The renin-angiotensin system and insulin resistance.

Insulin resistance upregulates the renin-angiotensin system (RAS), which contributes to the pathogenesis of hypertension, heart failure, and atherosclerosis. RAS inhibition decreases cardiovascular and renal morbidity and mortality and the incidence of new-onset type 2 diabetes. To the same degree, angiotensin II impairs insulin signaling, induces inflammation via the nuclear factor-kappaB pathway, and reduces nitric oxide availability and facilitates vasoconstriction, leading to insulin resistance and endothelial dysfunction. Thus, the RAS, insulin resistance, and inflammation perpetuate each other and coordinately contribute to endothelial dysfunction, vascular injury, and atherosclerosis.