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Type: Artigo de periódico
Title: The Cross-talk Between Angiotensin And Insulin Differentially Affects Phosphatidylinositol 3-kinase- And Mitogen-activated Protein Kinase-mediated Signaling In Rat Heart: Implications For Insulin Resistance.
Author: Carvalheira, José B C
Calegari, Vivian C
Zecchin, Henrique G
Nadruz, Wilson
Guimarães, Regina B
Ribeiro, Eliane B
Franchini, Kleber G
Velloso, Lício A
Saad, Mario J A
Abstract: Insulin and angiotensin II (AngII) may act through overlapping intracellular pathways to promote cardiac myocyte growth. In this report insulin and AngII signaling, through the phosphatidylinositol 3-kinase (PI 3-kinase) and MAPK pathways, were compared in cardiac tissues of control and obese Zucker rats. AngII induced Janus kinase 2 tyrosine phosphorylation and coimmunoprecipitation with insulin receptor substrate 1 (IRS-1) and IRS-2 as well as an increase in tyrosine phosphorylation of IRS and its association with growth factor receptor-binding protein 2. Simultaneous treatment with both hormones led to marked increases in the associations of IRS-1 and -2 with growth factor receptor-binding protein 2 and in the dual phosphorylation of ERK1/2 compared with the administration of AngII or insulin alone. In contrast, an acute inhibition of both basal and insulin-stimulated PI 3-kinase activity was induced by both hormones. Insulin stimulated the phosphorylation of MAPK equally in lean and obese rats. Conversely, insulin-induced phosphorylation of Akt in heart was decreased in obese rats. Pretreatment with losartan did not change insulin-induced activation of ERK1/2 and attenuated the reduction of Akt phosphorylation in the heart of obese rats. Thus, the imbalance between PI 3-kinase-Akt and MAPK signaling pathways in the heart may play a role in the development of cardiovascular abnormalities observed in insulin-resistant states, such as in obese Zucker rats.
Subject: Adaptor Proteins, Signal Transducing
Angiotensin Ii
Grb2 Adaptor Protein
Hypoglycemic Agents
Insulin Resistance
Janus Kinase 2
Map Kinase Signaling System
Mitogen-activated Protein Kinase 1
Mitogen-activated Protein Kinase 3
Mitogen-activated Protein Kinases
Phosphatidylinositol 3-kinases
Protein-serine-threonine Kinases
Protein-tyrosine Kinases
Proto-oncogene Proteins
Proto-oncogene Proteins C-akt
Rats, Wistar
Rats, Zucker
Receptor Cross-talk
Vasoconstrictor Agents
Citation: Endocrinology. v. 144, n. 12, p. 5604-14, 2003-Dec.
Rights: fechado
Identifier DOI: 10.1210/en.2003-0788
Date Issue: 2003
Appears in Collections:Unicamp - Artigos e Outros Documentos

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