Uncovering molecular mechanisms in beta-cell neogenesis toward regeneration therapy for diabetes
Project/Area Number |
25461348
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Metabolomics
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Research Institution | Juntendo University |
Principal Investigator |
Miyatsuka Takeshi 順天堂大学, 医学(系)研究科(研究院), 准教授 (60622363)
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Project Period (FY) |
2013-04-01 – 2016-03-31
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Project Status |
Completed (Fiscal Year 2015)
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Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2015: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2013: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
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Keywords | 糖尿病 / 膵発生 / 再生医療 / インクレチン / β細胞 / reprogramming / GLP-1 / Gpr158 / Pdx1 / Neurog3 / Mara / neogenesis / インスリン / マイクロアレイ / 転写因子 / β細胞分化 / β細胞新生 |
Outline of Final Research Achievements |
To analyze newly-generated β cells with better time resolution, we developed the reporter mouse models“Insulin-Timer", which permitted sequential analyses of the sorted endocrine progenitors and revealed their unique features [Miyatsuka et al. Diabetes 63: 3388-3393, 2014]. Furthermore, microarray analysis identified genes specifically expressed in endocrine progenitors during development. Among these genes, we focused on GLP-1 receptor (Glp1r), which plays an essential role in acinar-to-β reprogramming and generated the transgenic mouse model "exo-Glp1r", which expressed Glp1r exclusively in exocrine cells. When exo-Glp1r mice were treated with the GLP-1 analogs exendin-4 and gastrin, a fraction of the exocrine cells were reprogrammed into insulin-producing cells. The exocrine-derived β cells formed islet-like clusters in the pancreata of exo-Glp1r mice. These findings propose possible directions of future therapies for generating β cells via these signaling pathways.
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Report
(4 results)
Research Products
(7 results)
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[Journal Article] Sustained expression of GLP-1 receptor differentially modulates beta-cell functions in diabetic and nondiabetic mice.2016
Author(s)
Kubo F, Miyatsuka T, Sasaki S, Takahara M, Yamamoto Y, Shimo N, Watada H, Kaneto H, Gannon M, Matsuoka TA, Shimomura I
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Journal Title
Biochem Biophys Res Commun.
Volume: 471
Issue: 1
Pages: 68-74
DOI
Related Report
Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] 5. Activation of GLP-1 and gastrin signalling induces in vivo reprogramming of pancreatic exocrine cells into beta cells in mice.2015
Author(s)
Sasaki S, Miyatsuka T, Matsuoka TA, Takahara M, Yamamoto Y, Yasuda T, Kaneto H, Fujitani Y, German MS, Akiyama H, Watada H, Shimomura I.
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Journal Title
Diabetologia
Volume: 58
Issue: 11
Pages: 2582-2591
DOI
Related Report
Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
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