S-nitrosation of the insulin receptor, insulin receptor substrate 1, and protein kinase B/Akt - A novel mechanism of insulin resistance

dc.creatorCarvalho, MA
dc.creatorUeno, M
dc.creatorHirabara, SM
dc.creatorSeabra, AB
dc.creatorCarvalheira, JBC
dc.creatorde Oliveira, MG
dc.creatorVelloso, LA
dc.creatorCuri, R
dc.creatorSaad, MJA
dc.date2005
dc.dateAPR
dc.date2014-11-20T04:10:35Z
dc.date2015-11-26T16:05:21Z
dc.date2014-11-20T04:10:35Z
dc.date2015-11-26T16:05:21Z
dc.date.accessioned2018-03-28T22:54:20Z
dc.date.available2018-03-28T22:54:20Z
dc.identifierDiabetes. Amer Diabetes Assoc, v. 54, n. 4, n. 959, n. 967, 2005.
dc.identifier0012-1797
dc.identifierWOS:000228094300006
dc.identifier10.2337/diabetes.54.4.959
dc.identifierhttp://www.repositorio.unicamp.br/jspui/handle/REPOSIP/71698
dc.identifierhttp://www.repositorio.unicamp.br/handle/REPOSIP/71698
dc.identifierhttp://repositorio.unicamp.br/jspui/handle/REPOSIP/71698
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1265680
dc.descriptionEvidence demonstrates that exogenous nitric oxide (NO) and the NO produced by inducible nitric oxide synthase (iNOS) can induce insulin resistance in muscle. Here, we investigated whether this insulin resistance could be mediated by S-nitrosation of proteins involved in early steps of the insulin signal transduction pathway. Exogenous NO donated by S-nitrosoglutathione (GSNO) induced in vitro and in vivo S-nitrosation of the insulin receptor beta subunit (IR beta) and protein kinase B/Alkt (Akt) and reduced their kinase activity in muscle. Insulin receptor substrate (IRS)-1 was also rapidly S-nitrosated, and its expression was reduced after chronic GSNO treatment. In two distinct models of insulin resistance associated with enhanced iNOS expression-diet-induced obesity and the ob/ob diabetic mice-we observed enhanced S-nitrosation of IR beta/IRS-1 and Akt in muscle. Reversal of S-nitrosation of these proteins by reducing iNOS expression yielded an improvement in insulin action in both animal models. Thus, S-nitrosation of proteins involved in insulin signal transduction is a novel molecular mechanism of iNOS-induced insulin resistance.
dc.description54
dc.description4
dc.description959
dc.description967
dc.languageen
dc.publisherAmer Diabetes Assoc
dc.publisherAlexandria
dc.publisherEUA
dc.relationDiabetes
dc.relationDiabetes
dc.rightsfechado
dc.sourceWeb of Science
dc.subjectNitric-oxide Synthase
dc.subjectNecrosis-factor-alpha
dc.subjectSkeletal-muscle
dc.subjectTyrosine Phosphorylation
dc.subjectAdipose-tissue
dc.subjectEnergy-expenditure
dc.subjectAnimal-models
dc.subjectHuman Obesity
dc.subjectNitrosylation
dc.subjectExpression
dc.titleS-nitrosation of the insulin receptor, insulin receptor substrate 1, and protein kinase B/Akt - A novel mechanism of insulin resistance
dc.typeArtículos de revistas


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