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dc.contributor.authorWang, Zongweien_US
dc.contributor.authorCheng, Zhiyongen_US
dc.contributor.authorCristofaro, Vivianen_US
dc.contributor.authorLi, Jijunen_US
dc.contributor.authorXiao, Xingyuanen_US
dc.contributor.authorGomez, Pabloen_US
dc.contributor.authorGe, Rongbinen_US
dc.contributor.authorGong, Edwarden_US
dc.contributor.authorStrle, Klemenen_US
dc.contributor.authorSullivan, Maryrose P.en_US
dc.contributor.authorAdam, Rosalyn M.en_US
dc.contributor.authorWhite, Morris F.en_US
dc.contributor.authorOlumi, Aria F.en_US
dc.date.accessioned2014-03-01T02:25:21Z
dc.date.issued2012en_US
dc.identifier.citationWang, Z., Z. Cheng, V. Cristofaro, J. Li, X. Xiao, P. Gomez, R. Ge, et al. 2012. “Inhibition of TNF-α Improves the Bladder Dysfunction That Is Associated With Type 2 Diabetes.” Diabetes 61 (8): 2134-2145. doi:10.2337/db11-1763. http://dx.doi.org/10.2337/db11-1763.en
dc.identifier.issn0012-1797en
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:11855888
dc.description.abstractDiabetic bladder dysfunction (DBD) is common and affects 80% of diabetic patients. However, the molecular mechanisms underlying DBD remain elusive because of a lack of appropriate animal models. We demonstrate DBD in a mouse model that harbors hepatic-specific insulin receptor substrate 1 and 2 deletions (double knockout [DKO]), which develops type 2 diabetes. Bladders of DKO animals exhibited detrusor overactivity at an early stage: increased frequency of nonvoiding contractions during bladder filling, decreased voided volume, and dispersed urine spot patterns. In contrast, older animals with diabetes exhibited detrusor hypoactivity, findings consistent with clinical features of diabetes in humans. The tumor necrosis factor (TNF) superfamily genes were upregulated in DKO bladders. In particular, TNF-α was upregulated in serum and in bladder smooth muscle tissue. TNF-α augmented the contraction of primary cultured bladder smooth muscle cells through upregulating Rho kinase activity and phosphorylating myosin light chain. Systemic treatment of DKO animals with soluble TNF receptor 1 (TNFRI) prevented upregulation of Rho A signaling and reversed the bladder dysfunction, without affecting hyperglycemia. TNFRI combined with the antidiabetic agent, metformin, improved DBD beyond that achieved with metformin alone, suggesting that therapies targeting TNF-α may have utility in reversing the secondary urologic complications of type 2 diabetes.en
dc.language.isoen_USen
dc.publisherAmerican Diabetes Associationen
dc.relation.isversionofdoi:10.2337/db11-1763en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3402324/pdf/en
dash.licenseLAAen_US
dc.titleInhibition of TNF-α Improves the Bladder Dysfunction That Is Associated With Type 2 Diabetesen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalDiabetesen
dash.depositing.authorWang, Zongweien_US
dc.date.available2014-03-01T02:25:21Z
dc.identifier.doi10.2337/db11-1763*
dash.authorsorderedfalse
dash.contributor.affiliatedCheng, Zhiyong
dash.contributor.affiliatedGe, Rongbin
dash.contributor.affiliatedGomez, Pablo
dash.contributor.affiliatedOlumi, Aria
dash.contributor.affiliatedStrle, Klemen
dash.contributor.affiliatedSullivan, Maryrose
dash.contributor.affiliatedCristofaro, Vivian
dash.contributor.affiliatedWang, Zongwei
dash.contributor.affiliatedWhite, Morris
dash.contributor.affiliatedAdam, Rosalyn


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