Effects of acute hyperinsulinemia on skeletal muscle mitochondrial function, reactive oxygen species production, and metabolism in premenopausal women.

BACKGROUND: Acute metabolic demands that promote excessive and/or prolonged reactive oxygen species production may stimulate changes in mitochondrial oxidative capacity. PURPOSE: To assess changes in skeletal muscle H2O2 production, mitochondrial function, and expression of genes at the mRNA and protein levels regulating energy metabolism and mitochondrial dynamics following a hyperinsulinemic-euglycemic clamp in a cohort of 11 healthy premenopausal women. METHODS: Skeletal muscle biopsies of the vastus lateralis were taken at baseline and immediately following the conclusion of a hyperinsulinemic-euglycemic clamp. Mitochondrial production of H2O2 was quantified fluorometrically and mitochondrial oxidation supported by pyruvate, malate, and succinate (PMS) or palmitoyl carnitine and malate (PCM) was measured by high-resolution respirometry in permeabilized muscle fiber bundles. mRNA and protein levels were assessed by real time PCR and Western blotting. RESULTS: H2O2 emission increased following the clamp (P<0.05). Coupled respiration (State 3) supported by PMS and the respiratory control ratio (index of mitochondrial coupling) for both PMS and PCM were lower following the clamp (P<0.05). IRS1 mRNA decreased, whereas PGC1α and GLUT4 mRNA increased following the clamp (P≤0.05). PGC1α, IRS1, and phosphorylated AKT protein levels were higher after the clamp compared to baseline (P<0.05). CONCLUSIONS: This study demonstrated that acute hyperinsulinemia induced H2O2 production and a concurrent decrease in coupling of mitochondrial respiration with ATP production in a cohort of healthy premenopausal women. Future studies should determine if this uncoupling ameliorates peripheral oxidative damage, and if this mechanism is impaired in diseases associated with chronic oxidative stress.

Antioxidant and renoprotective effects of sphingosylphosphorylcholine on contrast-induced nephropathy in rats.

Contrast induced nephropathy (CIN) is a major cause of morbidity, and increased costs as well as an increased risk of death. This study was evaluated effects of exogenous sphingosylphosphorylcholine (SPC) administration on CIN in rats. Eight animals were included in each of the following eight groups: control, control phosphate-buffered solution (PBS), control SPC 2, control SPC 10, CIN, CIN PBS, CIN SPC 2 and CIN SPC 10. The induced nephropathy was created by injected with 4 g iodine/kg body weight. SPC was administered 3 d at a daily two different doses of 2 µm/mL and 10 µm/mL intraperitoneally. The severity of renal injury score was determined by the histological and immunohistochemical changes in the kidney. Malondialdehyde (MDA), nitric oxide (NO) and superoxide dismutase (SOD) were determined to evaluate the oxidative status in the renal tissue. Treatment with 2 and 10 µM SPC inhibited the increase in renal MDA, NO levels significantly and also attenuated the depletion of SOD in the renal injuryCIN. These data were supported by histopathological findings. The inducible nitric oxide synthase positive cells and apoptotic cells in the renal tissue were observed to be reduced with the 2 and 10 µM SPC treatment. These findings suggested that 2 and 10 µM doses can attenuate renal damage in contrast nephropathy by prevention of oxidative stress and apoptosis. The low and high dose SPC may be a promising new therapeutic agent for CIN.

Relation between indices of end-organ damage and mean platelet volume in hypertensive patients.

Mean platelet volume (MPV) has been recognized as an independent risk factor of hypertension. Hypertensive end-organ damage worsens the prognosis in hypertensive patients. We aimed to investigate the relationship between MPV levels and subclinical end-organ damage in hypertensive patients. One hundred and sixteen hypertensive patients (81 women, 35 men, with a mean age of 53 ± 11) were included in the study. There was no correlation between MPV and left-ventricular mass index (LVMI) (r = 0.145; P = 0.14) or albuminuria (r = 0.009; P = 0.93). Among the individuals that had grade I and grade II retinopathy, MPV levels (8.3 ± 2 fL, 8.2 ± 1.3 fL; P = 0.28) were similar either. We concluded that there was no correlation between MPV and markers of end-organ damage in hypertensive patients.

The relationship between mean platelet volume with metabolic syndrome in obese individuals.

The metabolic syndrome is closely associated with atherosclerotic risk factors and increased mortality. Mean platelet volume (MPV) is an indicator of platelet activation which also shows a close relationship with cardiovascular risk factors, such as diabetes mellitus, hypertension, hypercholesterolemia, obesity, metabolic syndrome. The aim of this study was to investigate the correlates of metabolic syndrome, its components and MPV adjusted for obesity in a large population study. A total of 2298 individuals with a mean age of 50 (age range 18-92) were interviewed. Nine hundred and twenty obese participants, who had BMI 30 kg/m² or more, further evaluated for the presence of metabolic syndrome. Five hundred and thirteen [396 women (70.2%)] had metabolic syndrome and the rest 407 individuals [324 women (79.6%)] served as the control group. The BMI, SBP, DBP, waist circumference, fasting plasma glucose, visceral fat, total cholesterol, high-density lipoprotein-cholesterol, and triglyceride was higher significantly in metabolic syndrome group (P = 0.002 for BMI and P < 0.001 for the others). No significant difference was observed between groups regarding low-density lipoprotein cholesterol, white blood cells, platelet counts, MPV, hematocrit and hemoglobin (P > 0.05 for all). The presence of metabolic syndrome and its components do not constitute a difference in MPV values in obese patients with a BMI 30 kg/m² or more.

Normal range of mean platelet volume in healthy subjects: Insight from a large epidemiologic study.

AIM: Mean platelet volume (MPV) in the healthy population has not been studied before. Therefore, the aim of the study was to measure MPV in normal subjects in a large cohort of Turkish adults. METHODS: A total of 2298 subjects with a mean age of 50 (age range 18 to 92) were interviewed. Subjects who had smoking habit, diabetes, hypertension, coronary artery disease, dyslipidemia, chronic obstructive pulmonary disease, cancer, chronic use of any drugs including antiplatelets, heavy drinkers, metabolic syndrome, ejection fraction <55%, creatinine >1.4 in men and >1.1 in women, abnormal liver function tests and an abnormal TSH were excluded in a in a stepwise manner. Complete blood counts were done on the same day within 6 hours by a CELL-DYN 3700 SL analyzer (Abbott Diagnostics). RESULTS: Three hundred twenty-six participants (204 females (63%) and 122 males (37%) with a mean age of 41 ± 16) constituted the final healthy cohort. Mean MPV of the cohort was 8.9 ± 1.4 fL. There was no significant difference among age groups regarding MPV. CONCLUSION: Ninety-five percent of the individuals had a MPV between 7.2 and 11.7 fL. A patient having a MPV beyond this range should be evaluated carefully especially for occlusive arterial diseases.