Insulin action in the vasculature: Physiology and pathophysiology

Studies to date have provided convincing evidence that insulin has an impor tant role in the normal functioning of the vasculature from the perspective of the regulated delivery of nutrients to a tissue bed. This is mediated b y an effect on the endothelium analogous to other endothelial responses, an d insulin resistance is reflected in, and in part due to, impaired vasodila tory actions of insulin. Because insulin normally stimulates the net produc tion of nitric oxide, which is beneficial in both the short term for vasomo tion and antithrombosis, and the long term for inhibition of smooth muscle cell growth and migration, vascular insulin resistance also has important i mplications for vascular pathophysiology. Further, recent evidence suggests that the hyperinsulinemia accompanying insulin resistance may aggravate th is situation by augmenting the endothelial production and release of endoth elin-1. The investigation of insulin resistance in the vasculature provides not only a unique and physiologically relevant window onto vascular pathol ogy, but also an opportunity for therapeutic targeting in individuals affec ted by the clinical states of insulin resistance. The present review highli ghts the importance of insulin sensitivity in the maintenance of endothelia l function and explores the relationships between vascular insulin resistan ce and whole body glucose disposal. In addition, the recent evidence linkin g insulin to endothelin-1 production is discussed. Improving insulin sensit ivity with insulin sensitizers such as rosiglitazone may represent an impor tant advance in our ability to improve vascular dysfunction in diabetes. In troduction Copyright (C) 2001 S. Karger AG, Basel.