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Role of insulin resistance in endothelial dysfunction

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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 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.

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Acknowledgments

This 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 J.R.S. is supported by NIH (R01 HL73101-08 and R01 HL107910-03) and Veterans Affairs Merit System 0018.

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  1. Clinical Endocrine Section, Diabetes, Endocrinology, and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA

    Ranganath Muniyappa

  2. Departments of Internal Medicine and Medical Pharmacology and Physiology, University of Missouri School of Medicine, Columbia, MO, USA

    James R. Sowers

  3. Harry S. Truman Memorial Veterans’ Hospital, Columbia, MO, USA

    James R. Sowers

  4. Department of Internal Medicine, University of Missouri School of Medicine, One Hospital Drive, Columbia, MO, 65212, USA

    James R. Sowers

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Muniyappa, R., Sowers, J.R. Role of insulin resistance in endothelial dysfunction. Rev Endocr Metab Disord 14, 5–12 (2013). https://doi.org/10.1007/s11154-012-9229-1

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