Optimization of beta-cell reprogramming driven by fasting-mimicking diet

2021 Fiscal Year Final Research Report

• Project/Area Number: 19H04060
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 59040:Nutrition science and health science-related
• Research Institution: Kitasato University (2021); Juntendo University (2019-2020)
• Principal Investigator: Miyatsuka Takeshi 北里大学, 医学部, 教授 (60622363)
• Co-Investigator(Kenkyū-buntansha): 綿田 裕孝 順天堂大学, 大学院医学研究科, 教授 (60343480)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: β細胞新生 / 再生医療 / 擬絶食療法 / Neurog3

Outline of Final Research Achievements

To monitor newly-generated beta cells, we generated Ins1-CreER;ROSA-mTmG (Ins1-neoTimer) mice, in which only newly-generated beta cells were labeled as green/red double-fluorescent cells. The Ins1-neoTimer mice were fed "fast-mimicking diet (FMD)", that is 50% of the standard daily calorie intake on day 1, 10% of normal daily calorie intake on days 2 to 4, and then normal chow for 1 week. Five cycles of FMD induced green/red double-fluorescent newborn beta cells in the islets of Ins1-neoTimer mice. As the newly generated beta cells were negative for Neurog3, which was not consistent with the previous finding that newly generated beta cells were derived from Neurog3-expressing endocrine progenitors.

Free Research Field

β細胞再生医療

Academic Significance and Societal Importance of the Research Achievements

近年、絶食に近い食事を間欠的に繰り返す”擬絶食療法”がβ細胞新生を誘導することが報告され(Chen C et al. Cell 168: 775-788, 2017)、糖尿病の新たな治療戦略として注目されている。今回我々はβ細胞新生を可視化できるIns1-CreER;ROSA-mTmG (Ins1-neoTimer) マウスを作製し、既報とほぼ同様の擬絶食療法がβ細胞新生を誘導することを明らかにした。ただし、β細胞新生量は十分ではなかった。高血糖是正を可能とする新生β細胞数を誘導するためには、さらなる実験条件の至適化が必要である。