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dc.contributor.CRUESPUNIVERSIDADE DE ESTADUAL DE CAMPINASpt_BR
dc.typeArtigo de periódicopt_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 Bladder.pt_BR
dc.contributor.authorLeiria, Luiz Opt_BR
dc.contributor.authorSollon, Carolinapt_BR
dc.contributor.authorBáu, Fernando Rpt_BR
dc.contributor.authorMónica, Fabíola Zpt_BR
dc.contributor.authorD'Ancona, Carlos Lpt_BR
dc.contributor.authorDe Nucci, Gilbertopt_BR
dc.contributor.authorGrant, Andrew Dpt_BR
dc.contributor.authorAnhê, Gabriel Fpt_BR
dc.contributor.authorAntunes, Edsonpt_BR
unicamp.authorLuiz O Leiria, Department of Pharmacology and Division of Urology, Faculty of Medical Sciences, State University of Campinas, UNICAMP, Campinas São Paulo, Brazil.pt_BR
unicamp.author.externalCarolina Sollon,pt
unicamp.author.externalFernando R Báu,pt
unicamp.author.externalFabíola Z Mónica,pt
unicamp.author.externalCarlos L D'Ancona,pt
unicamp.author.externalGilberto De Nucci,pt
unicamp.author.externalAndrew D Grant,pt
unicamp.author.externalGabriel F Anhê,pt
unicamp.author.externalEdson Antunes,pt
dc.subjectAdolescentpt_BR
dc.subjectAdultpt_BR
dc.subjectAnimalspt_BR
dc.subjectDiet, High-fatpt_BR
dc.subjectHumanspt_BR
dc.subjectInsulinpt_BR
dc.subjectInsulin Resistancept_BR
dc.subjectMalept_BR
dc.subjectMicept_BR
dc.subjectMice, Inbred C57blpt_BR
dc.subjectMiddle Agedpt_BR
dc.subjectMucous Membranept_BR
dc.subjectMuscle Relaxationpt_BR
dc.subjectNitric Oxide Synthase Type Iiipt_BR
dc.subjectObesitypt_BR
dc.subjectPhosphatidylinositol 3-kinasespt_BR
dc.subjectProto-oncogene Proteins C-aktpt_BR
dc.subjectUnfolded Protein Responsept_BR
dc.subjectUrinary Bladderpt_BR
dc.subjectUrinary Bladder, Overactivept_BR
dc.subjectYoung Adultpt_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. Concentration-response 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 (1-100 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 mice.en
dc.relation.ispartofThe Journal Of Physiologypt_BR
dc.relation.ispartofabbreviationJ. Physiol. (Lond.)pt_BR
dc.date.issued2013-Maypt_BR
dc.identifier.citationThe Journal Of Physiology. v. 591, n. Pt 9, p. 2259-73, 2013-May.pt_BR
dc.language.isoengpt_BR
dc.description.volume591pt_BR
dc.description.firstpage2259-73pt_BR
dc.rightsfechadopt_BR
dc.sourcePubMedpt_BR
dc.identifier.issn1469-7793pt_BR
dc.identifier.doi10.1113/jphysiol.2013.251843pt_BR
dc.identifier.urlhttp://www.ncbi.nlm.nih.gov/pubmed/23478138pt_BR
dc.date.available2015-11-27T13:31:28Z-
dc.date.accessioned2015-11-27T13:31:28Z-
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dc.identifier.urihttp://repositorio.unicamp.br/jspui/handle/REPOSIP/200524-
dc.identifier.idPubmed23478138pt_BR
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