Reviews in Endocrine and Metabolic Disorders

, Volume 14, Issue 1, pp 5–12

Role of insulin resistance in endothelial dysfunction


  • Ranganath Muniyappa
    • Clinical Endocrine Section, Diabetes, Endocrinology, and Obesity Branch, National Institute of Diabetes and Digestive and Kidney DiseasesNational Institutes of Health
    • Departments of Internal Medicine and Medical Pharmacology and PhysiologyUniversity of Missouri School of Medicine
    • Harry S. Truman Memorial Veterans’ Hospital
    • Department of Internal MedicineUniversity of Missouri School of Medicine

DOI: 10.1007/s11154-012-9229-1

Cite this article as:
Muniyappa, R. & Sowers, J.R. Rev Endocr Metab Disord (2013) 14: 5. doi:10.1007/s11154-012-9229-1


Insulin resistance is frequently associated with endothelial dysfunction and has been proposed to play a major role in cardiovascular diseases. Insulin exerts pro- and anti-atherogenic actions on the vasculature. The balance between nitric oxide (NO)-dependent vasodilator actions and endothelin-1- dependent vasoconstrictor actions of insulin is regulated by phosphatidylinositol 3-kinase-dependent (PI3K) - and mitogen-activated protein kinase (MAPK)-dependent signaling in vascular endothelium, respectively. During insulin-resistant conditions, pathway-specific impairment in PI3K-dependent signaling may cause imbalance between production of NO and secretion of endothelin-1 and lead to endothelial dysfunction. Insulin sensitizers that target pathway-selective 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 anti-atherogenic actions of insulin.


Nitric oxide Insulin resistance Endothelial dysfunction Metabolic syndrome

Copyright information

© Springer Science+Business Media New York 2013