Obesity, insulin resistance, and skeletal muscle nitric oxide synthase

12, 2012; doi:10.1152/japplphysiol.01018.2011.—The molecular mech-anisms responsible for impaired insulin action have yet to be fully identified. Rodent models demonstrate a strong relationship between insulin resistance and an elevation in skeletal muscle inducible nitric oxide synthase (iNOS) expression; the purpose of this investigation was to explore this potential relationship in humans. Sedentary men and women were recruited to participate (means SE: nonobese, body mass index 25.5 0.3 kg/m2, n 13; obese, body mass index 36.6 0.4 kg/m2, n 14). Insulin sensitivity was measured using an intravenous glucose tolerance test with the subsequent modeling of an insulin sensi-tivity index (SI). Skeletal muscle was obtained from the vastus lateralis, and iNOS, endothelial nitric oxide synthase (eNOS), and neuronal nitric oxide synthase (nNOS) content were determined by Western blot. SI was significantly lower in the obese compared with the nonobese group (43%; P 0.05), yet skeletal muscle iNOS protein expression was no