| Project/Area Number |
62570514
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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 | Kurume University School of Medicine |
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Principal Investigator |
YAMADA Kentaro Kurume University School of Medicine, associate professor, 医学部, 助教授 (10191305)
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| Co-Investigator(Kenkyū-buntansha) |
NONAKA Kyohei Kurume University School of Medicine, professor, 医学部, 教授 (80028547)
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| Project Period (FY) |
1987 – 1988
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| Project Status |
Completed (Fiscal Year 1988)
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| Budget Amount *help |
¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1988: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1987: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Keywords | type I diabetes / islet cell / NOD mouse / cytokine / poly(ADP-ribose)合成酵素阻害剤 / poly(ADP-ribose) / 合成酵素阻害剤 / レクチン / γ-interferon / tumor necrosis factor |
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| Research Abstract |
This study was performed in order elucidate the mechanism of islet cell destruction in type I diabetes in vitro, and to develop the method of preventing the destruction. Since freshly isolated spleen cells of non-treated NOD mice did not damage islet cells in vitro, we used cyclophos-phamide-injected NOD mice. The number of spleen cells markedly decreased after a cyclophosphamide injection. Recovery of cell number was later in NOD mice than in Balb/c mice, suggesting the fragility of NOD mouse bone marrow. Surface marker studies showed that the increase of null cells was small in NOD mice, especially in the mice which developed diabetes afterwards, when compared to Balb/c mice.
Allokiller activity of NOD mouse spleen cells was almost normal. However, spleen cells of cyclophosphamide-injected NOD mice showed higher killing activity than those of cyclophosphamide-injected C3H mice. Spleen cells incubated with Con a destructed islet cells. Islet cell toxicity of Con A-stimulated cells was attenuated by poly(ADP-ribose) synthetase inhibitors, nicotinamide, picolinamide, and 3-aminobenzamide. Conditioned medium of spleen cells incubated with Con A showed islet cell toxicity, suggesting the involvement of cytokines in islet cell damage.
Islet cells were destructed when cultured in the presence of both interferon-r (IFN-r) and tumor necrosis factor (TNF) for 4 days. the cytokine-induced islet cell destruction was also prevented by poly(ADP-ribose) synthetase inhibitors.
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