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Recent investigations with experimental diabetic rats have provided evidence for the role of polyols in causing diabetic neuropathy, and an aldose reductase inhibitor which blocked the increase in polyols in nerve tissues was developed in order to prevent diabetic neuropathy.<BR>This report describes the effect of a newly synthesized and highly potent aldose reductase inhibitor, sorbinil (CP-45, 634), on peripheral nerve dysfunction in acutely diabetic rats.<BR>Male Sprague-Dawley rats weighing approximately 250g were used for the experiments. Diabetic rats were produced by the intravenous injection of streptozotocin (60mg/kg body weight). These rats of which the plasma glucose exceeded 250mg/dl persistently for 2 weeks, weredivided into three groups: non-treated diabetic, insulin-treated diabetic (8-16 U/day) and sorbinil-treated diabetic (20 mg/kg) rats.<BR>Plasma glucose, body weight and motor nerve conduction velocity (MNCV) were measured serially during the period of 2 weeks treatment. The sorbitol content of the sciatic nerve was measured at the end of the experiment.<BR>Delayed MNCV and accumulation of sorbitol in the sciatic nerves were observed in the nontreated diabetic rats. Insulin treatment was able to normalize the MNCV and sorbitol content. In the sorbinil-treated group, improvement of the MNCV and a reduction of the sorbitol content in the sciatic nerves were observed despite persistent hyperglycemia.<BR>These results indicate that abnormalities of the polyol pathway play an important role in the development of diabetic neuropathy, and sorbinil may represent a useful therapeutic agent against diabetic neuropathy.
- 一般社団法人 日本糖尿病学会の論文
一般社団法人 日本糖尿病学会 | 論文
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