Cross-talk between insulin and angiotensin signaling

F. Folli, L. A. Velloso, Mja Saad, C. R. Kahn

Research output: Contribution to journalArticlepeer-review


Angiotensin II (All), acting via its G-protein linked receptor, is an important regulator of cardiac, vascular, and renal function. Following injection of physiologic concentrations of All in rats, there is rapid 3- to 4-fold stimulation of tyrosyl phosphorylation of the major insulin receptor substrates IRS-I and IRS-2, followed by association of these substrates with the p85 subunit of PI 3-kinase in the heart. Phosphorylation of IRS-1 and 2 appears to involve cytoplasmic JAK2 tyrosine kinase which complexes with IRS-l/lRS-2 after All, as well as insulin, stimulation. As in other tissues, insulin stimulation results in a 8- to 30-fold increase in IRS-l and lRS-2associated PI-3 kinase activity. Surprisingly, however. All treatment results in a dose dependent inhibition of basal PI 3-kinase activity and inhibits insulin-stimulated IRS-I and IRS-2-associated PI 3-kinase activity by 75-80%. This ability of All to inhibit PI 3kinase activity occurs without any effect on insulin stimulation of receptor or 1RS tyrosyl phosphorylation, and with no reduction in the binding of p85 to 1RS or the binding of the pi 10 catalytic subunit of PI 3-K to the p85 regulatory subunit. Infusion of a pcptide blocker of the ATI receptor completely prevents All stimulation of IRS-l phosphorylation and the inhibitory effect of All on insulin-stimulated PI 3-kinase activity. Thus, All, acting through the ATI receptor, stimulates 1RS-1/2 tyrosine phosphorylation, but inhibits PI 3-kinase activity. This novel intracellular interaction between G-protein coupled and tyrosine kinase receptors may play an important role in the insulin resistance of hypertension and the association of these conditions with cardiovascular diseases.

Original languageEnglish (US)
Pages (from-to)271a
JournalJournal of Investigative Medicine
Issue number3
StatePublished - Jan 1 1996

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


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