Role of sorbitol in the up-regulation of urinary bladder M₂ 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 M₂ muscarinic receptor (M₂-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 M₂-mAChR protein and mRNA were compared between the treated and untreated diabetic rats. The densities of M₂-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 M₂mAChR 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.