Please use this identifier to cite or link to this item: http://repositorio.unicamp.br/jspui/handle/REPOSIP/196741
Type: Artigo de periódico
Title: Targeted Disruption Of Inos Prevents Lps-induced S-nitrosation Of Irbeta/irs-1 And Akt And Insulin Resistance In Muscle Of Mice.
Author: Carvalho-Filho, Marco A
Ueno, Mirian
Carvalheira, José B C
Velloso, Lício A
Saad, Mario 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 beta-subunit (IRbeta), insulin receptor substrate 1(IRS-1), and Akt. S-nitrosation of IRbeta 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 IRbeta 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 IRbeta/IRS-1 and Akt. In the muscle of iNOS(-/-) mice, we did not observe enhanced iNOS expression or any S-nitrosation of IRbeta/IRS-1 and Akt after LPS treatment. Moreover, insulin resistance was not present. The preservation of insulin-induced tyrosine phosphorylation of IRbeta 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.
Subject: Adipose Tissue
Animals
Blood Glucose
Insulin
Insulin Receptor Substrate Proteins
Insulin Resistance
Lipopolysaccharides
Liver
Mice
Mice, Inbred Balb C
Mice, Knockout
Muscle, Skeletal
Nitric Oxide Synthase Type Ii
Nitrosation
Phosphoproteins
Phosphorylation
Protein Processing, Post-translational
Proto-oncogene Proteins C-akt
Receptor, Insulin
Rights: fechado
Identifier DOI: 10.1152/ajpendo.00422.2005
Address: http://www.ncbi.nlm.nih.gov/pubmed/16638822
Date Issue: 2006
Appears in Collections:Artigos e Materiais de Revistas Científicas - Unicamp

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