Basic study on prevention and treatment of type 1 diabetes mellitus with biological respomse modifiers.
| Project/Area Number |
61570536
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
内分泌・代謝学
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| Research Institution | TOHOKU UNIVERSITY |
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Principal Investigator |
SATOH Jo Tohoku University Hospital, Tohoku University School of Medicine, 医学部付属病院, 助手 (60125565)
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| Co-Investigator(Kenkyū-buntansha) |
SHINTANI Shigeki Tohoku University Hospital, Tohoku University school of Medicine, 医学部付属病院, 医員
TOYOTA Takayoshi Tohoku University School of Medicine, 医学部, 助教授 (40003628)
下瀬川 徹 東北大学, 医学部附属病院, 医員
清水 文雄 東北大学, 歯学部, 助手 (10162710)
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| Project Period (FY) |
1986 – 1987
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| Project Status |
Completed (Fiscal Year 1987)
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| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1987: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1986: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Keywords | type 1 diabetes mellitus / IDDM / BRMs / OK-432 / NOD mouse / BB rat / 糖尿病の免疫療法 / 【I】型糖尿病 / インスリン依存型糖尿病 / 免疫修飾剤 |
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| Research Abstract |
We previously reported that a streptococcal preparation (OK-432), one of BRMs, inhibited insulitis and prevented insulin-dependent (type 1) diabetes mellitus (IDDM) in NOD mice. In this project, we extended our previous observation to two studies; 1) effect of OK-432 on IDDM in BB rats as an another model of IDDM and 2) analysis of mechanisms of OK-432-action by usingNOD mice. The results and conslusions are as follows.
1)The cumulative incidence of diabetes was 27.7% (13/47) by 30 weeks of age in BB rats, whereas that was significantly suppressed in the rats (7.4%, 4/54, p<0.01) who were weekly and intraperitoneally treated with 0.2 mg of OK-432. Histological examinations revealed that the OK-432-treated BB rats retained a greater number of intact islets without lymphocytic infiltrations than did thenon-treated rats. The cytotoxic activities of spleen cells directed against a rat insulinoma cell line, RIN, were significantly suppressed in the OK-432-treated BB rats as compared with tho
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se in the non-treated rats, Thus, the OK-432 treatment suppressed insulitis and inhibited development of diabetes not only in NOD mice but also in BB rats.
2) Approximately 85% of the non-treated NOD mice developed diabetes by 25 weeks of age. On the other hand, the weekly injection (ip or iv) of 0.1mg of OK-432 from 4 or 5 to 15 ro 20 weeks of age completely inhibited development of diabetes and these NOD mice did not develop diabetes even after ceasing the OK-432-treatment. Cyclophosphamide enhanced the development of diabetes in thenon-treated NOD mice but not in the OK-432-treated mice. The diabetes wastransfered by the spleen cells from the non-treated NOD mice but not by the cells from the OK-432-treated mice. In addition, the spleen cells from the OK-432-treated mice inhibited the development of diabetes in the cyclophosphamide-treated mice and this inhibitory effect was eliminated by the treatment of cells with anti-Thy-1 antibody and complement. These indicate that the OK-432-treatment inhibited the induction of cytotoxic effector cells directed against pancreatic B cells and this effect was mediated by suppressor T cells. Less
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Report
(2 results)
Research Products
(12 results)
