Roles of insulin, age, and asymmetric dimethylarginine, on nitric oxide synthesis in vivo.

We tested the effects of insulin, on production of NO-related substances (nitrites and nitrates, NOx) following 15N-arginine iv infusion, and on ADMA and SDMA concentrations, in conditions reportedly associated with altered NO availability, i.e. ageing, hypertension, hypercholesterolemia, and Type-2 Diabetes (T2DM). A total of 26 male subjects (age: 23-71 yrs, BMI: 23-33 kg/m2), some of them affected by mixed pathologic features, were enrolled. NOx fractional synthesis rate (FSR) was lower in elderly (p<0.015) and T2DM subjects p<0.03), than in matched controls. Hyperinsulinemia generally increased both NOx FSR and ASR (Absolute Synthesis Rate), and reduced NOx, ADMA and SDMA concentrations. Insulin-sensitivity was impaired only in T2DM. Using simple linear regression analysis across all subjects, age was inversely correlated with both NOx FSR (R2 = 0.23, p<0.015) and ASR (R2 = 0.21, p<0.02). NOx FSR inversely correlated with both ADMA and SDMA. Using multiple regression analysis and various models, NOx FSR remained inversely associated with age and ADMA, whereas ASR was inversely associated with age and diabetes. No association with insulin sensitivity was found. We conclude that whole-body NOx production is decreased in ageing and T2DM. Age, ADMA concentration and T2DM, but not insulin-resistance, appear as negative regulators of whole-body NOx production.