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dc.contributor.CRUESPUniversidade Estadual de Campinaspt_BR
dc.typeArtigo de periódicopt_BR
dc.titlePhosphoinositide-specific inositol polyphosphate 5-phosphatase IV inhibits inositide trisphosphate accumulation in hypothalamus and regulates food intake and body weightpt_BR
dc.contributor.authorBertelli, DFpt_BR
dc.contributor.authorAraujo, EPpt_BR
dc.contributor.authorCesquini, Mpt_BR
dc.contributor.authorStoppa, GRpt_BR
dc.contributor.authorGasparotto-Contessotto, Mpt_BR
dc.contributor.authorToyama, MHpt_BR
dc.contributor.authorFelix, JVCpt_BR
dc.contributor.authorCarvalheira, JBpt_BR
dc.contributor.authorMichelini, LCpt_BR
dc.contributor.authorChiavegatto, Spt_BR
dc.contributor.authorBoschero, ACpt_BR
dc.contributor.authorSaad, MJApt_BR
dc.contributor.authorLopes-Cendes, Ipt_BR
dc.contributor.authorVelloso, LApt_BR
unicamp.author.emaillavelloso@fcm.unicamp.brpt_BR
unicamp.authorUniv Estadual Campinas, Dept Internal Med, BR-13083970 Campinas, SP, Brazil Univ Estadual Campinas, Dept Med Genet, BR-13083970 Campinas, SP, Brazil Univ Estadual Campinas, Dept Physiol & Biophys, BR-13083970 Campinas, SP, Brazil Univ Sao Paulo, Dept Physiol & Biophys, BR-05508900 Sao Paulo, Brazil Univ Sao Paulo, Inst Coracao, BR-05508900 Sao Paulo, Brazilpt_BR
dc.subject.wosInsulin-receptor Substrate-2pt_BR
dc.subject.wosCentral-nervous-systempt_BR
dc.subject.wosPhosphatidylinositol 3-kinasept_BR
dc.subject.wosChromatographic Analysispt_BR
dc.subject.wosSignaling Systemspt_BR
dc.subject.wosCell-functionpt_BR
dc.subject.wosBeta-cellspt_BR
dc.subject.wosCross-talkpt_BR
dc.subject.wosShip2pt_BR
dc.subject.wosObesitypt_BR
dc.description.abstractThe enzyme phosphatidylinositol 3-kinase (PI3-kinase) exerts an important role in the transduction of the anorexigenic and thermogenic signals delivered by insulin and leptin to first-order neurons of the arcuate nucleus in the hypothalamus. The termination of the intracellular signals generated by the activation of PI3-kinase depends on the coordinated activity of specific inositol phosphatases. Here we show that phosphoinositide-specific inositol polyphosphate 5-phosphatase IV (5ptase IV) is highly expressed in neurons of the arcuate and lateral nuclei of the hypothalamus. Upon intracerebro-ventricular (ICV) treatment with insulin, 5ptase IV undergoes a time-dependent tyrosine phosphorylation, which follows the same patterns of canonical insulin signaling through the insulin receptor, insulin receptor substrate-2, and PI3-kinase. To evaluate the participation of 5ptase IV in insulin action in hypothalamus, we used a phosphorthioate-modified antisense oligonucleotide specific for this enzyme. The treatment of rats with this oligonucleotide for 4 d reduced the hypothalamic expression of 5ptase IV by approximately 80%. This was accompanied by an approximately 70% reduction of insulin-induced tyrosine phosphorylation of 5ptase IV and an increase in basal accumulation of phosphorylated inositols in the hypothalamus. Finally, inhibition of hypothalamic 5ptase IV expression by the antisense approach resulted in reduced daily food intake and body weight loss. Thus, 5ptase IV is a powerful regulator of signaling through PI3-kinase in hypothalamus and may become an interesting target for therapeutics of obesity and related disorders.pt
dc.description.noteo TEXTO COMPLETO DESTE ARTIGO, ESTARÁ DISPONÍVEL À PARTIR DE AGOSTO DE 2015.pt
dc.relation.ispartofEndocrinologypt_BR
dc.relation.ispartofabbreviationEndocrinologypt_BR
dc.publisher.cityChevy Chasept_BR
dc.publisher.countryEUApt_BR
dc.publisherEndocrine Socpt_BR
dc.date.issued2006pt_BR
dc.date.monthofcirculationNOVpt_BR
dc.identifier.citationEndocrinology. Endocrine Soc, v. 147, n. 11, n. 5385, n. 5399, 2006.pt_BR
dc.language.isoenpt_BR
dc.description.volume147pt_BR
dc.description.issuenumber11pt_BR
dc.description.firstpage5385pt_BR
dc.description.lastpage5399pt_BR
dc.rightsembargopt_BR
dc.sourceWeb of Sciencept_BR
unicamp.cruespUSPpt_BR
dc.identifier.issn0013-7227pt_BR
dc.identifier.wosidWOS:000241324900045pt_BR
dc.identifier.doi10.1210/en.2006-0280pt_BR
dc.date.available2014-11-17T17:21:16Z
dc.date.available2015-11-26T17:40:50Z-
dc.date.accessioned2014-11-17T17:21:16Z
dc.date.accessioned2015-11-26T17:40:50Z-
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dc.description.provenanceMade available in DSpace on 2015-11-26T17:40:50Z (GMT). No. of bitstreams: 2 WOS000241324900045.pdf: 1296569 bytes, checksum: 705df3a02f2d1c294ed4ab3030a5dddc (MD5) WOS000241324900045.pdf.txt: 82159 bytes, checksum: d6880eb3efa87d9b57e11cd03f20078a (MD5) Previous issue date: 2006en
dc.identifier.urihttp://www.repositorio.unicamp.br/jspui/handle/REPOSIP/59527pt_BR
dc.identifier.urihttp://www.repositorio.unicamp.br/handle/REPOSIP/59527
dc.identifier.urihttp://repositorio.unicamp.br/jspui/handle/REPOSIP/59527-
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