Insulin effects on blood flow

Insulin, at physiologic concentrations, increases skeletal muscle blood flow in lean insulin-sensitive subjects. This insulin effect is blunted in states of insulin resistance such as obesity and type 2 diabetes mellitus. Whether insulin-mediated increments in blood flow augment insulin-mediated glucose uptake and whether impaired insulin-mediated vasodilation contributes to decreased rates of insulin-mediated glucose uptake (insulin resistance) are still debated. Recently, positron emission tomography scanning and microdialysis have been applied to answer the question. It has been demonstrated that insulin’s effect on blood flow is mediated through the release of endothelium-derived nitric oxide, the most potent endogenous vasodilator, and that insulin modulates the response to other vasoactive hormones also at the level of the vascular smooth muscle cell. Importantly, nitric oxide is not only a vasodilator but also exhibits a host of anti-atherosclerotic properties. Because impaired insulin-mediated vasodilation in obesity and type 2 diabetes suggested decreased production of nitric oxide, recent research has focused on vascular endothelial function in insulin-resistant states. There is now good evidence for impaired endothelial function and decreased nitric oxide production in obesity and type 2 diabetes. The mechanism(s) by which obesity and type 2 diabetes impair endothelial function have not been fully elucidated but elevated free fatty acid levels as observed in these insulin resistant subjects may account, at least in part, for the vascular dysfunction.