Molecular and physiologic actions of insulin related to production of nitric oxide in vascular endothelium

被引:190
作者
Michelle A. Vincent
Monica Montagnani
Michael J. Quon
机构
[1] Laboratory of Clinical Investigation, NCCAM, National Institutes of Health, Bethesda, MD 20892-1632
关键词
Nitric Oxide; Insulin Receptor; Glucose Disposal; Capillary Recruitment; Limb Blood Flow;
D O I
10.1007/s11892-003-0018-9
中图分类号
学科分类号
摘要
Insulin has important vascular actions that regulate blood flow, in addition to its classical actions to coordinate glucose homeostasis. Insulin-stimulated production of nitric oxide in vascular endothelium results in capillary recruitment and vasodilation that diverts and increases blood flow to skeletal muscle and consequently increases glucose disposal. Thus, vascular actions of insulin may be essential for coupling hemodynamic and metabolic homeostasis. A complete biochemical signaling pathway linking the insulin receptor to activation of endothelial nitric oxide synthase in vascular endothelium has recently been elucidated. Moreover, the time course and dose response for capillary recruitment in response to physiologic concentrations of insulin parallels that of insulin-mediated glucose uptake in vivo. Taken together, these observations suggest a molecular mechanism that may help to explain how insulin resistance contributes to cardiovascular components of the metabolic syndrome and vascular complications of diabetes. Copyright © 2003 by Current Science Inc.
引用
收藏
页码:279 / 288
页数:9
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共 75 条
[1]  
Simionescu M., Gafencu A., Antohe F., Transcytosis of plasma macromolecules in endothelial cells: A cell biological survey, Microsc. Res. Tech., 57, pp. 269-288, (2002)
[2]  
Zeng G., Quon M.J., Insulin-stimulated production of nitric oxide is inhibited by wortmannin. Direct measurement in vascular endothelial cells, J. Clin. Invest., 98, pp. 894-898, (1996)
[3]  
Zeng G., Nystrom F.H., Ravichandran L.V., Et al., Roles for insulin receptor, PI3-kinase, and Akt in insulin-signaling pathways related to production of nitric oxide in human vascular endothelial cells, Circulation, 101, pp. 1539-1545, (2000)
[4]  
Montagnani M., Chen H., Barr V.A., Et al., Insulin-stimulated activation of eNOS is independent of Ca2+ but requires phosphorylation by Akt at Ser(1179), J. Biol. Chem., 276, pp. 30392-30398, (2001)
[5]  
Montagnani M., Ravichandran L.V., Chen H., Et al., Insulin receptor substrate-1 and phosphoinositide-dependent kinase-1 are required for insulin-stimulated production of nitric oxide in endothelial cells, Mol. Endocrinol., 16, pp. 1931-1942, (2002)
[6]  
Baron A.D., Hemodynamic actions of insulin, Am. J. Physiol., 267, (1994)
[7]  
Vincent M.A., Dawson D., Clark A.D., Et al., Skeletal muscle microvascular recruitment by physiological hyperinsulinemia precedes increases in total blood flow, Diabetes, 51, pp. 42-48, (2002)
[8]  
Vincent M.A., Barrett E.J., Insulin-induced capillary recruitment precedes changes in skeletal muscle glucose uptake, Diabetes, 51, SUPPL. 2, (2002)
[9]  
Vincent M.A., Clerk L.H., Barrett E., Skeletal muscle microvascular recruitment is more sensitive than femoral blood flow or glucose disposal, Diabetes, 52, SUPPL. 2, (2003)
[10]  
Vincent M.A., Lindner J.R., Barrett E.J., Et al., Inhibiting NOS blocks microvascular recruitment and blunts muscle glucose uptake in response to insulin, Am. J. Physiol., 285, (2003)