Role of sorbitol in the up-regulation of urinary bladder M(2) muscarinic receptors in streptozotocin-induced diabetic rats.
This study investigated the role of sorbitol, a metabolic product of glucose, in the pathogenesis of rat diabetic cystopathy. Three-month-old male Wistar rats were divided into four groups: 1) normal controls; 2) rats rendered diabetic by streptozotocin; 3) rats fed with glucose; and 4) rats injected with sorbitol. The M(2) muscarinic receptor (M(2)-mAChR) protein and mRNA densities of the bladder tissue were measured by Western immunoblot and Northern blot, respectively. The streptozotocin-induced diabetic rats were then treated with ONO-2235, an aldose reductase inhibitor. The bladder M(2)-mAChR protein and mRNA were compared between the treated and untreated diabetic rats. The densities of M(2)-mAChR protein and mRNA in the bladder tissue were significantly increased in diabetic rats, and rats given either glucose or sorbitol (increases in receptor protein: 27.3 +/- 3.3, 19.8 +/- 2.3, and 18.0 +/- 2.1%; increases in mRNA: 39.6 +/- 3.7, 33.1 +/- 2.9, and 20.2 +/- 2.2%, respectively). When diabetic rats were treated with ONO-2235, the increases in bladder M(2)-mAChR protein and mRNA were significantly alleviated. The findings suggest that sorbitol plays a role in the pathogenesis of diabetic cystopathy in rats rendered diabetic by streptozotocin. Aldose reductase inhibitors may be useful in the treatment and prevention of diabetic cystopathy.
Tong
Yat-Ching
YC
Department of Urology, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC.
Chin
Wan-Tai
WT
Cheng
Juei-Tang
JT
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors; D000818:Animals; D001345:Autoradiography; D015152:Blotting, Northern; D015153:Blotting, Western; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D004234:Diuretics, Osmotic / Q000494:pharmacology*; D005947:Glucose / Q000494:pharmacology; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D043585:Receptor, Muscarinic M2; D011976:Receptors, Muscarinic / Q000235:genetics / Q000378:metabolism*; D012016:Reference Values; D012236:Rhodanine / Q000031:analogs & derivatives / Q000494:pharmacology; D013012:Sorbitol / Q000494:pharmacology*; D053778:Thiazolidines; D015854:Up-Regulation / Q000187:drug effects; D001743:Urinary Bladder / Q000187:drug effects / Q000378:metabolism*
D004234:Diuretics, Osmotic; D012333:RNA, Messenger; D043585:Receptor, Muscarinic M2; D011976:Receptors, Muscarinic; D053778:Thiazolidines; C038131:epalrestat; D013012:Sorbitol; D012236:Rhodanine; D000449:Aldehyde Reductase; D005947:Glucose