{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T17:09:29Z","timestamp":1791220169251,"version":"4.1.0"},"reference-count":0,"publisher":"National Academy of Sciences","issue":"22","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1996,10,29]]},"abstract":"<jats:p>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 phosphatidylinositol 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 role in the association of insulin resistance, hypertension, and cardiovascular disease.<\/jats:p>","DOI":"10.1073\/pnas.93.22.12490","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:34:16Z","timestamp":1027679656000},"page":"12490-12495","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":313,"title":["Cross-talk between the insulin and angiotensin signaling systems."],"prefix":"10.1073","volume":"93","author":[{"given":"L A","family":"Velloso","sequence":"first","affiliation":[{"name":"Laboratory of Cellular and Molecular Biology, University of Campinas-UNICAMP, Campinas, Brazil."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F","family":"Folli","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular and Molecular Biology, University of Campinas-UNICAMP, Campinas, Brazil."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"X J","family":"Sun","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular and Molecular Biology, University of Campinas-UNICAMP, Campinas, Brazil."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M F","family":"White","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular and Molecular Biology, University of Campinas-UNICAMP, Campinas, Brazil."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M J","family":"Saad","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular and Molecular Biology, University of Campinas-UNICAMP, Campinas, Brazil."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C R","family":"Kahn","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular and Molecular Biology, University of Campinas-UNICAMP, Campinas, Brazil."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[1996,10,29]]},"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.93.22.12490","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T15:00:50Z","timestamp":1649862050000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.93.22.12490"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1996,10,29]]},"references-count":0,"journal-issue":{"issue":"22","published-print":{"date-parts":[[1996,10,29]]}},"alternative-id":["10.1073\/pnas.93.22.12490"],"URL":"https:\/\/doi.org\/10.1073\/pnas.93.22.12490","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[1996,10,29]]},"assertion":[{"value":"1996-10-29","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}