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dc.contributor.CRUESPUniversidade Estadual de Campinaspt_BR
dc.typeArtigo de periódicopt_BR
dc.titleInhibition of UCP2 expression reverses diet-induced diabetes mellitus by effects on both insulin secretion and actionpt_BR
dc.contributor.authorDe Souza, CTpt_BR
dc.contributor.authorAraujo, EPpt_BR
dc.contributor.authorStoppiglia, LFpt_BR
dc.contributor.authorPauli, JRpt_BR
dc.contributor.authorRopelle, Ept_BR
dc.contributor.authorRocco, SApt_BR
dc.contributor.authorMarin, RMpt_BR
dc.contributor.authorFranchini, KGpt_BR
dc.contributor.authorCarvalheira, JBpt_BR
dc.contributor.authorSaad, MJpt_BR
dc.contributor.authorBoschero, ACpt_BR
dc.contributor.authorCarneiro, EMpt_BR
dc.contributor.authorVelloso, LApt_BR
unicamp.author.emaillavelloso@fcm.unicamp.brpt_BR
unicamp.authorUniv Estadual Campinas, Dept Internal Med, Campinas, SP, Brazil Univ Estadual Campinas, Dept Phys & Biophys, Campinas, SP, Brazilpt_BR
dc.subjectshort-term inhibition of UCP2pt_BR
dc.subjectantisense oligonucleotidept_BR
dc.subjectATP synthasept_BR
dc.subjectanti-UCP2 antibodypt_BR
dc.subject.wosBeta-cell Dysfunctionpt_BR
dc.subject.wosUncoupling Proteins Ucp2pt_BR
dc.subject.wosPancreatic-isletspt_BR
dc.subject.wosReceptor Substrate-1pt_BR
dc.subject.wosOxidative Stresspt_BR
dc.subject.wosObesitypt_BR
dc.subject.wosResistancept_BR
dc.subject.wosMicept_BR
dc.subject.wosOverexpressionpt_BR
dc.subject.wosHyperinsulinemiapt_BR
dc.description.abstractRecent characterization of the ability of uncoupling protein 2 (UCP2) to reduce ATP production and inhibit insulin secretion by pancreatic beta-cells has placed this mitochondrial protein as a candidate target for therapeutics in diabetes mellitus. In the present study we evaluate the effects of short-term treatment of two animal models of type 2 diabetes mellitus with an antisense oligonucleotide to UCP2. In both models, Swiss mice ( made obese and diabetic by a hyperlipidic diet) and ob/ob mice, the treatment resulted in a significant improvement in the hyperglycemic syndrome. This effect was due not only to an improvement of insulin secretion, but also to improved peripheral insulin action. In isolated pancreatic islets, the partial inhibition of UCP2 increased ATP content, followed by increased glucose-stimulated insulin secretion. This was not accompanied by increased expression of enzymes involved in protection against oxidative stress. The evaluation of insulin action in peripheral tissues revealed that the inhibition of UCP2 expression significantly improved insulin signal transduction in adipose tissue. In conclusion, short-term inhibition of UCP2 expression ameliorates the hyperglycemic syndrome in two distinct animal models of obesity and diabetes. Metabolic improvement is due to a combined effect on insulin-producing pancreatic islets and in at least one peripheral tissue that acts as a target for insulin.pt
dc.relation.ispartofFaseb Journalpt_BR
dc.relation.ispartofabbreviationFaseb J.pt_BR
dc.publisher.cityBethesdapt_BR
dc.publisher.countryEUApt_BR
dc.publisherFederation Amer Soc Exp Biolpt_BR
dc.date.issued2007pt_BR
dc.date.monthofcirculationAPRpt_BR
dc.identifier.citationFaseb Journal. Federation Amer Soc Exp Biol, v. 21, n. 4, n. 1153, n. 1163, 2007.pt_BR
dc.language.isoenpt_BR
dc.description.volume21pt_BR
dc.description.issuenumber4pt_BR
dc.description.firstpage1153pt_BR
dc.description.lastpage1163pt_BR
dc.rightsfechadopt_BR
dc.sourceWeb of Sciencept_BR
dc.identifier.issn0892-6638pt_BR
dc.identifier.wosidWOS:000245650400020pt_BR
dc.identifier.doi10.1096/fj.06-7148compt_BR
dc.date.available2014-11-18T07:16:19Z
dc.date.available2015-11-26T16:52:24Z-
dc.date.accessioned2014-11-18T07:16:19Z
dc.date.accessioned2015-11-26T16:52:24Z-
dc.description.provenanceMade available in DSpace on 2014-11-18T07:16:19Z (GMT). No. of bitstreams: 1 WOS000245650400020.pdf: 564953 bytes, checksum: 6d4b8d9a52095b8b9ce0b548a032012d (MD5) Previous issue date: 2007en
dc.description.provenanceMade available in DSpace on 2015-11-26T16:52:24Z (GMT). No. of bitstreams: 2 WOS000245650400020.pdf: 564953 bytes, checksum: 6d4b8d9a52095b8b9ce0b548a032012d (MD5) WOS000245650400020.pdf.txt: 52002 bytes, checksum: 0d6ec7ca2acb07cf19571738946195db (MD5) Previous issue date: 2007en
dc.identifier.urihttp://www.repositorio.unicamp.br/jspui/handle/REPOSIP/80654pt_BR
dc.identifier.urihttp://www.repositorio.unicamp.br/handle/REPOSIP/80654
dc.identifier.urihttp://repositorio.unicamp.br/jspui/handle/REPOSIP/80654-
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