| Project/Area Number |
22K16400
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 54040:Metabolism and endocrinology-related
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| Research Institution | Yokohama City University |
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Principal Investigator |
Kyohara Mayu 横浜市立大学, 附属病院, 助教 (20828545)
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| Project Period (FY) |
2022-04-01 – 2024-03-31
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| Project Status |
Completed (Fiscal Year 2023)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2023: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2022: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | GLP-1 |
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| Outline of Research at the Start |
GLP-1は膵β細胞増殖の促進作用が報告されるが、その機序は不明な点も多い。申請者は、GLP-1受容体作動薬のリラグルチド刺激膵島のプロテオミクス解析を行い、外分泌腺の消化酵素Amy1や、膵腺房細胞に発現し膵β細胞へ作用する可能性が報告される分泌因子Reg1の発現上昇を見出した。申請者は、GLP-1による膵β細胞増殖における、膵島と腺房細胞との相互作用を介した新規経路の関与を提唱し、これを明らかとすることを本研究の目的とする。
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| Outline of Final Research Achievements |
GLP-1 enhances the β-cell proliferation of mouse islets. To identify a novel pathway of GLP-1-mediated β-cell proliferation, we conducted a quantitative proteomic analysis of mouse islets treated with GLP-1 receptor agonist (GLP-1RA). Pancreatic exocrine enzymes, such as Pancreatic alpha-amylase, were identified as up-regulated proteins by GLP-1RA treatment. We also identified that GLP-1RA augmented the expression of Lithostatin-1 (Reg-1) in islets. By co-culture of islets with acinar cells, the expression level of Reg-1 was significantly increased by GLP-1RA treatment in islets, and the expression levels of pancreatic alpha-amylase, and cell adhesion molecules were also significantly increased by GLP-1RA treatment in islets. It was suggested that GLP-1 promoted adhesion between islets and surrounding acinar cells, and interaction between islets and acinar cells potentially contributed to the GLP-1-mediated β-cell proliferation through mitotic action of Reg-1 from acinar cells.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究により、GLP-1による膵β細胞増殖作用において、膵島と腺房細胞の相互作用を介した新規経路の関与が示唆された。本研究の成果はGLP-1等のインクレチンを介した糖尿病治療における未解明の作用機序解明につながるとともに、膵β細胞増殖研究への貢献と、腺房細胞を標的とした糖尿病の新規治療法の開発へとつながる可能性がある。
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