Insulin Resistance and Endothelial Dysfunction: Macro and Microangiopathy

Abstract

Insulin has multiple metabolic actions, including effects on blood vessels. Insulin normally increases blood flow by a mechanism which involves generation of nitric oxide (NO) via the arginine–NO pathway. Although insulin itself is a weak and physiologically unimportant vasodilatator, it appears to markedly potentiate endothelium-dependent vasodilatation. Therefore, anything that impairs insulin action in endothelial cells can be expected to be associated with endothelial dysfunction, i.e. loss of NO bioactivity in the vessel wall. Consistent with the idea that insulin resistance and endothelial dysfunction frequently coexist, all insulin-resistant conditions examined to date have been associated with endothelial dysfunction. However, the latter can also be caused by factors other than insulin resistance—such as a high concentration of low-density lipoprotein (LDL) cholesterol. Therapies which reverse insulin resistance—such as exercise, insulin and inhibitors of the renin-angiotensin-aldosterone (RAA) axis—also reverse endothelial dysfunction, which may thus be an inherent feature of insulin resistance.