2021 Fiscal Year Final Research Report
Mechanism of proliferation, differentiation, and dedifferentiation of pancreatic beta-cells induced by local signals
| Project/Area Number |
19K07281
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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 48020:Physiology-related
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| Research Institution | Chiba University |
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Principal Investigator |
MIKI Takashi 千葉大学, 大学院医学研究院, 教授 (50302568)
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| Co-Investigator(Kenkyū-buntansha) |
李 恩瑛 千葉大学, 大学院医学研究院, 助教 (60583424)
波多野 亮 千葉大学, 大学院医学研究院, 助教 (60521713)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Keywords | 糖尿病 / 膵島再生 / 膵β細胞 / 前駆細胞 |
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| Outline of Final Research Achievements |
Diabetes mellitus is a metabolic disorder characterized by chronic hyperglycemia, and deterioration of pancreatic beta-cells both in quantity and in quality is central to its pathophysiology. By contrast, mass and function of beta-cells are known to be unaltered throughout live in healthy subjects. Therefore, medical intervention to recover their mass and function can be its radical therapy. However, its precise mechanism remains unknown. In the present study, we elucidated the mechanism of beta-cell regeneration by using our murine model of beta-cell ablation. As a result, we found that beta-cell reduction triggers the proliferation of the residual beta-cells, and that the mode of beta-cell regeneration differs depending on the local cellular circumstances during regeneration. Notably, alteration in cellular arrangement inside the islets triggers the active, repetitive cell proliferation of a small number of beta-cells through de-differentiation, proliferation, and re-differentiation.
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| Free Research Field |
医学
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| Academic Significance and Societal Importance of the Research Achievements |
膵島再生は糖尿病の根治治療となり得るが、実際の生体で、膵β細胞が膵島再生を担うだけの十分な再生能を有しているのか。どの様な方法で再生を人為的に誘導できるのかなど、基本的な疑問が未解決である。正常状態での膵島量の制御機構と、膵β細胞の増殖機構を解明することは、これらの課題を解決する上で、不可欠な学術的な基盤である。今回の結果は、成体のマウスにおいては反復して細胞分裂が可能な膵β細胞が存在することが示され、膵島再生による糖尿病の根治治療の可能性を指示する結果となった。また、再生誘導法の違いにより異なった機序の再生が惹起されることが示された点も重要な成果であると考えている。
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