An integrated view of insulin resistance and endothelial dysfunction.
Endothelial dysfunction and insulin resistance are frequently comorbid states. Vasodilator actions of insulin are mediated by phosphatidylinositol 3-kinase (PI3K)-dependent signaling pathways that stimulate production of nitric oxide from vascular endothelium. This helps to couple metabolic and hemodynamic homeostasis under healthy conditions. In pathologic states, shared causal factors, including glucotoxicity, lipotoxicity, and inflammation selectively impair PI3K-dependent insulin signaling pathways that contribute to reciprocal relationships between insulin resistance and endothelial dysfunction. This article discusses the implications of pathway-selective insulin resistance in vascular endothelium, interactions between endothelial dysfunction and insulin resistance, and therapeutic interventions that may simultaneously improve both metabolic and cardiovascular physiology in insulin-resistant conditions.
Muniyappa
Ranganath
R
Diabetes Unit, National Center for Complementary and Alternative Medicine, National Institutes of Health, 10 Center Drive, 10-CRC, Room 4-1741, Bethesda, MD 20892-1632, USA.
Iantorno
Micaela
M
Quon
Michael J
MJ
D000818:Animals; D016207:Cytokines / Q000502:physiology; D019332:Endothelin-1 / Q000378:metabolism; D004730:Endothelium, Vascular / Q000502:physiology*; D005230:Fatty Acids, Nonesterified / Q000502:physiology; D006801:Humans; D007328:Insulin / Q000502:physiology; D007333:Insulin Resistance; D009569:Nitric Oxide / Q000502:physiology; D015398:Signal Transduction
D016207:Cytokines; D019332:Endothelin-1; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D009569:Nitric Oxide
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