Role of sorbitol in the up‐regulation of urinary bladder M₂ muscarinic receptors in streptozotocin‐induced diabetic rats

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.

Ultra-structural morphological abnormalities of the urinary bladder in streptozotocin-induced diabetic female rats

“…Urinary bladder de-afferentiation causes reduced awareness of bladder filling and bladder atony with impaired detrusor function and detrusor areflexia [5][6][7][12][13][14]. However, almost a quarter of affected patients may also have detrusor overactivity without evidence of areflexia [1][2][3][5][6][7][8]. The ultra-structural pattern of lesions identified in the detrusor muscle of our diabetic group concurred with muscle dysjunction and indicate that detrusor overactivity may be the main clinical features of diabetes-induced bladder dysfunction [1-3, 5-8, 16, 17].…”

“…Autonomic neuropathy occurs in diabetic patients, mainly insulin-dependent diabetics, with a cumulative increase in prevalence over time that rises to 50% after 25 years [1][2][3][4][5][6][7][8]. Bladder dysfunction is the commonest form of neuropathy and affects up to 40-80% of diabetic patients [1][2][3][4][5][6][7][8][9][10].…”

“…Bladder dysfunction is the commonest form of neuropathy and affects up to 40-80% of diabetic patients [1][2][3][4][5][6][7][8][9][10]. The disease has a slowly progressive and insidious course that is characterized by decreased bladder sensation and either impaired or unstable detrusor contractions [1][2][3][4][5][6][7][8][9][10][11][12]. Most patients, however, remain asymptomatic and therefore diabetes-induced bladder dysfunction is difficult to detect and treat in its early stages [1,2,5,7,8,10].…”

“…Laboratory animals, which are genetically diabetic and those with chemically induced diabetes lend themselves as useful models to study normal bladder function and experimentally induced dysfunctions [6,[11][12][13][14][20][21][22][23]. They provide the unique opportunity to investigate the role of specific disease conditions (e.g.…”

Diabetic cystopathy

“…The M3 receptor is the major muscarinic receptor in the bladder and is responsible for detrusor contraction. Sorbitol has been shown in the diabetic rat model to cause overexpression of the M2 receptor in the bladder [33]. Although the physiological role of the M2 receptor is not completely clear, it is hypothesized that the M2 receptor is responsible for causing indirect contraction of the detrusor muscle by reversing the sympathetically mediated detrusor relaxation [34].…”