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Type: Artigo de periódico
Title: Targeted disruption of iNOS prevents LPS-induced S-nitrosation of IR beta/IRS-1 and Akt and insulin resistance in muscle of mice
Author: Carvalho-Filho, MA
Ueno, M
Carvalheira, J'BC
Velloso, LA
Saad, MJA
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 (IR beta), insulin receptor substrate 1(IRS-1), and Akt. S-nitrosation of IR beta 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 wildtype mice, as demonstrated by reduced insulin-induced tyrosine phosphorylation of IR beta 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 IR beta/IRS-1 and Akt. In the muscle of iNOS(-/-) mice, we did not observe enhanced iNOS expression or any S-nitrosation of IR beta/IRS-1 and Akt after LPS treatment. Moreover, insulin resistance was not present. The preservation of insulin-induced tyrosine phosphorylation of IR beta 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: inducible nitric oxide synthase
insulin receptor beta-subunit
insulin receptor substrate-1
Country: EUA
Editor: Amer Physiological Soc
Citation: American Journal Of Physiology-endocrinology And Metabolism. Amer Physiological Soc, v. 291, n. 3, n. E476, n. E482, 2006.
Rights: embargo
Identifier DOI: 10.1152/ajpendo.00422.2005
Date Issue: 2006
Appears in Collections:Unicamp - Artigos e Outros Documentos

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