Vascular reactivity

Endothelial dysfunction appears to be an integral aspect of the insulin res istance syndrome, independently of hyperglycemia. The ability of insulin to cause endothelium-derived nitric oxide (NO)-dependent vasodilation amplifi es its overall effect of stimulating skeletal muscle glucose uptake and mod ulating vascular tone, The dose-dependent physiologic increase in skeletal muscle blood flow in response to insulin, which is highly associated with t he rate of glucose metabolism, is impaired in insulin-resistant states. Ins ulin appears to mediate vasodilation by direct stimulation bf release of NO from endothelium. Studies of the response to the endothelium-dependent vas odilator methacholine chloride in lean and obese nondiabetic subjects and o bese subjects with type 2 diabetes mellitus indicate that there may be mark ed endothelial dysfunction very early in insulin resistance, The potent vas oprotective effects of NO mitigate various atherogenic processes, including vascular smooth muscle cell proliferation, platelet adhesion and thromboge nesis, lipid peroxidation, and monocyte adhesion to endothelial cells. The interaction between insulin and NO may contribute to the prominent outcomes of insulin resistance syndrome (viz,, hypertension, thrombosis, and athero sclerosis), (C) 1999 by Excerpta Medico, Inc.