| Project/Area Number |
18K08491
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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 54040:Metabolism and endocrinology-related
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| Research Institution | Jikei University School of Medicine |
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Principal Investigator |
Fujimoto Kei 東京慈恵会医科大学, 医学部, 准教授 (40372974)
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| Project Period (FY) |
2018-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
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| Keywords | 膵α細胞 / グルカゴン / PKCδ |
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| Outline of Final Research Achievements |
In cellular experiments, glucagon secretion was examined using glucagon-secreting cell lines. We showed that PKCδ positively regulated arginine-induced glucagon secretion using inhibitor and siRNA for PKCδ. In animal experiments, we have established pancreatic α-cell-specific PKCδ knockout (αPKCδKO) mice, which revealed decreased arginine-induced glucagon secretion. In addition, arginine-induced glucagon secretion was decreased in islets isolated from αPKCδKO mice as well. In summary, we showed that PKCδ is pivotal molecule in arginine-induced glucagon secretion.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究により細胞および生体レベルで膵α細胞からのグルカゴン分泌にPKCδが関与することが示唆された。元来、グルカゴンは血糖を上昇させることが知られており、今後より詳細なPKCδ依存性グルカゴン分泌の分子機序を明らかにすることで、PKCδを標的とした糖尿病診断や糖尿病治療に繋がる可能性がある。
また、PKCδは腎症と網膜症の発症・進展、骨格筋細胞のインスリン抵抗性にも関与している。よって本研究は、糖尿病におけるグルカゴン分泌異常や耐糖能異常だけでなく合併症予防をも見据えた可能性を有している。
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