Novel insights into development of diabetic bladder disorder provided by metabolomic analysis of the rat nondiabetic and diabetic detrusor and urothelial layer.
Am J Physiol Endocrinol Metab
; 311(2): E471-9, 2016 08 01.
Article
in En
| MEDLINE
| ID: mdl-27354236
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 ß-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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Urinary Bladder
/
Urinary Bladder Diseases
/
Urothelium
/
Diabetes Mellitus, Experimental
/
Diabetes Mellitus, Type 1
/
Metabolomics
/
Muscle, Smooth
Type of study:
Etiology_studies
/
Observational_studies
/
Risk_factors_studies
Limits:
Animals
Language:
En
Journal:
Am J Physiol Endocrinol Metab
Journal subject:
ENDOCRINOLOGIA
/
FISIOLOGIA
/
METABOLISMO
Year:
2016
Document type:
Article
Publication country:
EEUU
/
ESTADOS UNIDOS
/
ESTADOS UNIDOS DA AMERICA
/
EUA
/
UNITED STATES
/
UNITED STATES OF AMERICA
/
US
/
USA