| Project/Area Number |
10671036
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Endocrinology
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| Research Institution | The University of Tokushima |
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Principal Investigator |
YAMAOKA Takashi The University of Tokushima, Institute for Genome Research, Division of Genetic Information, Associate Professor, ゲノム機能研究センター, 助教授 (40263826)
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| Co-Investigator(Kenkyū-buntansha) |
SUGINO Hiromu The University of Tokushima, Institute for Enzyme Research, Professor, 分子酵素学研究センター, 教授 (50211305)
NOJI Sumihare The University of Tokushima, Department of Biological Science and Technology, Professor, 工学部, 教授 (40156211)
ITAKURA Mitsuo The University of Tokushima, Institute for Genome Research, Division of Genetic Information, Professor, ゲノム機能研究センター, 教授 (60134227)
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| Project Period (FY) |
1998 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 2000: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1999: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1998: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Keywords | Pancreatic islets / Pancreatic β cells / Transgenic mouse / TGF-β / Activin / Interferon-γ / Pax6 / Reg I / 糖尿病 / アポトーシス / 腫瘍発生 / 発生工学 / サイトカイン / Pax-6 |
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| Research Abstract |
(1) Glucagon promoter/active TGF-β-transgenic NOD mouse : The rate of onset of type 1 diabetes decreased because of T-cell suppression by TGF-β, and islet hypoplasia was induced by the suppressive effect of TGF-β on the growth of islets.
(2) Insulin promoter/dominant negative, constitutively active, or normal activin receptor-transgenic mice : In transgenic mice expressing activin-receptor mutants, islets were hypoplastic, whereas transgenic mice expressing normal activin receptor did not show any abnormality. Therefore, appropriate intensity of activin signal is necessary for normal development of islets.
(3) Glucagon promoter/interferon-γ-transgenic mouse : Interferon-γ directly impaired β cells without lymphocytes and stimulated the proliferation of immature β-cells, leading to islet remodeling.
(4) Insulin promoter or Pdx1 promoter/Pax6-transgenic mice : In insulin promoter/Pax6-transgenic mice, β-cell differentiation was impaired. In Pdx1 promoter/Pax6-transgenic mice, epithelial hyperplasia of pancreatic ducts and cystic adenoma were observed, in addition to the decrease in the number of β cells. It was suggested that Pax6 has a dual action on islet development : one is the stimulation of proliferation of islet precursor cells and the other is the induction of α-cell phenotypes.
(5) Glucagon promoter/Reg I-transgenic mouse : Overexpression of Reg I induced β-cell apoptosis, and diabetes. Furthermore, excessive secretion of Reg I resulted in diverse malignant tumors. The tumor-promoting activity of Reg I protein should be considered for its possible clinical applications.
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