Please use this identifier to cite or link to this item: http://repositorio.unicamp.br/jspui/handle/REPOSIP/80060
Type: Artigo de periódico
Title: Regulation of IRS-1/SHP2 interaction and AKT phosphorylation in animal models of insulin resistance
Author: Lima, MHM
Ueno, M
Thirone, ACP
Rocha, EM
Carvalho, CRO
Saad, MJA
Abstract: Insulin stimulates tyrosine kinase activity of its receptor, resulting in phosphorylation of its cytosolic substrate, insulin receptor substrate-1, which, in turn, associates with proteins containing SH2 domains, including phosphatidylinositol 3-kinase (PI 3-kinase) and the phosphotyrosine phosphatase SHP2. The regulation of these associations in situations of altered insulin receptor substrate-1 (IRS-1) phosphorylation was not yet investigated. In the present study, we investigated insulin-induced IRS-1/SHP2 and IRS-1/PI 3-kinase associations and the regulation of a downstream serine-kinase AKT/PKB in liver and muscle of three animal models of insulin resistance: STZ diabetes, epinephrine-treated rats, and aging, which have alterations in IRS-1 tyrosine phosphorylation in common. The results demonstrated that insulin-induced IRS-1/PI 3-kinase association has a close correlation with IRS-1 tyrosine phosphorylation levels, but insulin-induced IRS-1/SHP2 association showed a modulation that did not parallel IRS-1 phosphorylation, with a tissue-specific regulation in aging. The integration of the behavior of IRS-1/PI 3-kinase and with IRS-1/SHP2 associations may be important for insulin signaling downstream as AKT phosphorylation. In conclusion, the results of the present study demonstrated that insulin-induced IRS-1/SHP2 association can be regulated in insulin-sensitive tissues of animal models of insulin resistance and may have a role in the control of AKT phosphorylation, which may be implicated in the control of glucose metabolism.
Subject: insulin receptor substrate-1
phosphotyrosine phosphatase
signal transduction
insulin resistance
SHP2
Country: EUA
Editor: Humana Press Inc
Citation: Endocrine. Humana Press Inc, v. 18, n. 1, n. 1, n. 12, 2002.
Rights: fechado
Identifier DOI: 10.1385/ENDO:18:1:01
Date Issue: 2002
Appears in Collections:Unicamp - Artigos e Outros Documentos

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