The Coupling of Glucose Metabolism and Perfusion in Human Skeletal Muscle: The Potential Role of Endothelium-Derived Nitric Oxide

Insulin-mediated glucose metabolism in skeletal muscle is associated with a commensurate increase in muscle perfusion. The link between insulin action and vasodilation may be mediated by endothelium-derived nitric oxide (EDNO). The evidence suggests that insulin causes an increase in the production of EDNO in insulin-sensitive but not insulin-resistant subjects. This defect in insulinmediated vasodilation may contribute to 1) enhanced presser sensitivity and 2) reduced rates of insulin-mediated glucose uptake. We propose that the endothelium is an insulin target tissue that exhibits an increase in the release of EDNO in response to insulin. We postulate that the insulin-resistant state of obesity is associated with insulin resistance at the level of the endothelium, reduced EDNO release, and impaired vasodilation. Thus EDNO may act as the mediator coupling glucose metabolism to vasodilation. The interaction between insulin and the endothelium to enhance EDNO release describes a novel insulin action that deserves further exploration.