2022 Fiscal Year Final Research Report
Establishment of an experimental system to evaluate pancreatic beta-cell proliferation in vitro that can be utilized to identify anti-diabetes therapeutics targeting pancreatic beta-cell mass
| Project/Area Number |
21K19504
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Review Section |
Medium-sized Section 54:Internal medicine of the bio-information integration and related fields
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| Research Institution | Gifu University |
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Principal Investigator |
Yabe Daisuke 岐阜大学, 大学院医学系研究科, 教授 (60378643)
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| Co-Investigator(Kenkyū-buntansha) |
劉 彦言 岐阜大学, 大学院医学系研究科, 研究員 (10845796)
飯塚 勝美 藤田医科大学, 医学部, 教授 (40431712)
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| Project Period (FY) |
2021-07-09 – 2023-03-31
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| Keywords | 膵β細胞量 / 糖尿病 / 低分子化合物 / スクリーニング |
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| Outline of Final Research Achievements |
In this study, we established βFucci mice in which pancreatic β-proliferation can be observed in real time, and successfully cultured the isolated islet cells ex vivo for up to 1 week in 3D or 2D culture. In 2D culture, we examined various types of plates, and found that the Micro Slide I Luer plate manufactured by Nippon Genetics was the most suitable for stable culture, and the plate was able to contain 11.1 mM glucose in RPMI. We have confirmed that the addition of Harmine, a DYRK inhibitor known to proliferate pancreatic beta cells, to RPMI containing 11.1 mM glucose allows stable culture of pancreatic beta cells ex vivo, and have screened low molecular weight compounds using the assay system we established.
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| Free Research Field |
糖尿病学
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| Academic Significance and Societal Importance of the Research Achievements |
膵β細胞からのインスリン分泌の障害は糖尿病の発症や重症化を阻止するうえで克服すべき重要な課題である。インスリン分泌量は、個々の膵β細胞がインスリンを分泌する能力（膵β細胞機能）と膵β細胞の絶対量（膵β細胞量）の２つの因子により規定され前者に対しては、インクレチン薬やSU薬、グリニド薬が臨床の場で幅広く使用される。一方、後者に対しては、膵β細胞量調節の分子基盤の全容は依然不明であり、膵β細胞量を標的にした糖尿病の予防や治療の方法も一切存在しない。本研究で確立しえたスクリーニング系は、今後、膵β細胞量を標的とした予防や治療に資するシーズ探索に極めて有用なツールといえる。
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