Role of insulin resistance in endothelial dysfunct

Authors: Ranganath Muniyappa James R Sowers

Publish Date: 2013/01/10

Volume: 14, Issue: 1, Pages: 5-12

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Abstract

Insulin resistance is frequently associated with endothelial dysfunction and has been proposed to play a major role in cardiovascular diseases Insulin exerts pro and antiatherogenic actions on the vasculature The balance between nitric oxide NOdependent vasodilator actions and endothelin1 dependent vasoconstrictor actions of insulin is regulated by phosphatidylinositol 3kinasedependent PI3K and mitogenactivated protein kinase MAPKdependent signaling in vascular endothelium respectively During insulinresistant conditions pathwayspecific impairment in PI3Kdependent signaling may cause imbalance between production of NO and secretion of endothelin1 and lead to endothelial dysfunction Insulin sensitizers that target pathwayselective impairment in insulin signaling are known to improve endothelial dysfunction In this review we discuss the cellular mechanisms in the endothelium underlying vascular actions of insulin the role of insulin resistance in mediating endothelial dysfunction and the effect of insulin sensitizers in restoring the balance in pro and antiatherogenic actions of insulinThis work was supported by the Intramural Research Program of National Institute of Diabetes and Digestive and Kidney Diseases National Institutes of Health NIH The research of JRS is supported by NIH R01 HL7310108 and R01 HL10791003 and Veterans Affairs Merit System 0018

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