Please use this identifier to cite or link to this item: http://repositorio.unicamp.br/jspui/handle/REPOSIP/60300
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dc.contributor.CRUESPUNIVERSIDADE ESTADUAL DE CAMPINASpt_BR
dc.contributor.authorunicampSilva, Carolina Solon dapt_BR
dc.contributor.authorunicampD'Ancona, Carlos Arturo Levipt_BR
dc.contributor.authorunicampLeiria, Luiz Osóriopt_BR
dc.contributor.authorunicampMónica, Fabíola Zakia Tauficpt_BR
dc.contributor.authorunicampAntunes, Edsonpt_BR
dc.contributor.authorunicampDe Nucci, Gilbertopt_BR
dc.contributor.authorunicampAnhê, Gabriel Foratopt_BR
dc.typeArtigopt_BR
dc.titleInsulin relaxes bladder via PI3K/AKT/eNOS pathway activation in mucosa: unfolded protein response-dependent insulin resistance as a cause of obesity-associated overactive bladderpt_BR
dc.contributor.authorBau, F.R.pt_BR
dc.contributor.authorSollon, C.pt_BR
dc.contributor.authorD'Ancona, C.L.pt_BR
dc.contributor.authorLeiria, L.O.pt_BR
dc.contributor.authorMonica, F.Z.pt_BR
dc.contributor.authorAntunes, E.pt_BR
dc.contributor.authorDe Nucci, G.pt_BR
dc.contributor.authorAnhe, G.F.pt_BR
dc.contributor.authorGrant, A.D.pt_BR
dc.subjectResistência à insulinapt_BR
dc.subjectOxido nítrico sintase tipo IIIpt_BR
dc.subjectDieta hiperlipídicapt_BR
dc.subject.otherlanguageDiet, high-fatpt_BR
dc.subject.otherlanguageInsulin resistancept_BR
dc.subject.otherlanguageNitric oxide synthase type IIIpt_BR
dc.description.abstractWe aimed to investigate the role of insulin in the bladder and its relevance for the development of overactive bladder (OAB) in insulin-resistant obese mice. Bladders from male individuals who were involved in multiple organ donations were used. C57BL6/J mice were fed with a high-fat diet for 10 weeks to induce insulin-resistant obesity. Concentrationresponse curves to insulin were performed in human and mouse isolated mucosa-intact and mucosa-denuded bladders. Cystometric study was performed in terminally anaesthetized mice. Western blot was performed in bladders to detect phosphorylated endothelial NO synthase (eNOS) (Ser1177) and the phosphorylated protein kinase AKT (Ser473), as well as the unfolded protein response (UPR) markers TRIB3, CHOP and ATF4. Insulin (1100 nm) produced concentration-dependent mouse and human bladder relaxations that were markedly reduced by mucosal removal or inhibition of the PI3K/AKT/eNOS pathway. In mouse bladders, insulin produced a 3.0-fold increase in cGMP levels (P < 0.05) that was prevented by PI3K/AKT/eNOS pathway inhibition. Phosphoinositide 3-kinase (PI3K) inhibition abolished insulin-induced phosphorylation of AKT and eNOS in bladder mucosa. Obese mice showed greater voiding frequency and non-voiding contractions, indicating overactive detrusor smooth muscle. Insulin failed to relax the bladder or to increase cGMP in the obese group. Insulin-stimulated AKT and eNOS phosphorylation in mucosa was also impaired in obese mice. The UPR markers TRIB3, CHOP and ATF4 were increased in the mucosa of obese mice. The UPR inhibitor 4-phenyl butyric acid normalized all the functional and molecular parameters in obese mice. Our data show that insulin relaxes human and mouse bladder via activation of the PI3K/AKT/eNOS pathway in the bladder mucosa. Endoplasmic reticulum stress-dependent insulin resistance in bladder contributes to OAB in obese micept
dc.description.eventWiley-Blackwellpt_BR
dc.relation.ispartofJournal of physiologypt_BR
dc.relation.ispartofabbreviationJ. physiol.pt_BR
dc.publisher.cityChichesterpt_BR
dc.publisher.countryReino Unidopt_BR
dc.publisherWileypt_BR
dc.date.issued2013pt_BR
dc.date.monthofcirculationMaypt_BR
dc.identifier.citationJournal Of Physiology-london. Wiley-blackwell, v. 591, n. 9, n. 2259, n. 2273, 2013.pt_BR
dc.language.isoengpt_BR
dc.description.volume591pt_BR
dc.description.issuenumber9pt_BR
dc.description.firstpage2259pt_BR
dc.description.lastpage2273pt_BR
dc.rightsfechadopt_BR
dc.sourcePUBMEDpt_BR
dc.identifier.issn0022-3751pt_BR
dc.identifier.eissn1469-7793pt_BR
dc.identifier.doi10.1113/jphysiol.2013.251843pt_BR
dc.identifier.urlhttps://physoc.onlinelibrary.wiley.com/doi/full/10.1113/jphysiol.2013.251843pt_BR
dc.description.sponsorshipFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESPpt_BR
dc.description.sponsorship1FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOpt_BR
dc.description.sponsordocumentnumbersem informaçãopt_BR
dc.date.available2014-07-30T14:33:45Z
dc.date.available2015-11-26T16:35:01Z-
dc.date.accessioned2014-07-30T14:33:45Z
dc.date.accessioned2015-11-26T16:35:01Z-
dc.description.provenanceMade available in DSpace on 2014-07-30T14:33:45Z (GMT). No. of bitstreams: 0 Previous issue date: 2013en
dc.description.provenanceMade available in DSpace on 2015-11-26T16:35:01Z (GMT). No. of bitstreams: 0 Previous issue date: 2013en
dc.identifier.urihttp://www.repositorio.unicamp.br/jspui/handle/REPOSIP/60300
dc.identifier.urihttp://repositorio.unicamp.br/jspui/handle/REPOSIP/60300-
dc.contributor.departmentsem informaçãopt_BR
dc.contributor.departmentDepartamento de Cirurgiapt_BR
dc.contributor.departmentsem informaçãopt_BR
dc.contributor.departmentDepartamento de Farmacologiapt_BR
dc.contributor.departmentDepartamento de Farmacologiapt_BR
dc.contributor.departmentDepartamento de Farmacologiapt_BR
dc.contributor.departmentDepartamento de Farmacologiapt_BR
dc.contributor.unidadeFaculdade de Ciências Médicaspt_BR
dc.identifier.source23478138-
dc.creator.orcidsem informaçãopt_BR
dc.creator.orcid0000-0002-5821-0292pt_BR
dc.creator.orcid0000-0001-9443-718Xpt_BR
dc.creator.orcid0000-0002-8449-6677pt_BR
dc.creator.orcid0000-0003-2201-8247pt_BR
dc.creator.orcid0000-0002-4346-7941pt_BR
dc.creator.orcidsem informaçãopt_BR
dc.type.formArtigo originalpt_BR
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