Insulin-mediated activation of the L-arginine nitric oxide pathway in man, and its impairment in diabetes

AIMS/HYPOTHESIS: Impaired L-arginine transport has been reported in cardiovascular diseases, providing a possible mechanism for reduced nitric oxide (NO) production. Given that cardiovascular diseases are also associated with insulin resistance, and insulin is known to induce vasodilation via a NO-dependent pathway, we hypothesised that abnormal insulin modulation of L-arginine transport may contribute to vascular dysfunction in diabetes. METHODS: Forearm blood flow (FBF) responses to insulin and sodium nitroprusside (SNP) were measured in control and type 2 diabetic volunteers using venous occlusion plethysmography. Effects of intra-arterial insulin on the forearm veno-arterial flux of arginine and related amino acids were determined by HPLC. The effect of locally delivered insulin on arginine transport was assessed during an intra-arterial infusion of [4,5-(3)H] L-arginine. RESULTS: In controls, intrabrachial infusion of 5 mUnits/min insulin lead to a progressive rise in FBF (p