Please use this identifier to cite or link to this item: http://repositorio.unicamp.br/jspui/handle/REPOSIP/103455
Type: Artigo de periódico
Title: Targeted Disruption Of Inos Prevents Lps-induced S-nitrosation Of Irβ/irs-1 And Akt And Insulin Resistance In Muscle Of Mice
Author: Carvalho-Filho M.A.
Ueno M.
Carvalheira J.B.C.
Velloso L.A.
Saad M.J.A.
Abstract: We have previously demonstrated that the insulin resistance associated with inducible nitric oxide synthase (iNOS) induction in two different models of obesity, diet-induced obesity and the ob/ob mice, is mediated by S-nitrosation of proteins involved in insulin signal transduction: insulin receptor β-subunit (IRβ), insulin receptor substrate 1(IRS-1), and Akt. S-nitrosation of IRβ and Akt impairs their kinase activities, and S-nitrosation of IRS-1 reduces its tissue expression. In this study, we observed that LPS-induced insulin resistance in the muscle of wild-type mice, as demonstrated by reduced insulin-induced tyrosine phosphorylation of IRβ and IRS-1, reduced IRS-1 expression and reduced insulin-induced serine phosphorylation of Akt. This resistance occurred in parallel with enhanced iNOS expression, which was accompanied by S-nitrosation of IRβ/IRS-1 and Akt. In the muscle of iNOS-/- mice, we did not observe enhanced iNOS expression or any S-nitrosation of IRβ/IRS-1 and Akt after LPS treatment. Moreover, insulin resistance was not present. The preservation of insulin-induced tyrosine phosphorylation of IRβ and IRS-1, of IRS-1 protein expression, and of insulin-induced serine phosphorylation of Akt observed in LPS-treated iNOS-/- mice strongly suggests that the insulin resistance induced by LPS is iNOS mediated, probably through S-nitrosation of proteins of early steps of insulin signaling. Copyright © 2006 the American Physiological Society.
Editor: 
Rights: fechado
Identifier DOI: 10.1152/ajpendo.00422.2005
Address: http://www.scopus.com/inward/record.url?eid=2-s2.0-33748470543&partnerID=40&md5=3abc868a91e2b734bb3a8e82d189f79f
Date Issue: 2006
Appears in Collections:Unicamp - Artigos e Outros Documentos

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