S-nitrosation Of The Insulin Receptor, Insulin Receptor Substrate 1, And Protein Kinase B/akt: A Novel Mechanism Of Insulin Resistance.

dc.creatorCarvalho-Filho, Marco A
dc.creatorUeno, Mirian
dc.creatorHirabara, Sandro M
dc.creatorSeabra, Amedea B
dc.creatorCarvalheira, José B C
dc.creatorde Oliveira, Marcelo G
dc.creatorVelloso, Lício A
dc.creatorCuri, Rui
dc.creatorSaad, Mario J A
dc.date2005-Apr
dc.date2015-11-27T13:01:58Z
dc.date2015-11-27T13:01:58Z
dc.date.accessioned2018-03-29T01:00:35Z
dc.date.available2018-03-29T01:00:35Z
dc.identifierDiabetes. v. 54, n. 4, p. 959-67, 2005-Apr.
dc.identifier0012-1797
dc.identifier
dc.identifierhttp://www.ncbi.nlm.nih.gov/pubmed/15793233
dc.identifierhttp://repositorio.unicamp.br/jspui/handle/REPOSIP/196203
dc.identifier15793233
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1296436
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 (IRbeta) and protein kinase B/Akt (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 IRbeta/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.description959-67
dc.languageeng
dc.relationDiabetes
dc.relationDiabetes
dc.rightsfechado
dc.rights
dc.sourcePubMed
dc.subjectAnimals
dc.subjectGlutathione
dc.subjectInsulin
dc.subjectInsulin Receptor Substrate Proteins
dc.subjectInsulin Resistance
dc.subjectMale
dc.subjectMice
dc.subjectMice, Inbred Nod
dc.subjectMuscle, Skeletal
dc.subjectNitric Oxide
dc.subjectNitro Compounds
dc.subjectNitrosation
dc.subjectObesity
dc.subjectPhosphoproteins
dc.subjectProtein Processing, Post-translational
dc.subjectProtein-serine-threonine Kinases
dc.subjectProto-oncogene Proteins
dc.subjectProto-oncogene Proteins C-akt
dc.subjectRats
dc.subjectRats, Wistar
dc.subjectReceptor, Insulin
dc.subjectThiazolidinediones
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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