title: Novel insights into development of diabetic bladder disorder provided by metabolomic analysis of the rat nondiabetic and diabetic detrusor and urothelial layer.
abstract: There are at present no published studies providing a global overview of changes in bladder metabolism resulting from diabetes. Such studies have the potential to provide mechanistic insight into the development of diabetic bladder disorder (DBD). In the present study, we compared the metabolome of detrusor and urothelial layer in a 1-mo streptozotocin-induced rat model of type 1 diabetes with nondiabetic controls. Our studies revealed that diabetes caused both common and differential changes in the detrusor and urothelial layer's metabolome. Diabetes resulted in similar changes in the levels of previously described diabetic markers in both tissues, such as glucose, lactate, 2-hydroxybutyrate, branched-chain amino acid degradation products, bile acids, and 1,5-anhydroglucitol, as well as markers of oxidative stress. In the detrusor (but not the urothelial layer), diabetes caused activation of the pentose-phosphate and polyol pathways, concomitant with a reduction in the TCA cycle and β-oxidation. Changes in detrusor energy-generating pathways resulted in an accumulation of sorbitol that, through generation of advanced glycation end products, is likely to play a central role in the development of DBD. In the diabetic urothelial layer there was decreased flux of glucose via glycolysis and changes in lipid metabolism, particularly prostaglandin synthesis, which also potentially contributes to detrusor dysfunction.
authors.affiliation: Department of Urology, Albert Einstein College of Medicine, Bronx, New York;
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Endocrine/Cardiovascular Research, Lilly Research Laboratories, Indianapolis, Indiana; and.
authors.forename: Gary G
authors.initials: GG
authors.lastname: Deng
authors.affiliation: Department of Urology, Albert Einstein College of Medicine, Bronx, New York; Department of Physiology and Biophysics, Albert Einstein College of Medicine, Bronx, New York kelvin.davies@einstein.yu.edu.
authors.forename: Kelvin P
authors.initials: KP
authors.lastname: Davies
mesh_terms: D000597:Amino Acids, Branched-Chain / Q000378:metabolism; D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism; D016022:Case-Control Studies; D002952:Citric Acid Cycle; D003847:Deoxyglucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006019:Glycolysis; D006885:Hydroxybutyrates / Q000378:metabolism; D019344:Lactic Acid / Q000378:metabolism; D050356:Lipid Metabolism; D008297:Male; D055432:Metabolomics; D009130:Muscle, Smooth / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010427:Pentose Phosphate Pathway; D011108:Polymers / Q000378:metabolism; D011453:Prostaglandins / Q000096:biosynthesis; D051381:Rats; D011916:Rats, Inbred F344; D013012:Sorbitol / Q000378:metabolism; D001743:Urinary Bladder / Q000378:metabolism*; D001745:Urinary Bladder Diseases / Q000209:etiology / Q000378:metabolism*; D019459:Urothelium / Q000378:metabolism*
chemical_list: D000597:Amino Acids, Branched-Chain; D001647:Bile Acids and Salts; D017127:Glycation End Products, Advanced; D006885:Hydroxybutyrates; D011108:Polymers; D011453:Prostaglandins; C024617:polyol; D019344:Lactic Acid; D013012:Sorbitol; C006584:1,5-anhydroglucitol; D003847:Deoxyglucose; D005947:Glucose; C031570:2-hydroxybutyric acid
keywords: detrusor; diabetic bladder disorder; metabolism; metabolomics; urothelial