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dc.contributor.CRUESPUNIVERSIDADE DE ESTADUAL DE CAMPINASpt_BR
dc.typeArtigo de periódicopt_BR
dc.titleShort-term Inhibition Of Peroxisome Proliferator-activated Receptor-gamma Coactivator-1alpha Expression Reverses Diet-induced Diabetes Mellitus And Hepatic Steatosis In Mice.pt_BR
dc.contributor.authorDe Souza, C Tpt_BR
dc.contributor.authorAraújo, E Ppt_BR
dc.contributor.authorPrada, P Opt_BR
dc.contributor.authorSaad, M J Apt_BR
dc.contributor.authorBoschero, A Cpt_BR
dc.contributor.authorVelloso, L Apt_BR
unicamp.authorC T De Souza, Department of Internal Medicine, Faculty of Medical Sciences (FCM), State University of Campinas (UNICAMP), Campinas, São Paulo, 13083-970, Brazil.pt_BR
unicamp.author.externalE P Araújo,pt
unicamp.author.externalP O Prada,pt
unicamp.author.externalM J A Saad,pt
unicamp.author.externalA C Boschero,pt
unicamp.author.externalL A Velloso,pt
dc.subjectAdipose Tissuept_BR
dc.subjectAnimalspt_BR
dc.subjectBlood Glucosept_BR
dc.subjectDiabetes Mellituspt_BR
dc.subjectDietpt_BR
dc.subjectFatty Liverpt_BR
dc.subjectGene Expression Regulation, Enzymologicpt_BR
dc.subjectInsulinpt_BR
dc.subjectMicept_BR
dc.subjectMice, Inbred Cbapt_BR
dc.subjectSignal Transductionpt_BR
dc.subjectTrans-activatorspt_BR
dc.subjectTranscription Factorspt_BR
dc.description.abstractThe coactivator of nuclear receptors, peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha) has been implicated in a series of events that contribute to the control of glucose metabolism. We have recently reported the use of a PGC-1alpha antisense oligonucleotide (PGC-1alphaAS) that inhibits up to 60% of PGC-1alpha expression in pancreatic islets, leading to increased insulin secretion. This oligonucleotide was used in this study to try to ameliorate diet-induced type 2 diabetes in a genetically predisposed mouse strain (Swiss mice). Glucose and insulin tolerance tests, euglycaemic-hyperinsulinaemic clamp, immunoprecipitation assays, immunoblotting assays and immunohistochemistry were used in this investigation. Swiss mice became obese and overtly diabetic after 8 weeks of feeding with chow containing 24% saturated fat. One daily dose (1.0 nmol) of PGC-1alphaAS significantly reduced glucose and increased insulin blood levels without affecting food intake and body weight. These effects were accompanied by a reduced area under the glucose curve during an intraperitoneal glucose tolerance test, an increased constant of glucose decay (K(itt)) during an insulin tolerance test, and an increased glucose consumption rate during a euglycaemic-hyperinsulinaemic clamp. Moreover, mice treated with PGC-1alphaAS presented an outstanding reduction of macroscopic and microscopic features of hepatic steatosis. These effects were accompanied by reduced expression or function of a series of proteins involved in lipogenesis. PGC-1alpha is an attractive target for pharmacological therapeutics in type 2 diabetes mellitus and diet-induced hepatic steatosis.en
dc.relation.ispartofDiabetologiapt_BR
dc.relation.ispartofabbreviationDiabetologiapt_BR
dc.date.issued2005-Seppt_BR
dc.identifier.citationDiabetologia. v. 48, n. 9, p. 1860-71, 2005-Sep.pt_BR
dc.language.isoengpt_BR
dc.description.volume48pt_BR
dc.description.firstpage1860-71pt_BR
dc.rightsfechadopt_BR
dc.rights.holderpt_BR
dc.sourcePubMedpt_BR
dc.identifier.issn0012-186Xpt_BR
dc.identifier.doi10.1007/s00125-005-1866-4pt_BR
dc.identifier.urlhttp://www.ncbi.nlm.nih.gov/pubmed/16025253pt_BR
dc.date.available2015-11-27T13:02:16Z-
dc.date.accessioned2015-11-27T13:02:16Z-
dc.description.provenanceMade available in DSpace on 2015-11-27T13:02:16Z (GMT). No. of bitstreams: 1 pmed_16025253.pdf: 401609 bytes, checksum: ba2d29158eeb45adae170ae10db2f538 (MD5) Previous issue date: 2005en
dc.identifier.urihttp://repositorio.unicamp.br/jspui/handle/REPOSIP/196342-
dc.identifier.idPubmed16025253pt_BR
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