Nitric Oxide and Endothelial Dysfunction

Several groups have shown that insulin-resistant subjects have a reduced insulin-stimulated increase in leg blood flow; the changes in peripheral blood flow were closely associated with the degree of insulin resistance (22,32-35). This endothelial dysfunction is demonstrated not only in patients with type 2 diabetes but also in nondiabetic subjects, such as obese adolescents or first-degree relatives of patients with type 2 diabetes (33,35,36).

It seems that peripheral blood flow is augmented via an insulin-mediated NO-dependent process (Fig. 3), and inhibition of NO formation prevents the

insulin-induced increase in blood flow (37). Thus, NO could indirectly affect insulin sensitivity as it increases peripheral blood flow and subsequent substrate delivery to the skeletal muscle. However, there is still a debate about the clinical relevance of these findings.

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