Endothelial nitric oxide production and insulin sensitivity - A physiological link with implications for pathogenesis of cardiovascular disease

Background Insulin sensitivity varies up to threefold in apparently healthy individuals, but the mechanism for this is unknown. We have examined the hypothesis that vascular endothelial nitric oxide production and insulin sensitivity are directly related in humans. Methods and Results Nineteen healthy male subjects were studied on 3 separate days 1 week apart during which time they underwent measurement of insulin sensitivity by the euglycemic hyperinsulinemic clamp technique (soluble insulin 1.5 mU . kg(-1). min(-1)) and measurement of in vivo basal and stimulated endothelial nitric oxide production by forearm venous occlusion plethysmography. There was a correlation between insulin sensitivity and forearm vasoconstrictor responses to N-G-monomethyl-L-arginine, the substrate inhibitor of nitric oxide synthase (r=.52, P<.05). No correlations were observed between insulin sensitivity and noradrenaline, acetylcholine, or sodium nitroprusside responses. Conclusions Endothelial nitric oxide synthesis and insulin sensitivity are positively related in healthy humans, which suggests a direct physiological link.