| Project/Area Number |
18K06970
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 49010:Pathological biochemistry-related
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| Research Institution | Showa University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
篠崎 昇平 東京医科歯科大学, 大学院医歯学総合研究科, 非常勤講師 (40622626)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | GSNOR / iNOS / inflammation / anticoagulant / beta cell / S-nitrosylation / リバーロキサバン / diabetes |
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| Outline of Final Research Achievements |
S-nitrosoglutathione reductase (GSNOR) is an enzyme involved intracellular nitric oxide (NO) metabolism. In order to elucidate the novel role of GSNOR in pancreatic beta cells, we analyzed GSNOR overexpression in rat insulinoma cells and GSNOR KO mice. As the results, we found GSNOR overexpression cells have an anti-inflammatory effect by reducing a large amount of NO production. Using STZ-induced diabetic mouse model, we also found that blood glucose level in diabetic GSNOR KO mice was higher than diabetic WT mice. These mice exhibited increased apoptosis along with decreased expression of master regulator of pancreatic beta cells such as PDX-1. In addition, our study identified the anticoagulant rivaroxaban may have an antidiabetic effects through GSNOR activation in beta cells. Our results provide GSNOR might acts as a protective molecule in diabetic patients.
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| Academic Significance and Societal Importance of the Research Achievements |
わが国ではインスリン抵抗性は軽度であり、インスリン分泌低下を主体として2型糖尿病を発症することが多い。現在の糖尿病の薬物治療はインスリン注射やインスリン抵抗性改善薬などの治療薬が選択可能であるが、膵β細胞機能不全の進行を予防・治療する薬剤は存在しない。このようにわが国の2型糖尿病の原因治療のためには、膵β細胞機能不全を予防・治療する薬剤の開発が必要であり、今回の研究結果は、膵β細胞機能不全におけるGSNOR活性化の重要性を示唆するものであり、糖病病治療の新たな候補分子になるのではないかと考えている。
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