| Project/Area Number |
10833001
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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 |
免疫の制御機構
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| Research Institution | Osaka University |
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Principal Investigator |
KONO Norio Osaka University, Faculty of Medicine, Professor, 医学部, 教授 (30093412)
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| Co-Investigator(Kenkyū-buntansha) |
HANAFUSA Toshiaki Osaka University, Graduate School of Medicine, Assistant Professor, 医学系研究科, 講師 (60164886)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 1999: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1998: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Keywords | Type 1 diabetes mellitus / Autoimmunity / Fas / Fas ligand / Betacellulin / インスリン依存性糖尿病 / NODマウス / Fas-FasL系 / Perforin |
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| Research Abstract |
1. Research on the involvement of Fas-Fas ligand system in type 1 diabetes mellitus
To clarify whether or not the Fas-Fas ligand (FasL)system is involved in the β-cell destruction in human type 1 diabetes, we immunohistochemically analyzed pancreatic biopsy specimen of 13 recent-onset patients. We found that 6 patients had insulitis with Fas expression in both the islets and infiltrating cells. Incidence of Fas positive cells as higher in β-cells than in α-cells. We also found that FasL was expressed exclusively in islet-infiltrating cells. Most prevalent phenotype of FasL positive cells was CD8. We could not detect any Fas-FasL expression in the patients without insulitis.
2. Research on the expression of betacellulin in human pancreas and islet tumor cell lines
We immunohistochemically analyzed the expression of betacellulin in human pancreatic tissue and islet cell tumors. We found betacellulin was expressed in α-cells and duct cells, and probably in β-cells in normal human adulttissue. In fetal tissue, strong immunoreactivity to betacellulin was detected in primitive pancreatic duct cells. Both glucagonoma and insulinoma cells also showed positive immunoreactivity to betacellulin. These results suggest that betacellulin may have physiologically important roles such as growth and differentiation of islet cells in human pancreas.
3. Research on a novel subtype of type 1 diabetes mellitus
We found that some patients with idiopathic type 1 diabetes show a nonauto-immune, fulminant disorder characterized by the absence of insulitis and of diabetes-related antibodies, a remarkably abrupt onset, and high serum pancreatic enzyme concentration.
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