile, and daily mean glucose compared with placebo (P < 0.05). Limited glycemic excursion was found in the E group compared with the P group (P < 0.05), including a smaller SD and postprandial glucose excursion. In addition, the oxidative stress maker PGF2α was significantly reduced by exenatide treatment (P < 0.05). The inflammatory markers hs-CRP and MCP-1 were also significantly reduced in the E group compared with the P group (P < 0.05). PGF2α was significantly correlated with glycemic excursion (P < 0.05), whereas MCP-1 was significantly correlated with body weight, BMI, glycemic excursion, and HbA1c (P < 0.05 for all).. Exenatide treatment reduced patient body weight and BMI, improved HbA1c and the seven-point glucose profile, reduced daily mean glucose, limited glycemic excursion, and reduced oxidative stress and inflammatory markers in patients of T2DM having inadequate glucose control.

Topics: Aged; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Biomarkers; Blood Glucose; Body Mass Index; Body Weight; C-Reactive Protein; Chemokine CCL2; Diabetes Mellitus, Type 2; Dinoprost; Double-Blind Method; Exenatide; Glycated Hemoglobin; Humans; Hypoglycemic Agents; In Vitro Techniques; Insulin Resistance; Male; Middle Aged; Oxidative Stress; Peptides; Pilot Projects; Venoms

Fatty acids (FA) can impair glucose metabolism to a varying degree depending on time of exposure and also of type of FA. Here we tested for acute effects of marine n-3 FA on insulin sensitivity, insulin secretion, energy metabolism, and oxidative stress. This was a randomized, double-blind, crossover study in 11 subjects with type 2 diabetes mellitus. A 4-hour lipid infusion (Intralipid [Fresenius Kabi, Halden, Norway], total of 384 mL) was compared with a similar lipid infusion partly replaced by Omegaven (Fresenius Kabi) that contributed a median of 0.1 g fish oil per kilogram body weight, amounting to 0.04 g/kg of marine n-3 FA. Insulin sensitivity was assessed by isoglycemic hyperinsulinemic clamps; insulin secretion (measured after the clamps), by C-peptide glucagon tests; and energy metabolism, by indirect calorimetry. Infusion of Omegaven increased the proportion of n-3 FA in plasma nonesterified fatty acids (NEFA) compared with Intralipid alone (20:5n-3: median, 1.5% [interquartile range, 0.6%] vs -0.2% [0.2%], P = .001; 22:6n-3: 0.8% [0.4%] vs -0.7% [0.2%], P = .001). However, glucose utilization was not affected; neither was insulin secretion or total energy production (P = .966, .210, and .423, respectively, for the differences between the lipid clamps). Omegaven tended to lower oxidation of fat (P = .062) compared with Intralipid only, correlating with the rise in individual n-3 NEFA (r = 0.627, P = .039). The effects of clamping on phospholipid FA composition, leptin, adiponectin, or F(2)-isoprostane concentrations were not affected by Omegaven. Enrichment of NEFA with n-3 FA during a 4-hour infusion of Intralipid failed to affect insulin sensitivity, insulin secretion, or markers of oxidative stress in subjects with type 2 diabetes mellitus.

Topics: Adult; Aged; Biomarkers; Body Composition; C-Peptide; Calorimetry, Indirect; Cross-Over Studies; Diabetes Mellitus, Type 2; Diet; Dinoprost; Double-Blind Method; Fat Emulsions, Intravenous; Fatty Acids, Nonesterified; Fatty Acids, Omega-3; Female; Glucagon; Glucose Clamp Technique; Humans; Infusions, Intravenous; Insulin; Insulin Resistance; Isoprostanes; Male; Middle Aged; Oxidative Stress

Cardiovascular disease (CVD) is the leading cause of mortality in patients with end-stage renal disease (ESRD). The cornerstone of high CVD incidence in ESRD patients is endothelial dysfunction which results from inflammation, oxidative stress and insulin resistance. Although various modalities of hemodialysis (HD) have been presumed to exert different effects on oxidative stress and insulin resistance, solid evidence is still lacking.. 40 ESRD patients undergoing HD were prospectively enrolled and divided randomly into two groups. Patients in each group received either F8 HPS (low-flux) (Group A) or FX80 (high-flux) (Group B) as HD dialyzers for 2 consecutive months. Diet pattern and medications were kept as usual in both groups to avoid considerable blood glucose change during study period. Blood samples were taken at the start and end of the study.. A total of 38 patients (18 and 20 for Groups A and B, respectively) completed the study. Within each group, there was no change in adiponectin, plasma 8-iso-prostaglandin F(2)(alpha), high-sensitivity C-reactive protein, blood glucose and insulin after 2 months of treatment except a significant change of HOMA(IR) (p = 0.02) in high-flux group. The significant change of HOMA(IR) between the two groups (p = 0.017) mainly results from the parallel change of insulin between the two groups (p = 0.03).. For patients receiving HD, the high-flux dialyzer with synthetic polysulfone membranes fails to provide a better anti-inflammatory or antioxidative effect than the low-flux dialyzer; however, the high-flux dialyzer does significantly improve insulin resistance in this short-term study. This result implies that the high-flux dialyzer might provide better cardiovascular protection than the low-flux dialyzer. Therefore, the low-flux dialyzer might be considered for patients who only need short-term HD therapy. Regarding patients under long-term maintenance HD therapy, a high-flux dialyzer might be the choice of dialyzer.

Topics: Adiponectin; Aged; Cardiovascular Diseases; Dinoprost; Endothelial Cells; Endothelium, Vascular; Female; Humans; Insulin Resistance; Kidney Failure, Chronic; Male; Membranes, Artificial; Middle Aged; Oxidative Stress; Renal Dialysis

It has been shown that angiotensin-converting enzyme inhibition or angiotensin receptor blockade may improve endothelial dysfunction, an early manifestation of atherosclerosis, in patients with diabetes. Whether this protective effect is mediated through blood pressure-lowering effects or other specific mechanisms such as a reduction in oxidative stress is not clear. We investigated the influence of losartan, compared with atenolol, on endothelial function and oxidative stress in patients with type 2 diabetes and hypertension.. Thirteen patients were included in this randomized, double-blind, crossover study; they received losartan 50 mg twice daily for 4 weeks followed by atenolol 50 mg twice daily or vice versa. Concomitant medication with renin-angiotensin blocking agents or beta-blockers was withdrawn, whereas other medication remained unchanged. At baseline and after each treatment period, flow-mediated dilation of the brachial artery and oxidative stress were measured in serum samples.. Flow-mediated dilation was increased significantly after 4 weeks' treatment with losartan (3.4 +/- 0.44%) compared with atenolol (2.58 +/- 0.42%; P = 0.01). 8-Isoprostanes, a marker of oxidative stress, were significantly reduced in the losartan group compared with baseline (0.039 +/- 0.007 versus 0.067 +/- 0.006 ng/ml; P = 0.01), but did not differ from baseline with atenolol. Glucose, hemoglobin A1c, highly sensitive C-reactive protein, lipids and systolic blood pressure remained unaltered, whereas diastolic blood pressure tended to be lower in the atenolol group.. This study demonstrates that losartan significantly improved endothelial function in type 2 diabetes patients with hypertension compared with atenolol. This must be independent of the blood pressure-lowering effect of losartan and is probably caused by an antioxidative effect of the angiotensin receptor blocker.

Topics: Antihypertensive Agents; Atenolol; Blood Pressure; Brachial Artery; Cross-Over Studies; Diabetes Mellitus, Type 2; Dinoprost; Double-Blind Method; Endothelium, Vascular; Female; Humans; Hypertension; Insulin Resistance; Losartan; Male; Middle Aged; Oxidative Stress; Regional Blood Flow; Research Design; Treatment Outcome; Vasodilation

We recently showed that trans-10,cis-12 (t10,c12) conjugated linoleic acid (CLA) causes insulin resistance in obese men. However, metabolic effects of the c9,t11 CLA isomer are still unknown in obese men. Because c9,t11 CLA is the predominant CLA isomer in foods and is included in dietary weight-loss products, it is important to conduct randomized controlled studies that use c9,t11 CLA preparations.. We investigated the effects of c9,t11 CLA supplementation on insulin sensitivity, body composition, and lipid peroxidation in a group at high risk for cardiovascular disease.. In a randomized, double-blind, placebo-controlled study, 25 abdominally obese men received 3 g c9,t11 CLA/d or placebo (olive oil). Before and after 3 mo of supplementation, we assessed insulin sensitivity (hyperinsulinemic euglycemic clamp), lipid metabolism, body composition, and urinary 8-iso-prostaglandin F(2alpha) (a major F(2)-isoprostane) and 15-keto-dihydro-prostaglandin F(2alpha), markers of in vivo oxidative stress and inflammation, respectively.. All subjects completed the study. Compared with placebo, c9,t11 CLA decreased insulin sensitivity by 15% (P < 0.05) and increased 8-iso-prostaglandin F(2alpha) and 15-keto-dihydro-prostaglandin F(2alpha) excretion by 50% (P < 0.01) and 15% (P < 0.05), respectively. The decreased insulin sensitivity was independent of changes in serum lipids, glycemia, body mass index, and body fat but was abolished after adjustment for changes in 8-iso-prostaglandin F(2alpha) concentrations. There were no differences between groups in body composition.. A CLA preparation containing the purified c9,t11 CLA isomer increased insulin resistance and lipid peroxidation compared with placebo in obese men. Because c9,t11 CLA occurs in commercial supplements as well as in the diet, the present results should be confirmed in larger studies that also include women.

Topics: Administration, Oral; Adult; Aged; Body Composition; Cholesterol; Dinoprost; Double-Blind Method; Glucose; Humans; Insulin Resistance; Linoleic Acids, Conjugated; Lipid Peroxidation; Male; Middle Aged; Obesity; Oxidative Stress; Stereoisomerism

We investigated the effect of glimepiride, a third-generation sulfonylurea hypoglycemic agent, on insulin resistance in elderly patients with type 2 diabetes, in connection with plasma adiponectin and 8-epi-prostagrandin F2alpha (8-epi-PGF2alpha), an oxidative stress marker.. A total of 17 elderly patients with type 2 diabetes received 12 weeks of treatment with glimepiride. Homeostasis assessment model of insulin resistance (HOMA-IR), homeostasis assessment model of beta-cell function, HbA(1c), C-peptide in 24-h pooled urine (urine CPR), and plasma concentrations of 8-epi-PGF2alpha, tumor necrosis factor-alpha (TNF-alpha), plasminogen activator inhibitor type 1, and adiponectin were measured at various times. The metabolic clearance rate of glucose (MCR-g) was also assessed by a hyperinsulinemic-euglycemic clamp.. After 8 weeks of glimepiride treatment, significant reductions were observed in HbA(1c) (from 8.4 +/- 1.9 to 6.9 +/- 1.0%), HOMA-IR (from 2.54 +/- 2.25 to 1.69 +/- 0.95%), and plasma TNF-alpha concentrations (from 4.0 +/- 2.0 to 2.6 +/- 2.5 pg/ml). MCR-g was significantly increased from 3.92 +/- 1.09 to 5.73 +/- 1.47 mg. kg(-1). min(-1). Plasma adiponectin increased from 6.61 +/- 3.06 to 10.2 +/- 7.14 micro g/ml. In control subjects, who maintained conventional treatment, no significant changes were observed in any of these markers.. Glimepiride remarkably improved insulin resistance, suggested by a significant reduction in HOMA-IR, an increase in MCR-g, and a reduction in HbA(1c) without changing extrapancreatic beta-cell function and urine CPR. Increased plasma adiponectin and decreased plasma TNF-alpha may underlie the improvement of insulin resistance with glimepiride.

Topics: Adiponectin; Aged; Diabetes Mellitus, Type 2; Dinoprost; Female; Humans; Hypoglycemic Agents; Insulin Resistance; Intercellular Signaling Peptides and Proteins; Male; Middle Aged; Osmolar Concentration; Plasminogen Activator Inhibitor 1; Proteins; Sulfonylurea Compounds; Tumor Necrosis Factor-alpha

This study aims to investigate the correlation between oxidative stress and intra-abdominal fat (IAF) in obese young and middle-aged males.The present study included 136 male examinees in the Examination Center of the First Hospital of Qinhuangdao from October 10, 2015 to December 10, 2015. Then, clinical data, oxidative stress indices (8-iso-prostaglandin F2α [8-iso-PGF2α], malondialdehyde [MDA], and superoxide dismutase [SOD]), and IAF area were recorded. All subjects were assigned into 3 groups according to body mass index (BMI): obese group (BMI ≥ 28 kg/m, 43 subjects), overweight group (24 ≤ BMI < 28 kg/m, 46 subjects), and control group (BMI < 24 kg/m, 47 subjects). Then, statistical analysis was performed.There were significant differences in IAF area, leptin, adiponectin, 8-iso-PGF2α, MDA, SOD, fasting insulin (FINS), fasting blood glucose (FBG), and homeostasis model assessment-insulin resistance (HOMA-IR) among these 3 groups (P < .05). Male subjects in the obese group had higher leptin, 8-iso-PGF2α, MDA, FINS, and HOMA-IR levels, compared to subjects in the overweight and control groups. Furthermore, subjects in the overweight group had a larger IAF area and higher 8-iso-PGF2α, MDA, and FBG levels, when compared to controls. In addition, SOD was significantly lower in the obese and overweight groups than in the control group. However, there were no statistical differences in age, systolic and diastolic blood pressure, lipids, and islet β-cell secretion function (homeostasis model assessment-β) among these 3 groups (P ≥ .05). Moreover, the IAF area was positively correlated to 8-iso-PGF2α and MDA, and negatively correlated to SOD.Oxidative stress is significantly associated with the IAF area in obese males, and abdominal obesity could increase oxidative stress level and insulin resistance.

Topics: Adiponectin; Adult; Blood Glucose; Body Mass Index; Dinoprost; Humans; Insulin Resistance; Intra-Abdominal Fat; Leptin; Male; Malondialdehyde; Middle Aged; Obesity; Oxidative Stress; Superoxide Dismutase; Young Adult

A potential contribution of H. pylori contamination to low-grade inflammation, oxidative stress (OS) and insulin resistance as well as correlations between these parameters in asymptomatic sedentary males was analysed. We enrolled 30 apparently healthy asymptomatic young subjects (18 H. pylori negative and 12 positive) and measured whole blood glucose, glycated haemoglobin, insulin, C-peptide, cortisol, aldosterone, testosterone, thyroid stimulating hormone, C-reactive protein, interleukins 6 and 10, TNF-alpha and comet assay. As markers of OS, we used urine levels of iso-PGF

Topics: Adult; Asymptomatic Diseases; Biomarkers; Dinoprost; Helicobacter pylori; Humans; Inflammation; Insulin Resistance; Male; Sedentary Behavior; Young Adult

In this prospective study, we evaluated the association of retinoic acid (RA) with the metabolic syndrome (MetS) in the Chinese population.. A total of 1042 nondiabetic adults from the population-based Nutrition and Health of Aging Population were prospectively followed up for 4 years. Serum RA concentrations was determined and its relationship with the MetS and its component was investigated.. At baseline, higher RA levels were inversely associated with the presence of MetS (odds ratio 0.61; 95% confidence interval [CI] 0.44–0.74, P < .001) after adjustment for age, gender, body mass index, the homeostasis model assessment index for insulin resistance (HOMA-IR), and other confounding factors. Subjects with lower RA levels had a progressively worse cardiometabolic risk profile at baseline. Serum RA levels were inversely associated with 8-iso-prostaglandin F2α (P < .001), high-sensitivity C-reactive protein (P = .015), and IL-6 (P = .020) and positively correlated with high-density lipoprotein cholesterol (P = .038). Among 825 subjects without MetS at baseline, 146 had developed it at 4 years. Serum RA by quartiles was inversely correlated with the incident MetS (adjusted hazard ratio 0.67; 95% CI 0.48–0.81, P = .006). Apart from HOMA-IR (P < .001), the baseline RA level was the only independent predictor of the development of the MetS during the 4-year follow-up (odds ratio 0.53; 95% CI 0.40–0.69; P < .001) after adjustment for age, gender, body mass index, and HOMA-IR.. The serum RA level is inversely associated with the development of MetS independently of adiposity and insulin resistance.

Topics: Adiposity; Age Factors; Aged; Body Mass Index; C-Reactive Protein; Cholesterol, HDL; Dinoprost; Female; Follow-Up Studies; Health Surveys; Humans; Insulin Resistance; Male; Metabolic Syndrome; Middle Aged; Prospective Studies; Sex Factors; Tretinoin

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

Adults with metabolic syndrome from different race/ethnicities are often predisposed to developing type 2 diabetes (T2D); however, growing evidence suggests that healthy diets and lifestyle choices can significantly slow or prevent progression to T2D. This poorly understood relationship to healthy dietary patterns and prevention of T2D motivated us to conduct a retrospective analysis to determine the potential impact of a minor dietary lifestyle change (daily mushroom consumption) on known T2D risk factors in racially diverse adults with confirmed features of the metabolic syndrome. Retrospectively, we studied 37 subjects who had participated in a dietary intervention focused on vitamin D bioavailability from white button mushrooms (WBM). All 37 had previously completed a 16-week study where they consumed 100 g of WBM daily and were then followed-up for one month during which no mushrooms were consumed. We analyzed differences in serum risk factors from baseline to 16-week, and from baseline to one-month follow-up. Measurement of serum diabetic risk factors included inflammatory and oxidative stress markers and the antioxidant component naturally rich in mushrooms, ergothioneine. Significant beneficial health effects were observed at 16-week with the doubling of ergothioneine from baseline, increases in the antioxidant marker ORAC (oxygen radical absorption capacity) and anti-inflammatory hormone, adiponectin and significant decreases in serum oxidative stress inducing factors, carboxymethyllysine (CML) and methylglyoxal (MG), but no change in the lipid oxidative stress marker 8-isoprostane, leptin or measures of insulin resistance or glucose metabolism. We conclude that WBM contain a variety of compounds with potential anti-inflammatory and antioxidant health benefits that can occur with frequent consumption over time in adults predisposed to T2D. Well-controlled studies are needed to confirm these findings and identify the specific mushroom components beneficial to health.

Topics: Adiponectin; Adult; Agaricus; Antioxidants; beta-Glucans; Biomarkers; Body Mass Index; Chitin; Cholesterol, HDL; Cholesterol, LDL; Diabetes Mellitus, Type 2; Diet; Dinoprost; Ergothioneine; Female; Follow-Up Studies; Glycated Hemoglobin; Humans; Insulin Resistance; Leptin; Linear Models; Lysine; Male; Metabolic Syndrome; Middle Aged; Multivariate Analysis; Oxidative Stress; Polyphenols; Pyruvaldehyde; Retrospective Studies; Risk Factors; Triglycerides; Vitamin D

Oxidative stress has been implicated in the pathogenesis of many conditions, including insulin resistance and obesity. However, in vivo data concerning these relationships are scarce and conflicting. Therefore, the aim of this study was to investigate the association of oxidative stress with abdominal adiposity and insulin resistance in individuals at high cardiometabolic risk.. A total of 116 overweight/obese individuals participating in the HealthGrain and Etherpaths European Projects, having waist circumference (WC) and any other component of the metabolic syndrome, were included in this cross-sectional evaluation. 8-Isoprostane concentrations in 24-hr urine were measured as marker of oxidative stress in vivo. Baseline anthropometric and metabolic parameters were analyzed according to quartiles of 8-isoprostanes. Linear regression (LR) analysis was used to assess clinical correlates of oxidative stress.. Urinary 8-isoprostane levels were 52% higher in men than in women (P<0.001). Across the isoprostanes quartiles, there was a significant increase in WC and body weight [P for trend<0.001; analysis of variance (ANOVA) P<0.001] and fasting triglycerides (P for trend<0.05; ANOVA P<0.05), and a significant decrease in high-density lipoprotein cholesterol (P for trend<0.001; ANOVA P=0.001). No significant association between urinary isoprostane concentrations and insulin resistance [homeostasis model assessment of insulin resistance (HOMA-IR)] was found. WC circumference and body weight remained significant after adjustment for age and gender (P=0.023 and P=0.014, respectively) and independently associated with isoprostanes at LR (P<0.005 for both).. Central obesity was independently associated with oxidative stress even in a population homogeneous for adiposity and cardiometabolic risk, whereas no relationship was observed between oxidative stress and insulin resistance.

Topics: Abdominal Fat; Adiposity; Adult; Age Factors; Aged; Body Weight; Cholesterol, HDL; Cross-Sectional Studies; Dinoprost; Female; Humans; Insulin Resistance; Male; Metabolic Syndrome; Middle Aged; Obesity; Overweight; Oxidative Stress; Risk Assessment; Sex Characteristics; Triglycerides; Waist Circumference

Since epidemiologic studies suggest that tobacco smoke toxins, e.g. the nicotine-derived nitrosamine ketone (NNK) tobacco-specific nitrosamine, can be a co-factor in alcohol-related brain disease (ARBD), we examined the independent and additive effects of alcohol and NNK exposures on spatial learning/memory, and brain insulin/IGF signaling, neuronal function and oxidative stress.. Adolescent Long Evans rats were fed liquid diets containing 0 or 26% caloric ethanol for 8 weeks. During weeks 3-8, rats were treated with i.p. NNK (2 mg/kg, 3×/week) or saline. In weeks 7-8, ethanol groups were binge-administered ethanol (2 g/kg; 3×/week). In week 8, at 12 weeks of age, rats were subjected to Morris Water Maze tests. Temporal lobes were used to assess molecular indices of insulin/IGF resistance, oxidative stress and neuronal function.. Ethanol and NNK impaired spatial learning, and NNK ± ethanol impaired memory. Linear trend analysis demonstrated worsening performance from control to ethanol, to NNK, and then ethanol + NNK. Ethanol ± NNK, caused brain atrophy, inhibited insulin signaling through the insulin receptor and Akt, activated GSK-3β, increased protein carbonyl and 3-nitrotyrosine, and reduced acetylcholinesterase. NNK increased NTyr. Ethanol + NNK had synergistic stimulatory effects on 8-iso-PGF-2α, inhibitory effects on p-p70S6K, tau and p-tau and trend effects on insulin-like growth factor type 1 (IGF-1) receptor expression and phosphorylation.. Ethanol, NNK and combined ethanol + NNK exposures that begin in adolescence impair spatial learning and memory in young adults. The ethanol and/or NNK exposures differentially impair insulin/IGF signaling through neuronal growth, survival and plasticity pathways, increase cellular injury and oxidative stress and reduce expression of critical proteins needed for neuronal function.

Topics: Acetylcholinesterase; Animals; Atrophy; Dinoprost; Drug Synergism; Ethanol; Glycogen Synthase Kinase 3; Glycogen Synthase Kinase 3 beta; Insulin; Insulin Resistance; Male; Maze Learning; Nicotine; Nitrosamines; Oxidative Stress; Phosphorylation; Protein Carbonylation; Rats; Receptor, IGF Type 1; Ribosomal Protein S6 Kinases, 70-kDa; Signal Transduction; Somatomedins; Spatial Learning; tau Proteins; Temporal Lobe; Tyrosine

Piperidine-based peroxisome proliferator-activated receptor-α agonists are agents that are efficacious in improving lipid, glycemic, and inflammatory indicators in diabetes and obesity. This study sought to determine whether CP-900691 ((S)-3-[3-(1-carboxy-1-methyl-ethoxy)-phenyl]-piperidine-1-carboxylic acid 4-trifluoromethyl-benzyl ester; CP), a member of this novel class of agents, by decreasing plasma triglycerides, could prevent diabetic nephropathy in the Black and Tan, BRachyuric (BTBR) ob/ob mouse model of type 2 diabetes mellitus. Four-week old female BTBR WT and BTBR ob/ob mice received either regular chow or one containing CP (3 mg/kg per day) for 14 weeks. CP elevated plasma high-density lipoprotein, albuminuria, and urinary excretion of 8-epi PGF(2α), a product of the nonenzymatic metabolism of arachidonic acid and whose production is elevated in oxidative stress, in BTBR WT mice. In BTBR ob/ob mice, CP reduced plasma triglycerides and non-esterified fatty acids, fasting blood glucose, body weight, and plasma interleukin-6, while concomitantly improving insulin resistance. Despite these beneficial metabolic effects, CP had no effect on elevated plasma insulin, 8-epi PGF(2α) excretion, and albuminuria, and surprisingly, did not ameliorate the development of diabetic nephropathy, having no effect on the accumulation of renal macrophages, glomerular hypertrophy, and increased mesangial matrix expansion. In addition, CP did not increase plasma high-density lipoprotein in BTBR ob/ob mice, while paradoxically increasing total cholesterol levels. These findings indicate that 8-epi PGF(2α), possibly along with hyperinsulinemia and inflammatory and dysfunctional lipoproteins, is integral to the development of diabetic nephropathy and should be considered as a potential target of therapy in the treatment of diabetic nephropathy.

Topics: Albuminuria; Animals; Anti-Obesity Agents; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Dinoprost; Disease Progression; Female; Glomerular Mesangium; Hypercholesterolemia; Hypertriglyceridemia; Hypertrophy; Hypoglycemic Agents; Hypolipidemic Agents; Insulin Resistance; Kidney; Mice; Mice, Inbred Strains; Mice, Obese; Obesity; Piperidines; PPAR alpha; Propionates

Because alterations in blood fatty acid (FA) composition by dietary lipids are associated with insulin resistance and related metabolic disorders, we hypothesized that serum phospholipid FA composition would reflect the early alteration of fasting glycemic status, even in people without metabolic syndrome (MetS). To examine this hypothesis, serum phospholipid FA, desaturase activities, fasting glycemic status, and cardiometabolic parameters were measured in study participants (n = 1022; 30-69 years; male, n = 527; female, n = 495; nondiabetics without disease) who were stratified into normal fasting glucose (NFG) and impaired fasting glucose (IFG) groups. Total monounsaturated FA (MUFA), oleic acid (OA; 18:1n-9), dihomo-γ-linolenic acid (DGLA; 20:3n-6), Δ-9-desaturase activity (D9D; 18:1n-9/18:0), and DGLA/linoleic acid (20:3n-6/18:2n-6) in serum phospholipids were significantly higher in IFG subjects than NFG controls. Study subjects were subdivided into 4 groups, based on fasting glucose levels and MetS status. Palmitoleic acid (16:1n-7) was highest in IFG-MetS and lowest in NFG-non-MetS subjects. Oleic acid and D9D were higher in IFG-MetS than in the other 3 groups. Dihomo-γ-linolenic acid and DGLA/linoleic acid were higher in MetS than in non-MetS, regardless of fasting glucose levels. The high-sensitivity C-reactive proteins (hs-CRPs) and 8-epi-prostaglandin-F2α were higher in IFG than in NFG, regardless of MetS status. Oxidized low-density lipoproteins were higher in IFG-MetS than in the other 3 groups. Total MUFAs, OA, and D9D were positively correlated with homeostasis model assessment of insulin resistance, fasting glucose, triglyceride, hs-CRP, and 8-epi-prostaglandin-F2α. Palmitoleic acid was positively correlated with triglyceride and hs-CRP. Lastly, total MUFA, OA, palmitoleic acid, and D9D were associated with early alteration of fasting glycemic status, therefore suggesting that these may be useful markers for predicting the risk of type 2 diabetes and cardiometabolic diseases.

Topics: 8,11,14-Eicosatrienoic Acid; Biomarkers; Blood Glucose; C-Reactive Protein; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Dinoprost; Fasting; Fatty Acids, Monounsaturated; Female; Humans; Insulin; Insulin Resistance; Linoleic Acid; Lipoproteins, LDL; Male; Metabolic Syndrome; Middle Aged; Oleic Acid; Phospholipids; Stearoyl-CoA Desaturase; Triglycerides

The aim of the present study was to assess oxidative stress and iron metabolism in systemic lupus erythematosus (SLE) patients with and without insulin resistance (IR).. This study included 236 subjects (125 controls and 111 SLE patients). Patients with SLE were divided in two groups: with (n = 72) or without (n = 39) IR.. SLE patients with IR showed higher advanced oxidation protein product (AOPP) levels (p = 0.030) and gamma-glutamyltransferase (GGT) levels (p = 0.001) and lower sulfhydryl groups of proteins (p = 0.0002) and total radical-trapping antioxidant parameter (TRAP) corrected by uric acid (UA) levels (p = 0.04) when compared to SLE patients without IR. However, SLE patients with IR presented lower serum 8-isoprostane (p = 0.05) and carbonyl protein levels (p = 0.04) when compared to SLE patients without IR. Serum ferritin levels were significantly higher in SLE patients (p = 0.0006) than in controls, and SLE patients with IR presented higher serum ferritin levels (p = 0.01) than SLE patients without IR. Patients with SLE showed that IR was inversely correlated to TRAP/UA (r = -0.2724, p = 0.0008) and serum ferritin was positively correlated to AOPP (r = 0.2870, p = 0.004).. This study found that oxidative stress was higher in the group of SLE patients with IR, and increased ferritin, whether caused by the inflammatory process per se or hyperinsulinaemia, can favour the redox process. In addition, the preset data reinforce the need to measure oxidative stress with several methodologies with different assumptions.

Topics: Adult; Age Factors; Anthropometry; Biomarkers; Case-Control Studies; Dinoprost; Disease Progression; Female; Ferritins; Follow-Up Studies; gamma-Glutamyltransferase; Humans; Insulin Resistance; Lupus Erythematosus, Systemic; Male; Middle Aged; Oxidative Stress; Sex Factors; Statistics, Nonparametric

Although many obese individuals are normoglycemic and asymptomatic of cardiometabolic complications, this apparent healthy state may be a misnomer. Since heart failure is a major cause of mortality in obesity, we investigated the effects of heme-oxygenase (HO) on heart failure and cardiometabolic complications in obese normoglycemic Zucker-fatty rats (ZFs). Treatment with the HO-inducer, hemin, reduced markers of heart failure, such as osteopontin and osteoprotegerin, abated left-ventricular (LV) hypertrophy/fibrosis, extracellular matrix/profibrotic proteins including collagen IV, fibronectin, TGF-β1, and reduced cardiac lesions. Furthermore, hemin suppressed inflammation by abating macrophage chemoattractant protein-1, macrophage-inflammatory protein-1 alpha, TNF-α, IL-6, and IL-1β but enhanced adiponectin, atrial-natriuretic peptide (ANP), HO activity, insulin sensitivity, and glucose metabolism. Correspondingly, hemin improved several hemodynamic/echocardiographic parameters including LV-diastolic wall thickness, LV-systolic wall thickness, mean-arterial pressure, arterial-systolic pressure, arterial-diastolic pressure, LV-developed pressure, +dP/dt, and cardiac output. Contrarily, the HO-inhibitor, stannous mesoporphyrin nullified the hemin effect, exacerbating inflammatory/oxidative insults and aggravated insulin resistance (HOMA-index). We conclude that perturbations in insulin signaling and cardiac function may be forerunners to overt hyperglycemia and heart failure in obesity. Importantly, hemin improves cardiac function by suppressing markers of heart failure, LV hypertrophy, cardiac lesions, extracellular matrix/profibrotic proteins, and inflammatory/oxidative mediators, while concomitantly enhancing the HO-adiponectin-ANP axis.

Topics: Adiponectin; Animals; Atrial Natriuretic Factor; Blood Glucose; Chemokine CCL2; Dinoprost; Endothelin-1; Heart Failure; Heart Function Tests; Heart Ventricles; Heme Oxygenase (Decyclizing); Hemin; Hemodynamics; Inflammation; Insulin; Insulin Resistance; Macrophage Inflammatory Proteins; Macrophages; Metalloporphyrins; Myocytes, Cardiac; Obesity; Rats; Rats, Zucker; Risk Factors; Tumor Necrosis Factor-alpha; Ultrasonography; Up-Regulation

Oxidative stress is associated with obesity, metabolic syndrome and inflammation, suggesting it could be an early event in the pathology of chronic diseases. We tested the hypothesis that elevated levels of oxidative stress markers are associated with increased C-reactive protein (CRP) and that this is independent of obesity and insulin resistance.. This study was cross-sectional designed and nondiabetic postmenopausal women (n = 1821) with CRP levels ≤10 mg/l was enrolled. The CRP levels were categorized into quartiles from the lowest to the highest concentrations (Q1-Q4). The degree of insulin resistance was determined using the homoeostasis model assessment of insulin resistance (HOMA-IR). We measured oxidative stress using urinary 8-epi-prostaglandin F2α (8-epi-PGF2α) and plasma oxidized low-density lipoprotein (ox-LDL).. After adjustments for age and lifestyle habits, including smoking and drinking, we found higher body mass index (BMI) and HOMA-IR scores in Q2 and Q3 vs Q1. The Q4 BMI and HOMA-IR scores were higher than all other quartiles. The plasma ox-LDL was higher in Q4 than in Q1. Urinary 8-epi-PGF2α was higher in Q3 and Q4 than in Q1 or Q2. Urinary 8-epi-PGF2α positively correlated with CRP (r = 0·235, P < 0·001), whereas no correlation was found between ox-LDL and CRP. Multiple linear regression analyses of BMI and HOMA-IR showed that the association between urinary 8-epi-PGF2α and CRP levels remained significant (P < 0·001).. Oxidative stress measured by increased concentration of urine 8-epi-PGF2α is strongly associated with CRP levels. This finding was independent of obesity and insulin resistance in nondiabetic postmenopausal women.

Topics: Aged; Blood Glucose; Body Mass Index; C-Reactive Protein; Dinoprost; Female; Homeostasis; Humans; Insulin; Insulin Resistance; Linear Models; Lipoproteins, LDL; Middle Aged; Obesity; Oxidative Stress; Postmenopause; Risk Factors

Secreted frizzled-related protein 5 (Sfrp5) has been described as novel adipokine in mice with insulin-sensitising and anti-inflammatory properties similar to adiponectin. The aim of this study was to compare serum concentrations and determinants of Sfrp5, its pro-inflammatory antagonist wingless-type MMTV integration site family member (Wnt)5a and adiponectin in humans and their regulation by coffee.. Serum concentrations of Sfrp5, Wnt5a and adiponectin were measured in 47 individuals who participated in a coffee intervention study. Associations with demographic, metabolic and immunological variables and regulation of serum levels by different amounts of daily coffee intake were analysed.. At baseline, fasting serum Sfrp5 levels ranged between 96 and 4056 ng/mL. Sfrp5 was directly correlated with a surrogate of insulin resistance (homeostasis model assessment of insulin resistance/HOMA-IR; r = 0·32, P < 0·05) and with the oxidative stress markers 8-isoprostane (r = 0·44, P < 0·01) and nitrotyrosine (r = 0·52, P < 0·001). Adiponectin showed inverse correlations with several indices of insulin resistance (e.g. HOMA-IR, Stumvoll index; all P < 0·05) and a direct correlation with the anti-atherogenic apolipoprotein A-I (r = 0·56, P < 0·001). Coffee did not affect serum concentrations of Sfrp5. Serum Wnt5a concentrations were below the detection limit (0·02 ng/mL) in 81% of the study participants.. In contrast to obese mouse models, serum Sfrp5 was directly related to HOMA-IR and oxidative stress in humans, but not with apolipoproteins, and thus, associations differed from those found for circulating adiponectin. These differences between Sfrp5 and adiponectin might be explained by differences in the investigated species.

Topics: Adaptor Proteins, Signal Transducing; Adiponectin; Animals; Body Mass Index; Clinical Trials as Topic; Coffee; Dinoprost; Eye Proteins; Humans; Insulin; Insulin Resistance; Membrane Proteins; Mice; Middle Aged; Models, Animal; Obesity; Oxidative Stress; Proto-Oncogene Proteins; Statistics as Topic; Tyrosine; Wnt Proteins; Wnt Signaling Pathway; Wnt-5a Protein

The assessment of oxidative stress may aid in the identification of subsequent metabolic risk in obese children. The objective of this study was to determine whether the plasma level of advanced oxidation protein products, analyzed with a recently proposed modified assay that involves a delipidation step (mAOPPs), was related to metabolic risk factors (MRFs) in severely obese children.. The plasma levels of mAOPPs were determined by spectrophotometry in 54 severely obese and 44 healthy children. We also measured lipid peroxidation biomarkers (thiobarbituric acid-reactive substances, malondialdehyde, and 8-isoprotane F(2α)) and sulfhydryl groups, a marker of antioxidant defense. Protein oxidation and lipid peroxidation markers were higher and sulfhydryl levels were lower in obese children compared with controls. Taking metabolic risk into account, obese children were subdivided according to the cutoff point (53.2 μmol/L) obtained for their mAOPPs values from the ROC curve. Anthropometric measures and the existence of hypertension did not differ between groups. The presence of dyslipidemia and insulin resistance was significantly higher in the group with higher mAOPPs levels. The highest levels of mAOPPs were found in the children with ≥3 MRFs. The level of mAOPPs was positively correlated with triglycerides and negatively correlated with high-density lipoprotein cholesterol. There was no correlation of this marker of protein oxidation with biomarkers of lipid peroxidation.. The determination of mAOPPs in delipidated plasma is an easy way to evaluate protein oxidation. It may be useful in severely obese children for better cardiovascular risk assessment.

Topics: Adolescent; Age of Onset; Biomarkers; Chi-Square Distribution; Child; Dinoprost; Dyslipidemias; Female; Humans; Hypertension; Insulin Resistance; Linear Models; Lipid Peroxidation; Lipids; Male; Malondialdehyde; Metabolic Syndrome; Obesity; Oxidation-Reduction; Oxidative Stress; Proteins; Risk Assessment; Risk Factors; Severity of Illness Index; Spain; Spectrophotometry; Sulfhydryl Compounds; Thiobarbituric Acid Reactive Substances; Up-Regulation

Epidemiological evidence suggests that whole grain intake is associated with reduced risk of type 2 diabetes. However, studies of individual whole grains on the prevention of type 2 diabetes are lacking. The objective of the present study was to examine the effect of different whole grains on type 2 diabetes in an animal model of type 2 diabetes, the Goto-Kakisaki (GK) rat. GK rats were fed either a basal diet or a whole grain-containing diet for 5 months. Whole grain diets contained 65 % whole grain flours of wheat, barley, oats or maize. After 2 months of feeding, fasting plasma glucose concentrations were lower in the wheat, barley and oats groups, compared with the basal group, whereas glycated Hb was significantly greater in the wheat group compared with other groups. Feeding of whole barley and maize increased plasma C-peptide concentrations compared with whole wheat at 2 months. There was a trend in the improvement of insulin resistance with a consumption of barley and oats diets at 2 months (P = 0·06) compared with the basal diet. Oxidative stress markers, urinary thiobarbituric acid-reactive substances and 8-isoprostane, did not improve with whole grain intake at 2 months. At 5 months, whole grain diets did not differ from the basal diet in glycaemic control, insulin secretion, oxidative stress and preservation of pancreatic β-cell mass. These results suggest that the consumption of whole grains may offer modest benefit early in the development of type 2 diabetes, but this benefit is lost with further development of the disease.

Topics: Animals; Antioxidants; Biomarkers; C-Peptide; Diabetes Mellitus, Type 2; Dietary Fiber; Dinoprost; Disease Progression; Edible Grain; Food Handling; Functional Food; Glycated Hemoglobin; Hyperglycemia; Insulin Resistance; Insulin-Secreting Cells; Male; Oxidative Stress; Random Allocation; Rats; Rats, Mutant Strains; Rats, Wistar; Thiobarbituric Acid Reactive Substances

Although a relationship between obesity and hyperthyrotropinemia has been hypothesized in obese children, the underlying pathogenesis is not completely known. In the current cross-sectional study, we evaluated the thyroid function in a group of 80 obese pre-pubertal children compared to 41 healthy normal weight peers, exploring the possible association between hyperthyrotropinemia and oxidative stress. In all children, thyrotropin (TSH), free T4 (fT4), free T3 (fT3) and anti-thyroid antibodies were evaluated. Homeostatic model assessment of insulin resistance (HOMA-IR) level was evaluated as index of insulin resistance. We measured the endogenous secretory receptor for advanced glycation end products (esRAGE) and soluble RAGE (sRAGE) and the urinary prostaglandin F2α (PGF-2α) as markers of oxidative stress. We found that TSH levels were significantly higher in obese children than controls. TSH significantly correlated with body mass index-standard deviation score (BMI-SDS), HOMA-IR, PGF-2α, esRAGE and sRAGE. The multiple linear regression showed that in obese children HOMA-IR, PGF-2α, esRAGE and sRAGE were significantly related to TSH, independently of BMI-SDS, age and gender. In obese children, hyperthyrotropinemia could be detected already in pre-pubertal age. The increased oxidative stress might represent one of the key regulators of TSH levels, early in life.

Topics: Age Factors; Autoantibodies; Blood Glucose; Body Mass Index; Child; Cross-Sectional Studies; Dinoprost; Female; Humans; Insulin Resistance; Lipids; Male; Obesity; Oxidative Stress; Puberty; Receptor for Advanced Glycation End Products; Receptors, Immunologic; Sex Factors; Thyroid Gland; Thyroid Hormones; Thyrotropin; Ultrasonography

Negative regulators of white adipose tissue (WAT) expansion are poorly documented in vivo. Prostaglandin F(2α) (PGF(2α)) is a potent antiadipogenic factor in cultured preadipocytes, but evidence for its involvement in physiological context is lacking. We previously reported that Akr1b7, an aldo-keto reductase enriched in adipose stromal vascular fraction but absent from mature adipocytes, has antiadipogenic properties possibly supported by PGF(2α) synthase activity. To test whether lack of Akr1b7 could influence WAT homeostasis in vivo, we generated Akr1b7(-/-) mice in 129/Sv background. Akr1b7(-/-) mice displayed excessive basal adiposity resulting from adipocyte hyperplasia/hypertrophy and exhibited greater sensitivity to diet-induced obesity. Following adipose enlargement and irrespective of the diet, they developed liver steatosis and progressive insulin resistance. Akr1b7 loss was associated with decreased PGF(2α) WAT contents. Cloprostenol (PGF(2α) agonist) administration to Akr1b7(-/-) mice normalized WAT expansion by affecting both de novo adipocyte differentiation and size. Treatment of 3T3-L1 adipocytes and Akr1b7(-/-) mice with cloprostenol suggested that decreased adipocyte size resulted from inhibition of lipogenic gene expression. Hence, Akr1b7 is a major regulator of WAT development through at least two PGF(2α)-dependent mechanisms: inhibition of adipogenesis and lipogenesis. These findings provide molecular rationale to explore the status of aldo-keto reductases in dysregulations of adipose tissue homeostasis.

Topics: 3T3-L1 Cells; Adipogenesis; Adipose Tissue, White; Adiposity; Aldehyde Reductase; Animals; Anti-Obesity Agents; Cell Size; Cloprostenol; Crosses, Genetic; Diet, High-Fat; Dinoprost; Disease Susceptibility; Down-Regulation; Insulin Resistance; Lipogenesis; Mice; Mice, 129 Strain; Mice, Inbred C57BL; Mice, Knockout; Molecular Targeted Therapy; Obesity

Most deaths in autosomal dominant polycystic kidney disease (ADPKD) are attributable to cardiovascular disease (CVD). We examined novel CVD biomarkers in different stages of ADPKD.. We recruited 50 hypertensive subjects with ADPKD with estimated GFR (eGFR) of >60 ml/min per 1.73 m(2); 52 hypertensive subjects with ADPKD with eGFR of 25 to 60 ml/min per 1.73 m(2); 42 normotensive subjects with ADPKD and eGFR of >60 ml/min per 1.73 m(2); and 50 healthy controls. We assayed serum C-reactive protein and IL-6 as markers of inflammation; plasma 8-epi-prostaglandin F(2α (8-epi-PGF2α)) and superoxide dismutase (SOD) as markers of oxidative stress; and homeostasis model assessment (HOMA) as a measure of insulin resistance.. The hypertensive ADPKD eGFR of 25 to 60 group had higher levels of C-reactive protein and IL-6 than controls, normotensive ADPKD with eGFR of >60, and hypertensive ADPKD with eGFR of >60. The normotensive ADPKD eGFR >60, hypertensive ADPKD eGFR >60, and hypertensive ADPKD eGFR 25 to 60 groups had higher 8-epi-PGF(2α) and lower SOD than controls, with no difference between the ADPKD groups. There was no difference in HOMA levels between any of the groups. Adjustment for age, race, gender, and body mass index did not alter these relationships.. Inflammation and oxidative stress are evident early in ADPKD even with preserved kidney function. Inflammation exhibits a graded relationship with levels of kidney function, whereas oxidative stress demonstrates a threshold effect. These pathways may be therapeutic targets for CVD risk mitigation.

Topics: Adult; C-Reactive Protein; Dinoprost; Female; Glomerular Filtration Rate; Humans; Hypertension; Inflammation; Insulin Resistance; Interleukin-6; Male; Middle Aged; Oxidative Stress; Polycystic Kidney, Autosomal Dominant; Superoxide Dismutase

Type 2 diabetes is a heterogeneous metabolic disease characterized by insulin resistance and β-cell dysfunction leading to hyperglycaemia and dyslipidaemia. Dietary intervention seems to improve some of these cellular complications, namely insulin resistance. Our aim was to evaluate the effects of dietary restriction on systemic and skeletal muscle oxidative stress and insulin resistance in normal Wistar rats and Goto-Kakizaki (GK) rats, a non-obese type 2 diabetic animal model. Four-month-old normal and diabetic rats were separated in four groups. One group of each strain was maintained with ad libitum standard diet, and the other group was submitted to a dietary restriction (50% of control animals daily food intake), during 2 months. Metabolic profile, insulin resistance indexes and muscle lipids were determined. Oxidative stress parameters were also measured at systemic and muscle levels: protein carbonyl, 8-hydroxy-2'-deoxyguanosine and free 8-isoprostane. Dietary restriction improved lipid profile in both strains and urinary free 8-isoprostane and plasma carbonyl compounds in diabetic rats. An improvement of muscle triglycerides accumulation and 8-isoprostane concentration and a reduction of insulin resistance were also observed in GK rats. Our data show that dietary restriction ameliorates systemic and skeletal muscle oxidative stress state in type 2 diabetes, which is associated with improved insulin resistance.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Blood Glucose; Cholesterol; Deoxyguanosine; Diabetes Mellitus, Type 2; Diet, Diabetic; Diet, Reducing; Dinoprost; Eating; Insulin Resistance; Male; Muscle, Skeletal; Oxidative Stress; Protein Carbonylation; Rats; Rats, Inbred OLETF; Rats, Wistar; Triglycerides

Insulin resistance is associated with hypertension by mechanisms likely involving the kidney. To determine how the major apical sodium transporter of the thick ascending limb, the bumetanide-sensitive Na-K-2Cl cotransporter (NKCC2) is regulated by high-fat feeding, we treated young male, Fischer 344 X Brown Norway (F344BN) rats for 8 wk with diets containing either normal (NF, 4%) or high (HF, 36%) fat, by weight, primarily as lard. HF-fed rats had impaired glucose tolerance, increased urine excretion of 8-isoprostane (a marker of oxidative stress), increased protein levels for NKCC2 (50-125%) and the renal outer medullary potassium channel (106%), as well as increased natriuretic response to furosemide (20-40%). To test the role of oxidative stress in this response, in study 2, rats were fed the NF or HF diet plus plain drinking water, or water containing N(G)-nitro-l-arginine methyl ester (l-NAME), a nitric oxide synthase inhibitor (100 mg/l), or tempol, a superoxide dismutase mimetic (1 mmol/l). The combination of tempol with HF nullified the increase in medullary NKCC2, while l-NAME with HF led to the highest expression of medullary NKCC2 (to 498% of NF mean). However, neither of these drugs dramatically affected the elevated natriuretic response to furosemide with HF. Finally, l-NAME led to a marked increase in blood pressure (measured by radiotelemetry), which was significantly enhanced with HF. Mean arterial blood pressure at 7 wk was as follows (mmHg): NF, 100 +/- 2; NF plus l-NAME, 122 +/- 3; and HF plus l-NAME, 131 +/- 2. Overall, HF feeding increased the abundance of NKCC2. Inappropriately high sodium reabsorption in the thick ascending limb via NKCC2 may contribute to hypertension with insulin resistance.

Topics: Animals; Antioxidants; Biomarkers; Blood Pressure; Blotting, Western; Crosses, Genetic; Cyclic N-Oxides; Dietary Fats; Dinoprost; Enzyme Inhibitors; Furosemide; Glucose Intolerance; Hypertension; Insulin Resistance; Kidney Medulla; Male; Natriuresis; NG-Nitroarginine Methyl Ester; Nitric Oxide; Nitric Oxide Synthase; Oxidative Stress; Potassium Channels, Inwardly Rectifying; Rats; Rats, Inbred BN; Rats, Inbred F344; Sodium Potassium Chloride Symporter Inhibitors; Sodium-Potassium-Chloride Symporters; Sodium-Potassium-Exchanging ATPase; Solute Carrier Family 12, Member 1; Spin Labels; Telemetry; Time Factors; Up-Regulation

The aim was to examine the role of cyclooxygenase (COX)-2-mediated inflammation in the development of obese linked insulin resistance and fatty liver. The rats were fed separately regular diet (CONT), high-fat diet (HFD) ad libitum, or energy restrictedly for 12 weeks. Rats fed HFD ad libitum were further divided into three subgroups co-treated with vehicle (HFa), or a selective COX-2 inhibitor celecoxib (HFa-Cel) or mesulid (HFa-Mes). Euglycemic hyperinsulinemic clamp (EHC) experiment was performed at the end of study. Another set of rats with similar grouping was further divided into those with a 4, 8, or 12-week intervention period for hepatic sampling. Body weight was increased significantly and similarly in HFa, HFa-Cel, and HFa-Mes. Time-dependent increases in plasma insulin, glucose, 8-isoprostanes, leptin levels, homeostasis model assessment of insulin resistance (HOMA-IR) and hepatic triglyceride contents shown in HFa were significantly reversed in HFa-Cel and HFa-Mes. During EHC period, the reduction in stimulation of whole body glucose uptake, suppression of hepatic glucose production and metabolic clearance rate of insulin shown in HFa were significantly reversed in HFa-Cel and HFa-Mes. The enhanced COX-2 and tumor necrosis factor-alpha (TNF-alpha) but attenuated PPAR-gamma and C/EBP-alpha mRNA expressions in epididymal fat shown in HFa were significantly reversed in HFa-Cel and HFa-Mes. The increases in average cell size of adipocytes and CD68 positive cells shown in HFa were also significantly reversed in HFa-Cel and HFa-Mes. Our findings suggest that COX-2 activation in fat inflammation is important in the development of insulin resistance and fatty liver in high fat induced obese rats.

Topics: Adipocytes; Adipogenesis; Adipose Tissue; Animals; Blood Glucose; Body Weight; Celecoxib; Cell Size; Cyclooxygenase 1; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Dinoprost; Disease Models, Animal; Fatty Liver; Insulin; Insulin Resistance; Leptin; Liver; Macrophages; Male; Membrane Proteins; Obesity; Panniculitis; Pyrazoles; Rats; Rats, Sprague-Dawley; Sulfonamides; Time Factors; Triglycerides; Tumor Necrosis Factor-alpha

In order to characterize whether different degrees of adipose tissue storage may be associated with markers of early atherosclerosis, we evaluated oxidant-antioxidant status and inflammatory markers and determined carotid intima-media thickness (cIMT) in healthy constitutional lean and obese pre-pubertal children.. Eighty healthy pre-pubertal lean and obese children were recruited and compared with 40 age, gender, and pubertal stage-matched normal controls. Anthropometric measurements, oxidant (urinary isoprostanes (PGF-2alpha), lag phase, and malondialdehyde (MDA)) and antioxidant status (vitamin E), inflammatory markers (high sensitive C-reactive protein (hs-CRP)), and insulin sensitivity (fasting glucose-insulin ratio, homeostasis model assessment of insulin resistance (HOMA-IR)) were investigated. Furthermore, cIMT was measured by high-resolution ultrasound.. hs-CRP was not different between lean and control subjects (P=0.45), while higher values were found in obese compared with lean and control children (P<0.001 and P<0.001 respectively). PGF-2alpha and MDA were higher while lag phase shorter in lean and obese subjects compared with controls (lean P<0.001; P<0.001; P<0.001 and obese P<0.001; P<0.001; P<0.001 respectively), while no differences were documented between lean and obese subjects (P=0.78, P=0.019, and P=0.53 respectively). Compared with controls, cIMT was increased in lean and in obese subjects (P=0.001; P=0.004), while no differences were documented between obese and lean subjects (P=0.1). In a multiple stepwise linear regression analysis, cIMT was related with PGF-2alpha (beta=0.641, P<0.001) and HOMA-IR (beta=0.307; P<0.001).. Pre-pubertal lean and obese children present increased oxidative stress and impaired inflammation and insulin sensitivity, which in turn seem to result in similar impaired endothelial dysfunction and early signs of atherosclerosis, already in childhood.

Topics: Antioxidants; Biomarkers; Body Weight; C-Reactive Protein; Carotid Arteries; Carotid Artery Diseases; Child; Chronic Disease; Dinoprost; Female; Humans; Inflammation; Insulin Resistance; Male; Malondialdehyde; Obesity; Oxidants; Regression Analysis; Severity of Illness Index; Tunica Intima; Ultrasonography; Vitamin E

Our aim was to evaluate the effect of BW and obesity on oxidative stress and IR in prepubertal SGA and LGA children compared with appropriate-for-gestational-age (AGA) children.. We performed a cross-sectional study comparing oxidative stress and IR in 103 children categorized into 6 groups according to BW (26 SGA, 15 AGA, and 16 LGA normal-weight children) and obesity (15 SGA, 15 AGA, and 16 LGA obese children). Indexes of IR (HOMA-IR, G/I) and the marker of oxidative stress (urinary isoprostanes) were evaluated.. Homeostasis Model Assessment was higher in both normal-weight SGA and LGA children than in normal-weight AGA children (all P

Topics: Anthropometry; Birth Weight; Child; Child, Preschool; Cross-Sectional Studies; Dinoprost; Female; Fetal Macrosomia; Humans; Infant; Infant, Newborn; Infant, Small for Gestational Age; Insulin Resistance; Isoprostanes; Longitudinal Studies; Male; Obesity; Oxidative Stress; Pregnancy; Reference Values; Regression Analysis; Risk Factors

This study was designed to examine the role of cyclooxygenase (COX) 2-mediated low-grade inflammation in the development of fructose-induced whole body and muscular insulin resistance in rats. The rats were on regular or fructose-enriched diets for 8 weeks. Fructose-fed rats were further divided into 3 groups (n = 8 per group). There were fructose-fed rats, fructose-fed rats with nimesulide (a selective COX2 inhibitor, 30 mg/kg/day, gavage) and fructose-fed rats with celecoxib (a selective COX2 inhibitor, 30 mg/kg/day, gavage). The present result showed that fructose-induced time-dependent increases in systolic blood pressure and fasting plasma insulin and triglyceride levels were significantly suppressed in rats treated with nimesulide or cerecoxib. The ratio of area under glucose curve divided by area under insulin curve obtained during the oral glucose tolerance test was significantly decreased in fructose-fed rats, which were markedly reversed in those co-treated with nimesulide or celecoxib. Accordingly, fructose-induced decrease in insulin-stimulated glucose uptake in soleus muscle was significantly reversed in those combined with nimesulide or celecoxib. Fructose-induced time-dependent increases in plasma 8-isoprostane and PGE metabolites were concomitantly suppressed by nimesulide or celecoxib co-treatment. The present study demonstrates that the COX2-mediated low-grade inflammation, especially mediated by increase in oxidative stress was important in the development of insulin resistance in fructose-fed rats.

Topics: Animals; Blood Pressure; Body Weight; Cyclooxygenase 2; Dinoprost; Disease Models, Animal; Fructose; Glucose; Glucose Tolerance Test; Hypoglycemic Agents; Inflammation; Insulin; Insulin Resistance; Male; Metabolic Syndrome; Muscle, Skeletal; Prostaglandins E; Rats; Rats, Sprague-Dawley; Sweetening Agents

Obesity in children appears to be associated with increased risk of cardiovascular and metabolic diseases later in life. Early development of insulin resistance and impaired oxidant-antioxidant status may lead to endothelial dysfunction and increased carotid intima media thickness (IMT) even in childhood. The aim of this study was to measure IMT and the relationship between IMT, insulin resistance and oxidant status in obese pre-pubertal children. In 53 obese pre-pubertal children (27M/26F, mean age 8+/-2 years), anthropometric measurements and inflammatory markers (hs-CRP and PGF-2 alpha), were evaluated compared with 41 healthy pre-pubertal subjects (21M/20F, mean age 7+/-2 years). OGTT was performed and insulin resistance (IR) indices (HOMA-IR, WBISI, G/I and QUICKI) were calculated in all patients. High-resolution ultrasound techniques were used to evaluate IMT. Obese children had higher levels of PGF-2 alpha and hs-CRP compared to healthy subjects (p=0.001 and p=0.005). Furthermore, fasting insulin levels and HOMA-IR were higher in obese children than in controls (p=0.001 and p=0.001) while WBISI was significantly lower (p=0.002). In addition, obeses had an increased IMT (p=0.001). In obese children there was a significant correlation between IMT and indices of IR (HOMA-IR: beta=-1.233, p=0.002; WBISI: beta=-0.921, p=0.008; G/I: beta=-0.811, p=0.003) and between IMT and PGF-2 alpha (beta=0.505, p=0.004). After categorizing subjects according to tertiles of body mass index (BMI) (or=26.23 kg/m(2)) and to waist circumference (WC) (or=79.04 cm), no influence of BMI or WC on IMT were found in the three groups. In conclusion, early changes in glucose metabolism and an alteration of oxidant-antioxidant status may be present in obese pre-pubertal children; this could lead to increase IMT and early cardiovascular disease.

Topics: Biomarkers; Blood Glucose; C-Reactive Protein; Carotid Artery Diseases; Child; Comorbidity; Dinoprost; Female; Humans; Insulin; Insulin Resistance; Male; Obesity; Oxidative Stress; Risk Factors; Tunica Intima; Tunica Media; Ultrasonography

Oxidative stress (OS) and inflammatory mediators increase with aging. The levels of advanced glycation endproducts (AGEs), prooxidant factors linked to chronic diseases such as diabetes, cardiovascular disease, and renal disease, also increase with aging. AGEs are readily derived from heat-treated foods. We propose that the excess consumption of certain AGEs via the diet enhances OS and inflammatory responses in healthy adults, especially in elderly persons.. We examined 172 young (<45 years old) and older (>60 years old) healthy individuals to determine whether the concentration of specific serum AGEs (N(epsilon)-carboxymethyl-lysine [CML] or methylglyoxal [MG] derivatives) were higher in older compared to younger persons and whether, independent of age, they correlated with the intake of dietary AGEs, as well as with circulating markers of OS and inflammation.. Body weight, body mass index (BMI), and serum AGE, CML, and MG derivatives were higher in older participants, independent of gender. Serum CML correlated with levels of 8-isoprostanes (r = 0.448, p =.0001) as well as with Homeostasis Model Assessment index (HOMA), an index of insulin resistance (r = 0.247, p =.044). The consumption of dietary AGEs, but not of calories, correlated independently with circulating AGEs (CML: r = 0.415, p =.0001 and MG: r = 0.282, p =.002) as well as with high sensitivity C-reactive protein (hsCRP) (r = 0.200, p =.042).. Circulating indicators of AGEs (CML and MG derivatives), although elevated in older participants, correlate with indicators of inflammation and OS across all ages. Indicators of both AGEs and OS are directly influenced by the intake of dietary AGEs, independent of age or energy intake. Thus, reduced consumption of these oxidants may prove a safe economic policy to prevent age-related diseases, especially in an aging population.

Topics: Adult; Aged; Aged, 80 and over; Aging; C-Reactive Protein; Diet; Dinoprost; Energy Intake; Female; Glycation End Products, Advanced; Humans; Inflammation; Insulin Resistance; Lysine; Male; Middle Aged; Oxidative Stress; Pyruvaldehyde

Systemic oxidative stress causes insulin resistance in rodents. We tested the hypothesis that oxidative stress and insulin resistance are associated in humans.. We used cross-sectional data from 2,002 nondiabetic subjects of the community-based Framingham Offspring Study. We measured insulin resistance with the homeostasis model and defined categorical insulin resistance as homeostasis model assessment of insulin resistance (HOMA-IR) > 75th percentile. We measured oxidative stress using the ratio of urine 8-epi-prostaglandin F2alpha (8-epi-PGF2alpha) to creatinine and used age- and sex-adjusted regression models to test the association of oxidative stress with insulin resistance in individuals without diabetes and among subgroups at elevated risk of diabetes.. Across 8-epi-PGF2alpha/creatinine tertiles, the prevalence of insulin resistance increased (18.0, 27.5, and 29.4% for the first, second, and third tertiles, respectively; P < 0.0001), as did mean levels of HOMA-IR (3.28, 3.83, and 4.06 units; P < 0.0001). The insulin resistance-oxidative stress association was attenuated by additional adjustment for BMI (P = 0.06 across tertiles for insulin resistance prevalence; P = 0.004 for mean HOMA-IR). Twenty-six percent of participants were obese (BMI > or = 30 kg/m2), 39% had metabolic syndrome (according to the Adult Treatment Panel III definition), and 37% had impaired fasting glucose (IFG) (fasting glucose 5.6-6.9 mmol/l). Among 528 obese participants, respectively, insulin resistance prevalence was 41.3, 60.6, and 54.2% across 8-epi-PGF2alpha/creatinine tertiles (P = 0.005); among 781 subjects with metabolic syndrome, insulin resistance prevalence was 41.3, 56.7, and 51.7% (P = 0.0025); and among 749 subjects with IFG, insulin resistance prevalence was 39.6, 47.2, and 51.6% (P = 0.04).. Systemic oxidative stress is associated with insulin resistance in individuals at average or elevated risk of diabetes even after accounting for BMI.

Topics: Aged; Biomarkers; Body Mass Index; Body Size; Cardiovascular Diseases; Creatinine; Diabetes Mellitus; Dinoprost; Female; Health Surveys; Humans; Insulin Resistance; Male; Massachusetts; Middle Aged; Nuclear Family; Oxidative Stress; Phenotype; Prediabetic State; Prevalence

Several studies have reported that insulin resistance and compensatory hyperinsulinemia increased lipid peroxidation, suggesting the linking to each other. We investigated the relationships between insulin resistance index HOMA-IR and lipid peroxidation, plasma antioxidant status in non-diabetic, hypercholesterolemic patients.. We measured the urinary excretion of 8-epi-prostaglandin F(2)(alpha)(PGF(2)(alpha)) levels as a measure of lipid peroxidation in vivo, total radical trapping antioxidant potential (TRAP) and fat-soluble antioxidant vitamins in 76 non-diabetic subjects with hypercholesterolemia (mean age 59 years, 25 males and 51 females). Insulin resistance was evaluated by homeostasis model assessment (HOMA-IR) derived from fasting glucose and insulin concentrations.. HOMA-IR was positively correlated with the urinary excretion of PGF(2)(alpha) (r=0.222, p<0.05) and negatively correlated with the TRAP (r=-0.211, p<0.05) in total subjects. Furthermore, there were significant inverse relationships between HOMA-IR and lipid corrected fat-soluble vitamins such as beta-carotene (r=-0.297, p<0.01) and gamma-tocopherol (r=-0.243, p<0.05) and also significant inverse relation was found between lipid corrected beta-carotene and the urinary PGF(2)(alpha)excretion (r=-0.205, p<0.05). When total subjects were divided into three groups according to tertiles of HOMA-IR, significant differences in urinary PGF(2)(alpha)excretion (p<0.05) and lipid corrected beta-carotene (p<0.005) among the three groups were observed. The highest HOMA-IR group had the higher levels of urinary PGF(2)(alpha)excretion and lower levels of plasma beta-carotene compared with the lowest HOMA-IR group.. Our data showed that the insulin resistance of hypercholesterolemic patients increased oxidative stress and negatively influenced plasma antioxidant system. These results provide evidence in understanding mechanism linking insulin resistance and oxidative stress accompanied by reduced antioxidant system.

Topics: Adult; Aged; Antioxidants; Blood Glucose; Dinoprost; Female; Health Status; Humans; Hypercholesterolemia; Insulin Resistance; Lipid Peroxidation; Male; Middle Aged; Oxidative Stress; Vitamins

Limited data are available on the association of insulin resistance, adipokines, and in vivo lipid peroxidation. We investigated the relationships between insulin resistance, adipokines (leptin, adiponectin, and resistin), and oxidative stress in nondiabetic, hypercholesterolemic patients. Seventy-six nondiabetic patients with hypercholesterolemia participated in this cross-sectional study. Fasting glucose and insulin concentrations were analyzed. Serum leptin, adiponectin, and resistin concentrations and urinary excretion of 8-epi-prostaglandin F(2alpha) (8-epi-PGF(2alpha)) were determined using enzyme-linked immunosorbent assay. We divided all subjects into 3 groups, classified by the tertiles of homeostasis model assessment of insulin resistance (HOMA-IR) values, and clinical parameter comparisons were made among the 3 groups. The results showed that serum leptin (P < .001) and adiponectin levels (P < .05) were significantly different among the groups, although serum resistin was not different. Furthermore, the group with the highest HOMA-IR had a significantly higher urinary 8-epi-PGF(2alpha) excretion than the group with the lowest HOMA-IR (P = .017). Circulating leptin was positively correlated with urinary 8-epi-PGF(2alpha) (r = 0.323, P < .01) and HOMA-IR (r = 0.524, P < .001). Circulating adiponectin was negatively correlated with body mass index (r = -0.252, P < .05) and HOMA-IR (r = -0.228, P < .05). We could not find a relationship between circulating adiponectin or resistin and urinary 8-epi-PGF(2alpha) excretion. Stepwise multiple linear regression analysis showed that leptin was associated with the urinary 8-epi-PGF(2alpha) excretion after adjusting for age, sex, body mass index, blood lipids, and HOMA-IR (P = .002). In conclusion, our results show that more insulin-resistant state of nondiabetic, hypercholesterolemic patients is associated with decreased adiponectin and increased leptin and urinary 8-epi-PGF(2alpha) levels, although no relationship with resistin was observed. Furthermore, serum leptin independently contributed to urinary 8-epi-PGF(2alpha) excretion.

Topics: Adiponectin; Adult; Aged; Body Mass Index; Dinoprost; Female; Humans; Hypercholesterolemia; Insulin Resistance; Leptin; Lipid Peroxidation; Male; Middle Aged; Oxidative Stress; Regression Analysis

Thirty-four children were assessed for body composition, blood pressure, lipids, glucose tolerance, markers of insulin resistance, oxidative stress, and adipokines. Children were divided into 3 groups: (1) normal weight, (2) overweight but otherwise healthy, and (3) overweight with the metabolic syndrome. There were no differences among any of the groups for age or Tanner stage, and anthropometric variables were similar between the overweight and the overweight with the metabolic syndrome groups. Differences across groups were found for high-density lipoprotein cholesterol (P < .001), triglycerides (P < .01), fasting insulin (P < .001), homeostasis model assessment (P < .01), adiponectin (P < .05), leptin (P < .0001), C-reactive protein (P < .0001), interleukin 6 (P < .0001), and 8-isoprostane (P < .001). In children, oxidative stress and adipokine levels worsen throughout the continuum of obesity and especially in the presence of components of the metabolic syndrome. Overweight children with components of the metabolic syndrome may be at elevated risk for future cardiovascular disease.

Topics: Adiponectin; Adolescent; Biomarkers; Blood Glucose; Blood Pressure; Body Composition; C-Reactive Protein; Cardiovascular Diseases; Child; Cholesterol, HDL; Dinoprost; Female; Humans; Insulin; Insulin Resistance; Interleukin-6; Leptin; Male; Metabolic Syndrome; Minnesota; Obesity; Oxidative Stress; Risk Assessment; Risk Factors; Triglycerides

We examined if administration of an antioxidant compound protects against the development of insulin resistance and hypertension. Male rats were assigned randomly into four groups, and treated for 12 weeks with normal chow, normal chow plus N-acetylcysteine (1.5 g/day/kg), fructose (60% of diet), and fructose plus N-acetylcysteine. After 10 weeks, plasma triglyceride and 15-F2t-isoprostane, and insulin sensitivity were measured, and after 12 weeks, pressor response to methoxamine (15-60 microg/kg min) was assessed. Relative to normal chow-fed controls, the fructose-fed rats had increased blood pressure, plasma insulin, triglyceride and 15-F2t-isoprostane, and decreased insulin sensitivity; these changes were inhibited by N-acetylcysteine. Maximal pressor response to methoxamine was attenuated in the fructose-fed rats given N-acetylcysteine relative to the other three groups. Therefore, chronic treatment with N-acetylcysteine increases insulin sensitivity and prevents the blood pressure increase associated with fructose feeding in rats, the mechanism may involve the decrease of oxidative stress and alpha-adrenoceptor-mediated vasoconstriction.

Topics: Acetylcysteine; Adrenergic alpha-Agonists; Animals; Blood Pressure; Dinoprost; Dose-Response Relationship, Drug; Fructose; Glucose Tolerance Test; Hypertension; Insulin Resistance; Male; Methoxamine; Random Allocation; Rats; Rats, Sprague-Dawley; Triglycerides

Oxidative stress and the gene expression at the transcriptional level of antioxidant enzymes were investigated in two models of diabetes in mice. We used KKAy mice as a model of obese insulin-resistant diabetes, and streptozotocin-induced diabetic mice (STZ mice) as a model of insulin-deficient diabetes. C57BL mice and saline-injected ICR mice were used as the respective non-diabetic controls. To assess oxidative damage, plasma malonedialdehyde (MDA), urine 8-isoprostane and 8-hydroxy deoxyguanosine (8-OHdG) were measured. The mRNA expression of antioxidant enzymes, superoxide dismutase 1 (SOD-1) and glutathione peroxidase 1 (GPx-1) in the kidney and heart were quantified using a real-time polymerase chain reaction. The KKAy mice demonstrated moderate hyperglycemia and hyperlipidemia, and the STZ mice showed severe hyperglycemia and hypolipidemia. The KKAy mice, but not the STZ mice, showed elevated plasma MDA relative to the non-diabetic controls. Urine 8-isoprostane and 8-OHdG in both diabetic mouse groups increased significantly. The urine oxidative stress markers in the severely hyperglycemic STZ mice were higher than those in the moderately hyperglycemic KKAy mice. Although GPx-1 and SOD-1 showed elevated mRNA expression in the KKAy mice in the kidney and heart, in the STZ mice they did not increase compared to the controls. The compensatory up-regulation of the mRNA expression of antioxidant enzymes may be impaired in the insulin-deficient severely hyperglycemic state.

Topics: Animals; Base Sequence; Diabetes Complications; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Dinoprost; Disease Models, Animal; DNA Primers; Gene Expression Regulation, Enzymologic; Glutathione Peroxidase; Insulin Resistance; Kidney; Male; Mice; Mice, Inbred C57BL; Mice, Inbred ICR; Mice, Mutant Strains; Myocardium; Obesity; Superoxide Dismutase

Dietary advanced glycosylation end products (AGEs) have been linked to insulin resistance in db/db(++) mice. To test whether dietary AGEs play a role in the progression of insulin resistance in normal mice fed high-fat diets, normal C57/BL6 mice were randomly assigned to high-fat diets (35% g fat), either high (HAGE-HF group; 995.4 units/mg AGE) or low (by 2.4-fold LAGE-HF group; 329.6 units/mg AGE) in AGE content for 6 months. Age-matched C57/BL6 and db/db(++) mice fed regular diet (5% g fat, 117.4 units/mg AGE) served as controls. After 6 months, 75% of HAGE-HF mice were diabetic and exhibited higher body weight (P < 0.001), fasting glucose (P < 0.001), insulin (P < 0.001), and serum AGEs (P < 0.01) than control mice, while none of the LAGE-HF mice were diabetic despite a similar rise in body weight and plasma lipids. The HAGE-HF group displayed markedly impaired glucose and insulin responses during glucose tolerance tests and euglycemic and hyperglycemic clamps and altered pancreatic islet structure and function compared with those of LAGE-HF mice, in which findings resembled those of control mice. The HAGE-HF group had more visceral fat (by two- and fourfold) and more AGE-modified fat (by two- and fivefold) than LAGE-HF and control mice, respectively. In the HAGE-HF group, plasma 8-isoprostane was higher (P < 0.01) and adiponectin lower (P < 0.001) than control mice, while in the LAGE-HF group, these were more modestly affected (P < 0.05). These results demonstrate that the development of insulin resistance and type 2 diabetes during prolonged high-fat feeding are linked to the excess AGEs/advanced lipoxidation end products inherent in fatty diets.

Topics: Adiponectin; Adipose Tissue; Animals; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Dietary Fats; Dinoprost; Fasting; Female; Glucose Clamp Technique; Glucose Tolerance Test; Glycation End Products, Advanced; Hyperplasia; Insulin; Insulin Resistance; Intercellular Signaling Peptides and Proteins; Islets of Langerhans; Lipids; Mice; Mice, Inbred C57BL

Topics: Blood Glucose; Body Mass Index; Body Weight; Dinoprost; Glucose Clamp Technique; Humans; Hyperinsulinism; Insulin Resistance; Japan; Male; Obesity; Oxidative Stress; Reference Values; Triglycerides

To examine the relationship between insulin resistance (IR) and the reduction of oxidative stress in vivo by the statin atorvastatin.. This study included 40 patients with hypercholesterolemia without a history of diabetes mellitus (21 males, 19 females, mean age 62 +/- 11 years). Homeostasis assessment insulin resistance (HOMA-IR) was used as a marker for insulin resistance. The patients were divided into two groups [IR group (n = 24) and non-IR group (n = 16), using the cut off level of 1.73]. Urinary 8-iso-prostaglandin F2alpha (U-8-iso) excretion was used as an oxidative stress marker. The subjects were treated with atorvastatin (10 mg/day) for 12 weeks.. The IR group had significantly higher U-8-iso levels than the non-IR group before atorvastatin administration (211 +/- 112 vs 137 +/- 33 pg/mg Cr, p = 0.01). Low-density lipoprotein cholesterol, triglyceride, and 8-iso levels were significantly reduced in both groups after 12 weeks, U-8-iso levels were significantly higher in the IR group than the non-IR group (178 +/- 61 vs 110 +/- 38 pg/mg Cr, p = 0.003), and HOMA-IR showed no significant change. Multiple regression analysis after 12 weeks showed that HOMA-IR and triglyceride levels were independent variables for U-8-iso levels (standard regression coefficient = 0.60, 0.59, p < 0.0001, p = 0.0002).. Insulin resistance is important in the occurrence of oxidative stress in patients with hypercholesterolemia. Since atorvastatin does not reduce insulin resistance, further therapy to reduce insulin resistance is necessary for early prevention of cardiovascular events during atorvastatin treatment.

Topics: Aged; Atorvastatin; Dinoprost; Female; Heptanoic Acids; Homeostasis; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Insulin Resistance; Lipids; Male; Middle Aged; Oxidative Stress; Pyrroles

The relationship between oxidative stress in vivo and insulin resistance was examined.. This study included 87 patients, 46 males and 41 females (mean age 63 +/- 10 years), without coronary artery disease. The homeostasis assessment insulin resistance (HOMA-IR) (fasting blood sugar x fasting immunoreactive insulin/405), a marker for insulin resistance, was measured. The patients were divided into three groups: the noninsulin resistance group (N-IR group) without diabetes mellitus (DM) and with fasting blood glucose level of 126 mg/dl and HOMA-IR < or = 1.73 (n = 44), the insulin resistance group (IR group) without diabetes mellitus and with fasting blood glucose level of 126 mg/dl and HOMA-IR > 1.73 (n = 29), and the DM group (type 2 diabetes mellitus) (n = 14). Urinary 8-iso-prostaglandin F2 alpha (U-8-iso-PGF2 alpha) excretion was measured as a marker of in vivo oxidative stress.. There were significantly more obese patients in the IR group than in the N-IR group (62% vs 25%, p = 0.001), and the remnant-like particle cholesterol level was significantly higher in the IR group than in the N-IR group (7.6 +/- 5.2 vs 4.6 +/- 1.5 mg/dl, p < 0.01). Patients in the IR group had a significantly larger number of coronary risk factors. U-8-iso-PGF2 alpha excretion was significantly higher in the IR group and DM groups (201 +/- 86, 191 +/- 136 vs 129 +/- 50 pg/mg. Cr, p < 0.0001, p = 0.01), and there was a significantly positive correlation between the number of coronary risk factors, fasting blood sugar and U-8-iso-PGF2 alpha concentration (correlation coefficient = 0.32, 0.37, p = 0.002, p = 0.0003). Multiple regression analysis showed that remnant-like particle cholesterol, fasting blood sugar and insulin resistance were independent factors for U-8-iso-PGF2 alpha concentration (p < 0.0001, p = 0.0007, p = 0.02).. Insulin resistance, remnant lipoprotein and hyperglyceridemia are deeply involved in oxidative stress in vivo.

Topics: Blood Glucose; Cholesterol; Diabetes Mellitus; Dinoprost; F2-Isoprostanes; Female; Homeostasis; Humans; Insulin Resistance; Lipoproteins; Male; Middle Aged; Oxidative Stress; Regression Analysis

To investigate the direct relationship of oxidative stress with obesity and insulin resistance in men, we measured the plasma levels of 8-epi-prostaglandin F2alpha (PGF2alpha) in 14 obese and 17 nonobese men and evaluated their relationship with body mass index; body fat weight; visceral, sc, and total fat areas, measured by computed tomography; and glucose infusion rate during a euglycemic hyperinsulinemic clamp study. Obese men had significantly higher plasma concentrations of 8-epi-PGF2alpha than nonobese men (P < 0.05). The plasma levels of 8-epi-PGF2alpha were significantly correlated with body mass index (r = 0.408; P < 0.05), body fat weight (r = 0.467; P < 0.05), visceral (r = 0.387; P < 0.05) and total fat area (r = 0.359; P < 0.05) in all (obese and nonobese) men. There was also a significant correlation between the plasma levels of 8-epi-PGF2alpha and glucose infusion rate in obese men (r = -0.552; P < 0.05) and all men (r = -0.668; P < 0.01). In all subjects, the plasma levels of 8-epi-PGF2alpha were significantly correlated with fasting serum levels of insulin (r = 0.487; P < 0.01). In brief, these findings showed that the circulating levels of 8-epi-PGF2alpha are related to adiposity and insulin resistance in men. Although correlation does not prove causation, the results of this study suggest that obesity is an important factor for enhanced oxidative stress and that this oxidative stress triggers the development of insulin resistance in men.

Topics: Adipose Tissue; Adult; Cholesterol; Dinoprost; F2-Isoprostanes; Humans; Insulin Resistance; Male; Obesity; Oxidative Stress

To measure oxidative stress, endothelial dysfunction and insulin resistance in Indian Mauritians at different stages of development of Type II (non-insulin-dependent) diabetes mellitus.. Plasma total 8-epi-PGF2alpha, an indicator of oxidative stress, was determined in age-matched subjects with normal glucose metabolism (n = 39), impaired glucose tolerance (n = 14), newly diagnosed diabetes (n = 8) and established diabetes (n = 14). Plasma glucose and insulin were measured at baseline and 2 h following an oral glucose tolerance test. Endothelial function was assessed by non-invasive digital pulse wave photoplethysmography.. Plasma 8-epi-PGF2alpha increased in subjects with impaired glucose tolerance (p < 0.05) compared with control subjects, and was even higher in newly diagnosed diabetic patients (p < 0.01) and established (p < 0.01) diabetic patients. A tendency towards reduced endothelial function in subjects with impaired glucose tolerance became significant in patients with newly diagnosed and established diabetes (p < 0.01), and was correlated with 8-epi-PGF2alpha (r = 0.36, p < 0.01). Insulin resistance (homeostasis model assessment) did not change in subjects with impaired glucose tolerance compared with control subjects, but increased in newly diagnosed (p < 0.01) and established (p < 0.001) diabetic subjects. The 8-epi-PGF2alpha was correlated with fasting glucose (r = 0.50, p < 0.001), triglycerides (r = 0.40, p < 0.001) and insulin resistance (r = 0.35, p < 0.001).. Oxidant stress is an early event in the evolution of Type II diabetes and could precede the development of endothelial dysfunction and insulin resistance.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Dinoprost; Endothelium, Vascular; F2-Isoprostanes; Fasting; Female; Glucose; Glucose Intolerance; Humans; India; Insulin Resistance; Male; Mauritius; Middle Aged; Oxidative Stress; Reference Values; Triglycerides

We have concurrently investigated oxidant stress, glucose tolerance and glucose-stimulated insulin responses in the obese Zucker rat, a widely used model of insulin resistance. The plasma level of the lipid peroxidation product 8-epi-prostaglandin F2alpha, a sensitive in vivo marker of oxidant stress, was elevated approximately 5-fold in 13-week old obese relative to age-matched, insulin-sensitive lean Zucker rats. Supplementation of the diet with vitamin E (as (+)-alpha-tocopherol acetate, 0.5% w/w) for 4 weeks, reduced plasma 8-epi-prostaglandin F2alpha and concomitantly reversed glucose-stimulated hyperinsulinaemia in the obese Zucker rat without worsening glucose tolerance. We therefore provide evidence of oxidant stress, measured as elevated plasma 8-epi-prostaglandin F2alpha, for the first time in the obese Zucker rat which now provides a rationale for the beneficial effects of antioxidants on insulin action previously reported in this model of insulin resistance.

Topics: Animals; Blood Glucose; Body Weight; Dietary Supplements; Dinoprost; Hyperglycemia; Hyperinsulinism; Insulin; Insulin Resistance; Male; Obesity; Oxidative Stress; Rats; Rats, Zucker; Vitamin E