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Review
, 10 (4), 523-30

Insulin Action and Insulin Resistance in Vascular Endothelium

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Review

Insulin Action and Insulin Resistance in Vascular Endothelium

Ranganath Muniyappa et al. Curr Opin Clin Nutr Metab Care.

Abstract

Purpose of review: Vasodilator actions of insulin are mediated by phosphatidylinositol 3-kinase dependent insulin signaling pathways in endothelium, which stimulate production of nitric oxide. Insulin-stimulated nitric oxide mediates capillary recruitment, vasodilation, increased blood flow, and subsequent augmentation of glucose disposal in skeletal muscle. Distinct mitogen-activated protein kinase dependent insulin signaling pathways regulate secretion of the vasoconstrictor endothelin-1 from endothelium. These vascular actions of insulin contribute to the coupling of metabolic and hemodynamic homeostasis that occurs under healthy conditions. Insulin resistance is characterized by pathway-specific impairment in phosphatidylinositol 3-kinase dependent signaling in both metabolic and vascular insulin target tissues. Here we discuss consequences of pathway-specific insulin resistance in endothelium and therapeutic interventions targeting this selective impairment.

Recent findings: Shared causal factors such as glucotoxicity, lipotoxicity, and inflammation selectively impair phosphatidylinositol 3-kinase dependent insulin signaling pathways, creating reciprocal relationships between insulin resistance and endothelial dysfunction. Diet, exercise, cardiovascular drugs, and insulin sensitizers simultaneously modulate phosphatidylinositol 3-kinase and mitogen-activated protein kinase dependent pathways, improving metabolic and vascular actions of insulin.

Summary: Pathway-specific impairment in insulin action contributes to reciprocal relationships between endothelial dysfunction and insulin resistance, fostering clustering of metabolic and cardiovascular diseases in insulin-resistant states. Therapeutic interventions that target this selective impairment often simultaneously improve both metabolic and vascular function.

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