Vascular insulin resistance: a potential link between cardiovascular and metabolic diseases.
The physiologic actions of insulin in the vasculature serve to couple regulation of metabolic and hemodynamic homeostasis. Insulin activation of the phosphatidylinositol-3-kinase (PI3K) pathway promotes glucose uptake in insulin-responsive tissues and nitric oxide (NO) production in the endothelium. NO induces vasodilation and inhibits platelet aggregation and vascular smooth muscle cell growth. In contrast, insulin activation of the mitogen-activated protein kinase (MAPK) leads to vasoconstriction and pathologic vascular cellular growth. In states of insulin resistance, insulin activation of PI3K is selectively impaired, whereas the MAPK pathway is spared and activated normally. In the endothelium, selective impairment of insulin-mediated NO production may contribute to the development of hypertension, endothelial dysfunction, atherogenesis, and insulin resistance. This article reviews experimental and clinical data elucidating the physiologic and pathophysiologic role of insulin in the vasculature and the mechanisms contributing to the development of vascular and metabolic diseases.
Schulman
Ivonne Hernandez
IH
Vascular Biology Institute, University of Miami Miller School of Medicine, Veterans Affairs Medical Center, Nephrology-Hypertension Section, 1201 Northwest 16th Street, Miami, FL 33125, USA. ischulman@med.miami.edu
Zhou
Ming-Sheng
MS
D001808:Blood Vessels / Q000503:physiopathology; D002318:Cardiovascular Diseases / Q000503:physiopathology*; D006801:Humans; D007328:Insulin / Q000502:physiology*; D007333:Insulin Resistance / Q000502:physiology*; D008659:Metabolic Diseases / Q000503:physiopathology*; D014655:Vascular Resistance / Q000502:physiology*
D007328:Insulin