Uncovering molecular mechanisms in beta-cell neogenesis toward regeneration therapy for diabetes

2015 Fiscal Year Final Research Report

• Project/Area Number: 25461348
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Metabolomics
• 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)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 糖尿病 / 膵発生 / 再生医療 / インクレチン / β細胞

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.

Free Research Field

糖尿病再生医療