We have investigated whether angiotensin II (AII) is able to induce insulin receptor substrate 1 (IRS-1) phosphorylation and its association with phosphatidylinositol 3-kinase (PI 3-kinase) in the rat heart in vivo. The phosphorylation state of IRS-1 following infusion of insulin or AII via the vena cava was assessed after immunoprecipitation with an anti-peptide antibody to IRS-1 followed by immunoblotting with an anti-phosphotyrosine antibody and an anti-PI 3-kinase antibody. Densitometry indicated a 5.6 +/- 1.3-fold increase in IRS-1 phosphorylation after stimulation with AII and a 12.8 +/- 3.1-fold increase after insulin. The effect was maximal at an AII concentration of 10(-8) M and occurred 1 min after infusion. There was also a 6.1 +/- 1.2-fold increase in IRS-1-associated PI 3-kinase in response to AII. In the isolated perfused heart the result was similar, showing a direct effect of AII on this pathway. When the animals were pretreated for 1 h with DuP 753, a non-peptide AII-receptor 1 (AT1 receptor) antagonist, there was a marked reduction in the AII-induced tyrosine phosphorylation of IRS-1, suggesting that phosphorylation is initially mediated by the AT1 receptor. We conclude that AII stimulates tyrosine phosphorylation of IRS-1 and its association with PI 3-kinase. This pathway thus represents an additional signalling mechanism stimulated by AII in the rat heart in vivo.
Skip Nav Destination
Follow us on Twitter @Biochem_Journal
Article navigation
September 1995
-
Cover Image
Cover Image
- PDF Icon PDF LinkFront Matter
- PDF Icon PDF LinkTable of Contents
- PDF Icon PDF LinkAdvertising
Research Article|
September 15 1995
Angiotensin II induces tyrosine phosphorylation of insulin receptor substrate 1 and its association with phosphatidylinositol 3-kinase in rat heart
M J A Saad;
M J A Saad
1Laboratory of Cellular and Molecular Biology, Department of Internal Medicine, FCM, UNICAMP Campinas, SP, Brazil 13081-970
Search for other works by this author on:
L A Velloso;
L A Velloso
1Laboratory of Cellular and Molecular Biology, Department of Internal Medicine, FCM, UNICAMP Campinas, SP, Brazil 13081-970
Search for other works by this author on:
C R O Carvalho
C R O Carvalho
1Laboratory of Cellular and Molecular Biology, Department of Internal Medicine, FCM, UNICAMP Campinas, SP, Brazil 13081-970
Search for other works by this author on:
Publisher: Portland Press Ltd
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© 1995 The Biochemical Society, London
1995
Biochem J (1995) 310 (3): 741–744.
Citation
M J A Saad, L A Velloso, C R O Carvalho; Angiotensin II induces tyrosine phosphorylation of insulin receptor substrate 1 and its association with phosphatidylinositol 3-kinase in rat heart. Biochem J 15 September 1995; 310 (3): 741–744. doi: https://doi.org/10.1042/bj3100741
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Could not validate captcha. Please try again.
Biochemical Society Member Sign in
Sign InSign in via your Institution
Sign in via your InstitutionGet Access To This Article
Follow us on Twitter @Biochem_Journal
Open Access for all
We offer compliant routes for all authors from 2025. With library support, there will be no author nor reader charges in 5 journals. Check here |
![]() View past webinars > |