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- Title
Amelioration of nerve Na(+)-K(+)-ATPase activity independently of myo-inositol level by PGE1 analogue OP-1206.alpha-CD in streptozocin-induced diabetic rats.
- Authors
Sonobe, Masanobu; Yasuda, Hitoshi; Hisanaga, Takashi; Maeda, Kengo; Yamashita, Makio; Kawabata, Toru; Kikkawa, Ryuichi; Taniguchi, Yuzo; Shigeta, Yukio; Sonobe, M; Yasuda, H; Hisanaga, T; Maeda, K; Yamashita, M; Kawabata, T; Kikkawa, R; Taniguchi, Y; Shigeta, Y
- Abstract
An oral prostaglandin E1 (PGE1) analogue, OP-1206.alpha-CD, was given to rats with streptozocin (STZ)-induced diabetes to examine the therapeutic effects of OP-1206 on short-term and long-term diabetic neuropathy and its action mechanism with special reference to nerve Na(+)-K(+)-ATPase activity. In the short-term experiment, OP-1206 was administered daily to diabetic rats in 3- and 30-mg/kg doses for 4 wk from the day of STZ injection. In the long-term study, 10 micrograms/kg OP-1206 was also given daily for 8 wk from 7 mo after induction of diabetes. The compound improved decreased sciatic motor nerve conduction velocity in both short-term and long-term diabetic rats. The nerve Na(+)-K(+)-ATPase activity of diabetic rats, reduced by 40% compared with controls, was reversed to the level of controls in both experiments, whereas weight loss and hyperglycemia were unchanged, and neither nerve sorbitol accumulation nor myo-inositol depletion was corrected. In a morphometric analysis of myelinated nerve fibers (MNFs) in long-term diabetes, the mean diameter of the largest 10% of MNFs was significantly reduced in untreated diabetic compared with control rats, but OP-1206 completely reversed this reduction. The results suggest that OP-1206 ameliorates a decrease in nerve Na(+)-K(+)-ATPase activity without any effect on nerve myo-inositol level and that the compound may be not only a potent therapeutic agent for the treatment of diabetic neuropathy but also a useful research tool to investigate the mechanism of nerve Na(+)-K(+)-ATPase activity regulation.
- Publication
Diabetes, 1991, Vol 40, Issue 6, p726
- ISSN
0012-1797
- Publication type
journal article
- DOI
10.2337/diabetes.40.6.726