The role of sorbitol pathway and treatment effect of aldose reductase inhibitor ONO2235 in the up-regulation of cardiac M2-muscarinic receptors in streptozotocin-induced diabetic rats

Tsang Pai Liu, Shiow Wen Juang, Juei Tang Cheng, Yat-Ching Tong

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This study investigated the role of the sorbitol pathway on the genetic up-regulation of the cardiac M2 muscarinic receptor (M 2-mAChR) in streptozotocin (STZ)-induced diabetic rats. Three-month-old male Wistar rats were divided into five groups: (1) normal controls; (2) rats rendered diabetic by streptozotocin; (3) rats fed with glucose; (4) rats injected with sorbitol; and (5) diabetic rats treated with ONO-2235, an aldose reductase inhibitor. The M2 muscarinic receptor (M2-mAChR) protein and mRNA densities of the heart tissue were measured by Western immunoblotting and Northern blotting, respectively. The densities of M2-mAChR protein and mRNA in the heart were significantly increased in diabetic rats, and rats given either glucose or sorbitol. When diabetic rats were treated with ONO-2235, the increases in heart M2-mAChR protein and mRNA were significantly reduced. The findings suggest that hyperglycemia and the sorbitol pathway are involved in the pathogenesis of diabetic heart disease in STZ-induced diabetic rats. Aldose reductase inhibitors may be useful in the treatment and prevention of cardiac complication in diabetes.

Original languageEnglish
Pages (from-to)131-135
Number of pages5
JournalNeuroscience Letters
Issue number1-2
Publication statusPublished - 2005 Jul 22


All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

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