| Project/Area Number |
20K17516
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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) |
2020-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2021: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2020: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | GLP-1 |
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| Outline of Research at the Start |
GLP-1は膵島においてグルコース応答性インスリン分泌に加え、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による膵β細胞増殖制御における新規経路の探索を目的に、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、膵外分泌腺の消化酵素である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であるReg1の発現上昇を見出した。
申請者は、GLP-1による膵β細胞増殖において、膵島と腺房細胞の相互作用による、Reg1を介した新たな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 cell proliferation in pancreatic β-cells. We conducted a quantitative proteomic analysis of mouse islets treated with GLP-1 receptor agonist liraglutide. Pancreatic exocrine enzymes, such as α-amylase 1 (Amy1), were identified as up-regulated proteins by liraglutide treatment. We also identified that liraglutide augmented the expression of Lithostatin-1 (Reg-1) in islets. Reg-1 predominantly expresses in pancreatic acinar cells, and regulates β-cell proliferation. By co-culture of isolated islets with acinar cells, the expression level of Reg-1, Amy1, and cell adhesion molecules, p-cadherin and connexin-26, were increased by liraglutide 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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