Regulation of beta cell fate during dedifferentiation
| Project/Area Number |
20K08866
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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 | Gunma University |
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Principal Investigator |
Shirakawa Jun 群馬大学, 生体調節研究所, 教授 (70625532)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2022: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 糖尿病 / 膵β細胞 / 代謝学 / 内分泌学 / 分化転換 / 交感神経 / 膵島 / 不均一性 |
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| Outline of Research at the Start |
糖尿病における膵β細胞の機能障害の１つとして、膵β細胞の脱分化および膵α細胞などの非β膵島細胞への分化転換が挙げられる。しかし、膵β細胞がどの細胞に分化するのか、その細胞運命の決定機構は全く不明であるため、膵島ホルモンを適切に制御する効果的な治療法の開発に至っていない。本研究では、膵β細胞を含む膵島が、空間的位置により異なる機能をもつサブタイプに分けられ、この膵島の不均一性が、膵β細胞の分化転換過程における細胞運命の決定機構に関与することを見出し、膵β細胞の細胞運命決定因子を明らかにすることにより、新規糖尿病治療法の開発を目指す。
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| Outline of Final Research Achievements |
A major pancreatic beta cell damage in diabetes is the dedifferentiation of beta cells and transdifferentiation into non-beta islet cells such as alpha cells. However, it has been unknown how beta cells differentiate and how cell fate is determined. In this study, we investigated molecular mechanisms underlying cell fate determination that induce pancreatic alpha, delta, and PP cells in the process of beta cell transdifferentiation in diabetes conditions. As a result, we elucidated the mechanism mediated by the sympathetic nervous system that determines the direction of transdifferentiation of beta cells in the pancreatic tissue.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究は、膵β細胞が、膵α細胞になるのか、膵PP細胞になるのかという、膵β細胞分化転換における細胞運命決定の分子機構を明らかにするという既存の概念にはない膵β細胞機能不全のメカニズムに迫ることができた。糖尿病における膵β細胞の障害過程において、それぞれのサブタイプにおける膵β細胞の細胞運命決定の分子機構が解明されると、この分化転換を制御することがで、糖尿病状態において機能的な膵β細胞量の維持ならびに増加につながると考えられ、糖尿病発症・進展過程における新規治療法の開発に寄与するものと期待される。
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Report
(4 results)
Research Products
(40 results)
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[Journal Article] E2F1 transcription factor mediates a link between fat and islets to promote β cell proliferation in response to acute insulin resistance.2022
Author(s)
Shirakawa J, Togashi Y, Basile G, Okuyama T, Inoue R, Fernandez M, Kyohara M, De Jesus DF, Goto N, Zhang W, Tsuno T, Kin T, Pan H, Dreyfuss JM, Shapiro AMJ, Yi P, Terauchi Y, Kulkarni RN.
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Journal Title
Cell Rep.
Volume: 41(1)
Issue: 1
Pages: 111436-111436
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Protective effects of S100A8 on sepsis mortality: Links to sepsis risk in obesity and diabetes.2022
Author(s)
Miyashita D, Inoue R, Tsuno T, Okuyama T, Kyohara M, Nakahashi-Oda C, Nishiyama K, Fukushima S, Inada Y, Togashi Y, Shibuya A, Terauchi Y, Shirakawa J.
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Journal Title
iScience
Volume: 25(12)
Issue: 12
Pages: 105662-105662
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Luseogliflozin Increases Beta Cell Proliferation Through Humoral Factors That Activate an Insulin Receptor- And IGF-1 Receptor-Independent Pathway2020
Author(s)
Shirakawa J, Tajima K, Okuyama T, Kyohara M, Togashi Y, De Jesus DF, Basile G, Kin T, Shapiro AMJ, Kulkarni RN, Terauchi Y.
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Journal Title
Diabetologia
Volume: 63
Issue: 3
Pages: 577-587
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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