MP28-20 MUCOSA AFFECTS THE BLADDER DYSFUNCTION IN DIABETES WITH HIGH FAT DIET

Abstract

You have accessJournal of UrologyBladder & Urethra: Anatomy, Physiology & Pharmacology I1 Apr 2016MP28-20 MUCOSA AFFECTS THE BLADDER DYSFUNCTION IN DIABETES WITH HIGH FAT DIET Zongwei Wang, Vivian Cristofaro, Tongxiang Liu, Rongbin Ge, Maryrose Sullivian, and Aria Olumi Zongwei WangZongwei Wang More articles by this author , Vivian CristofaroVivian Cristofaro More articles by this author , Tongxiang LiuTongxiang Liu More articles by this author , Rongbin GeRongbin Ge More articles by this author , Maryrose SullivianMaryrose Sullivian More articles by this author , and Aria OlumiAria Olumi More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.1070AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Studies have demonstrated that obesity, diabetes and other metabolic syndromes are more vulnerable to develop bladder dysfunction. Previously we identified a diabetic bladder dysfunction (DBD) mouse model, in which hepatic specific double knockout insulin receptor substrate (IRS) 1 and 2 (DKO) causes insulin resistance and hyperglycemia but without development of obesity. These mice develop a temporal pattern of DBD that parallels the symptoms observed in humans. In this study we show the impact of high fat diet (HFD) on bladder function in diabetic mice and non-diabetic mice, and how the mucosa contributes to the bladder smooth muscle contractility. METHODS Female DKO mice and genetic control (CTR) were fed a standard chow (DKO, CTR) or a HFD (DKO+HFD, CTR+HFD) for 10 weeks. Urinary bladders were harvested from each animal for functional evaluation by ex vivo muscle tension studies. The mucosa was removed from half of each bladder. The amplitude of contractile responses induced by αβmethylene ATP (meATP), carbachol, KCl and electrical field stimulation (EFS) were measured. The contribution of the mucosa to the smooth muscle contractility was tested in bladder strips with and without the mucosal layer. RESULTS In bladder strips with intact mucosa, HFD did not affect contractions in response to CCh stimulation either in CTR or DKO. However, mucosa-denuded strips from DKO+HFD had significantly higher responses than that from normal diet animal, although HFD had little effect on CTR tissue without mucosa. Upon neurally-mediated responses evoked by EFS and membrane depolarization with KCl, bladder strip contractions in DKO+HFD with intact mucosa were not different from DKO fed standard chow, but significantly higher in mucosa-denuded tissue. Contrarily, the contractile responses to EFS in CTR+HFD were significantly higher than CTR, but little changed in mucosa-denuded tissue. Finally, HFD had little effect on aßmeATP elicited contractions either in CTR or DKO bladders with or without mucosa, although the contractions were higher in DKO bladder strips than CTR in normal chow. CONCLUSIONS Our data suggest that the effect of HFD appeared to be more pronounced in diabetic bladders than in control through cholinergic and neurogenic components but not purinergic component. More importantly, this augment of contractile responses was only observed in the absence of mucosa, which suggests that mucosa might have the protective effect in the condition of diabetes challenged with HFD. The data also suggest that diabetes patient might be more sensitive to HFD and vulnerable to develop bladder dysfunction. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e379 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Zongwei Wang More articles by this author Vivian Cristofaro More articles by this author Tongxiang Liu More articles by this author Rongbin Ge More articles by this author Maryrose Sullivian More articles by this author Aria Olumi More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...