The vascular endothelium, a benign restrictive barrier? No! Role of nitric oxide in regulating insulin action

Insulin resistance is the primary abnormality associ-ated with obesity, type 2 diabetes, and hypertension(1,2). Interestingly, these disease processes alsoshare a common underlying impairment of vascular endothelial function. For many years the endothelium was thought of as nothing more than a benign barrier between blood and extracellular space. But intensive investigations demonstrate a myriad of actions by the endothelium, in-cluding regulation of blood flow (3,4), vascular tone (5), vascular permeability (6), and the immune response (7). The capillary endothelium regulates blood flow via the release of several vasoactive agents, in particular nitric oxide (NO) (8). Baron (4) first demonstrated that insulin can stimulate the release of endothelial NO, thereby reg-ulating blood flow and its own delivery. Insulin has mul-tiple hemodynamic actions to enhance its ability to increase glucose uptake in skeletal muscle (4, 9–11). The three major methods include: 1) increasing blood flow t