| Project/Area Number |
60304064
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| Research Category |
Grant-in-Aid for Co-operative Research (A)
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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 |
GOTO Yoshio Tohoku University School of Medicine, 医学部, 教授 (00004565)
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| Co-Investigator(Kenkyū-buntansha) |
KANAZAWA Yasunori Tokyo University School of Medicine, 医学部内科学第三講座, 講師 (10010399)
TOYOTA Takayoshi Tohoku University School of Medicine, 医学部内科学第三講座, 助教授 (40003628)
OKAMOTO Hiroshi Tohoku University School of Medicine, 医学部医化学第一講座, 教授 (60025632)
TARUI Seiichiro Osaka University School of Medicine, 医学部内科学第二講座, 教授 (00028341)
IMURA Hiroo Kyoto University School of Medicine, 医学部内科学第二講座, 教授 (10025570)
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| Project Period (FY) |
1985 – 1986
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| Project Status |
Completed (Fiscal Year 1986)
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| Budget Amount *help |
¥9,300,000 (Direct Cost: ¥9,300,000)
Fiscal Year 1986: ¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 1985: ¥6,700,000 (Direct Cost: ¥6,700,000)
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| Keywords | NOD mouse / Insulitis / Diabetic vascular complications / 自然発症糖尿病ラット(GKラット) |
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| Research Abstract |
1 Animal model and pathogenesis of diabetes: Spontaneous diabetic rats(GK) are well known as an animal model of non-insulin dependent diabetes(NIDDM). Recently rats who are injected by streptozotocin(100mg/kg) shortly after birth developed NIDDM. Deterioration of insulin secretion to glucose stimulus is characteristic in both diabetic rats. The reason of the impaired insulin secretion is unknown. Genetic factor, although still being not identified, reduces the number of pancreatic beta cells. NOD mice develop insulin dependent diabetes(IDDM), characterized by insulitis lesions and abnormal immune reaction. Pancreatic beta cell destruction may be caused by cell-specific cytotoxic T cells. OK-432 inhibited the development of diabetes in female NOD mice. The result indicates that OK-432 eliminates the specific cytotoxic T cells from the pancreatic islets. Okamoto'model is referred to the beta cell destruction owing to DNA damage. In this study "rig" which means rat insulinoma gene was discovered.
2 Diabetic complications: diabetic neuropathy and nephropathy are major complications as well as diabetic retinopathy. However, diabetic animals are difficult to develop the retinopathy. The pathological changes of the kidney were analyzed in monkeys, rats and mice. The thickened basement membrane of the glomerular capillaries were an initial change in any diabetic animals. Early events in the kidney were influenced by protein of diet. Metabolic derrangement of carbohydrate induces vascular changes. The storage of sorbitol which is converted from glucose by ardose reductase is a factor to initiate vasculasr degeneration. Therefore, aldose reductase inhibitor is expected to prevent the developoment of diabetic vascular complications.
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