Insulin action and insulin resistance in vascular endothelium

Curr Opin Clin Nutr Metab Care. 2007 Jul;10(4):523-30. doi: 10.1097/MCO.0b013e32819f8ecd.

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.

Publication types

  • Research Support, N.I.H., Intramural
  • Review

MeSH terms

  • Cardiovascular Physiological Phenomena
  • Cardiovascular System / drug effects*
  • Cardiovascular System / metabolism
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / metabolism
  • Humans
  • Insulin / metabolism
  • Insulin / pharmacology
  • Insulin / physiology*
  • Insulin Resistance*
  • Nitric Oxide / metabolism
  • Signal Transduction

Substances

  • Insulin
  • Nitric Oxide