TY - JOUR
T1 - Novel insights into development of diabetic bladder disorder provided by metabolomic analysis of the rat nondiabetic and diabetic detrusor and urothelial layer
AU - Wang, Yi
AU - Deng, Gary G.
AU - Davies, Kelvin P.
N1 - Publisher Copyright:
© 2016 the American Physiological Society.
PY - 2016/8/1
Y1 - 2016/8/1
N2 - 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 energygenerating 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.
AB - 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 energygenerating 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.
KW - Detrusor
KW - Diabetic bladder disorder
KW - Metabolism
KW - Metabolomics
KW - Urothelial
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U2 - 10.1152/ajpendo.00134.2016
DO - 10.1152/ajpendo.00134.2016
M3 - Article
C2 - 27354236
AN - SCOPUS:84983784168
SN - 0193-1849
VL - 311
SP - E471-E479
JO - American Journal of Physiology - Endocrinology and Metabolism
JF - American Journal of Physiology - Endocrinology and Metabolism
IS - 2
ER -