Role of sorbitol in the up-regulation of urinary bladder M(2) muscarinic receptors in streptozotocin-induced diabetic rats

Neurourol Urodyn. 2002;21(2):154-9. doi: 10.1002/nau.10028.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aldehyde Reductase / antagonists & inhibitors
  • Animals
  • Autoradiography
  • Blotting, Northern
  • Blotting, Western
  • Diabetes Mellitus, Experimental / metabolism*
  • Diuretics, Osmotic / pharmacology*
  • Glucose / pharmacology
  • Male
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Wistar
  • Receptor, Muscarinic M2
  • Receptors, Muscarinic / genetics
  • Receptors, Muscarinic / metabolism*
  • Reference Values
  • Rhodanine / analogs & derivatives
  • Rhodanine / pharmacology
  • Sorbitol / pharmacology*
  • Thiazolidines
  • Up-Regulation / drug effects
  • Urinary Bladder / drug effects
  • Urinary Bladder / metabolism*

Substances

  • Diuretics, Osmotic
  • RNA, Messenger
  • Receptor, Muscarinic M2
  • Receptors, Muscarinic
  • Thiazolidines
  • epalrestat
  • Sorbitol
  • Rhodanine
  • Aldehyde Reductase
  • Glucose