| Project/Area Number |
60870011
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| Research Category |
Grant-in-Aid for Developmental Scientific Research
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| Allocation Type | Single-year Grants |
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| Research Field |
General medical chemistry
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| Research Institution | TOHOKU UNIVERSITY |
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Principal Investigator |
HYAHI Norio Tohoku University School of Medicine, 医学部, 教授 (00004606)
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| Co-Investigator(Kenkyū-buntansha) |
YONEMURA Yutaka Kanazawa University School of Medicine, 医学部, 講師 (20167042)
YAMAMOTO Hiroshi Tohoku University School of Medicine, 医学部, 助教授 (00115198)
OKAMOT Hiroshi Tohoku University School of Medicine, 医学部, 教授 (60025632)
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| Project Period (FY) |
1985 – 1987
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| Project Status |
Completed (Fiscal Year 1987)
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| Budget Amount *help |
¥10,500,000 (Direct Cost: ¥10,500,000)
Fiscal Year 1987: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1986: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1985: ¥7,000,000 (Direct Cost: ¥7,000,000)
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| Keywords | 90 % depancreatized rats / alloxan / streptozotocin / insulin-dependent diabetes / oxygen radicals / aromatic acid amides / regeneration of pancreatic <beta>-cells / 糖尿病治療藥 / アロキサン、ストレプトゾトシン / 膵ランゲルハンス島 / 再生膵B細胞 / reg(regenerating gene) / 糖尿病治療薬 / 膵切除ラット / 芳香族酸アミド / ラジカルスカベンジャー / DNA複製 |
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| Research Abstract |
1. Ninety % depancreatized rats exhibited glycosuria, glucose intolerance and degeneration of islet <beta>-cells in the remaining pancreas, thereby being regarded as a suitable model of insulin-dependent diabetes.
2. Radical scavengers such as superoxide dismutase protected islet <beta>-cells against DNA strand breakage induced by alloxan through generation of oxygen radicals,preventing the inhibition of insulion biosynthesis in the cells.
3. Aromatic acid amides such as nicotinamide and 3-aminobenzamide protected against alloxan-and streptozotocin-induced inhibition of insulion synthesis and prevented the development of diabetes. Aromatic acid amides were also found to induce regeneration of insulio-producing <beta>-cells, thereby ameliorating diabetes in 90 % depancreatized rats.
4. Nicotinamide at a dose of 500 mg/kg body weight i.p./day and 3-aminobenzamide at a dose of 100 mg/kg body wight i.p./day were the most effective in the prevention of the development of diabetes. No adverse side effects were noted with long-term consecutivbe administration of aromatic acid amides.
5. About 500 derivatives of aromatic acid amides were chemically synthesized, and administered per os to animal models of insulin-dependent diabetes and to nermal animals. Among the synthetic derivatives examined, pyridylbenzamides, especiallly 3-acy1-(6-methy1-)2-pyridylbenzamide and 3- ureido-(6-methy1-)2-pyridylbenzamide, were the most effective in both prevention and improvement of diabetes and had the least toxicity. The pyridylbenzamides were also found to inhibit platelet agglutination and aldose reductase, suggesting tht the compounds may be useful also for treating secondary changes due to diabetes.
Thus, in this research, we have successfully exploited a novel drug for the tratment and prevention of diabetes and its complications.
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