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• W2323658873 abstract "You have accessJournal of UrologyBladder & Urethra: Anatomy, Physiology & Pharmacology II1 Apr 2016MP30-08 METABOLOMICS REVEALS DIFFERENTIAL CHANGES IN THE ENERGY GENERATING PATHWAYS OF THE DETRUSOR AND UROTHELIUM CAUSED BY DIABETES. Yi Wang, Gary Deng, and Kelvin Davies Yi WangYi Wang More articles by this author , Gary DengGary Deng More articles by this author , and Kelvin DaviesKelvin Davies More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.1240AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Few studies have investigated the impact of diabetes, on the energy generating pathways of the bladder detrusor and urothelium. Such studies might identify strategies that can ameliorate diabetic bladder pathophysiology. METHODS Streptozotocin was used to induce diabetes in 8 male Fischer rats for one month. Hyperglycemia was confirmed and urothelium and detrusor tissue isolated from both the diabetic and sixteen age matched non-diabetic bladder (controls). Metabolic profiling for each animal was performed by Metabolon Corp. ANOVA identified metabolites that differed significantly between groups and principal components analysis was used to reduce the dimension of the data. RESULTS Comparison of the metabolome of control urothelium and detrusor revealed differential metabolism between the tissues, reflecting their different physiological functions. With diabetes there was an expected elevation in both the urothelium and detrusor of glucose, lactate, 2-a-hydroxybutyrate, branched-chain amino acid degradation products and primary, secondary bile acids and a reduction in 1,5-anhydroglucitol. In the diabetic detrusor there was an overall activation of the pentose-phosphate and polyol pathways, whilst oxidative phosphorylation and glycolysis was reduced. Interestingly, overall diabetes had fewer effects on the urothelium, except for significantly increased intermediates of the TCA cycle and lipid metabolism. In the control detrusor, analysis of the metabolome suggested a negative feedback mechanism regulating the glycolytic pathway which was unchanged with diabetes. In the urothelium there is no evidence of negative feed-back in controls, but with diabetes there is a shift to negative feed-back of glycolysis. This suggests in the urothelium diabetes results in a change in expression or regulation of key enzymes involved in glycolysis. The metabolic profile provided evidence of oxidative stress after one month of diabetes; there was an elevation of the NADH/NAD ratio and compensatory increase in the GSH/GSSG ratio. CONCLUSIONS In addition to the expected effects of diabetes on bladder metabolism, there were striking differential changes caused by diabetes on the metabolism of detrusor and urothelium. The increased activity of the energy generating pathways in the detrusor would correlate with the reported over-activity of the diabetic bladder, whilst elevation of lysolipid and reduction of sphingolipid metabolism in the diabetic urothelium may alter membrane bioactivity (and thereby signaling mechanisms to the detrusor) as well as the barrier function of urothelium. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e414 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Yi Wang More articles by this author Gary Deng More articles by this author Kelvin Davies More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ..." @default.
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• W2323658873 title "MP30-08 METABOLOMICS REVEALS DIFFERENTIAL CHANGES IN THE ENERGY GENERATING PATHWAYS OF THE DETRUSOR AND UROTHELIUM CAUSED BY DIABETES." @default.
• W2323658873 doi "https://doi.org/10.1016/j.juro.2016.02.1240" @default.
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