The impact of insulin resistance on pathogenesis of cardiovascular disease

Abstract

Insulin resistance refers to the diminished response of insulin-sensitive tissues to insulin signaling. Recent observational studies increasingly indicate that insulin resistance may be one of the risk factors for the development of cardiovascular disease. The article focuses on the molecular basis of this phenomenon. In insulin resistance, hyperinsulinemia is observed, followed by impaired glucose metabolism, which subsequently leads to the development of inflammation due to triggering inflammatory signaling pathways and production of pro-inflammatory cytokines. Inflammation contributes to the formation of reactive oxygen species, which further exacerbate insulin resistance and promote the formation of atherosclerotic plaques. In turn reactive oxygen species indirectly contribute to reduced endothelial NO production, leading to vasoconstriction and increased blood pressure. Insulin resistance also stimulates vascular smooth muscle hypertrophy, a key contributor to hypertension and cardiovascular disease.