Cross-talk between the insulin and angiotensin signaling systems

Lício A. Velloso, Franco Folli, Xiao J. Sun, Morris F. White, Mario J.A. Saad, C. Ronald Kahn

Research output: Contribution to journalArticlepeer-review

341 Scopus citations

Abstract

Angiotensin II (AII), acting via its G-protein linked receptor, is an important regulator of cardiac, vascular, and renal function. Following injection of AII into rats, we find that there is also a rapid tyrosine phosphorylation of the major insulin receptor substrates 1 and 2 (IRS-1 and IRS-2) in the heart. This phenomenon appears to involve JAK2 tyrosine kinase, which associates with the AT1 receptor and IRS-1/IRS-2 after AII stimulation. AII-induced phosphorylation leads to binding of pbosphatidylinositol 3- kinase (PI 3-kinase) to IRS-1 and IRS-2; however, in contrast to other ligands, AII injection results in an acute inhibition of both basal and insulin-stimulated PI 3-kinase activity. The latter occurs without any reduction in insulin receptor or IRS phosphorylation or in the interaction of the p85 and p110 subunits of PI 3-kinase with each other or with IRS-1/IRS- 2. These effects of AII are inhibited by AT1 receptor antagonists. Thus, there is direct cross-talk between insulin and AII signaling pathways at the level of both tyrosine phosphorylation and PI 3-kinase activation. These interactions may play an important rule in the association of insulin resistance, hypertension, and cardiovascular disease.

Original languageEnglish (US)
Pages (from-to)12490-12495
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume93
Issue number22
DOIs
StatePublished - Oct 29 1996
Externally publishedYes

ASJC Scopus subject areas

  • General

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