Angiotensin II Impairs the Insulin Signaling Pathway Promoting Production of Nitric Oxide by Inducing Phosphorylation of Insulin Receptor Substrate-1 on Ser 312 and Ser 616 in Human Umbilical Vein Endothelial Cells
- 14 May 2004
- journal article
- research article
- Published by Wolters Kluwer Health in Circulation Research
- Vol. 94 (9) , 1211-1218
- https://doi.org/10.1161/01.res.0000126501.34994.96
Abstract
It has been suggested that serine (Ser) phosphorylation of insulin receptor substrate-1 (IRS-1) decreases the ability of IRS-1 to be phosphorylated on tyrosine, thereby attenuating insulin signaling. There is evidence that angiotensin II (AII) may impair insulin signaling to the IRS-1/phosphatydilinositol 3-kinase (PI 3-kinase) pathway by enhancing Ser phosphorylation. Insulin stimulates NO production by a pathway involving IRS-1/PI3-kinase/Akt/endothelial NO synthase (eNOS). We addressed the question of whether AII affects insulin signaling involved in NO production in human umbilical vein endothelial cells and tested the hypothesis that the inhibitory effect of AII on insulin signaling was caused by increased site-specific Ser phosphorylation in IRS-1. Exposure of human umbilical vein endothelial cells to AII resulted in inhibition of insulin-stimulated production of NO. This event was associated with impaired IRS-1 phosphorylation at Tyr612 and Tyr632, two sites essential for engaging the p85 subunit o...Keywords
This publication has 22 references indexed in Scilit:
- Akt Is a Major Downstream Target of PI3-Kinase Involved in Angiotensin II–Induced ProliferationHypertension, 2003
- Insulin-Induced Akt Activation Is Inhibited by Angiotensin II in the Vasculature Through Protein Kinase C-αHypertension, 2003
- Insulin-Dependent Activation of Endothelial Nitric Oxide Synthase Is Impaired by O-Linked Glycosylation Modification of Signaling Proteins in Human Coronary Endothelial CellsCirculation, 2002
- Angiotensin II activates Akt/protein kinase B by an arachidonic acid/redox‐dependent pathway and independent of phosphoinositide 3‐kinaseThe FASEB Journal, 2001
- Tyr612 and Tyr632 in Human Insulin Receptor Substrate-1 Are Important for Full Activation of Insulin-Stimulated Phosphatidylinositol 3-Kinase Activity and Translocation of GLUT4 in Adipose Cells*Endocrinology, 2001
- Bradykinin-regulated Interactions of the Mitogen-activated Protein Kinase Pathway with the Endothelial Nitric-oxide SynthaseJournal of Biological Chemistry, 2000
- Characterization of selective resistance to insulin signaling in the vasculature of obese Zucker (fa/fa) ratsJournal of Clinical Investigation, 1999
- Angiotensin II inhibits insulin signaling in aortic smooth muscle cells at multiple levels. A potential role for serine phosphorylation in insulin/angiotensin II crosstalk.Journal of Clinical Investigation, 1997
- Protein Kinase C Modulation of Insulin Receptor Substrate-1 Tyrosine Phosphorylation Requires Serine 612Biochemistry, 1997
- IRS-1-Mediated Inhibition of Insulin Receptor Tyrosine Kinase Activity in TNF-α- and Obesity-Induced Insulin ResistanceScience, 1996