The investigation of the mechanism of beta cell dedifferentiation aiming for new therapy of diabetes mellitus

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K21198
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pathological medical chemistry; Experimental pathology
• Research Institution: Yamaguchi University
• Principal Investigator: SHIINOKI Kikuko (阿望幾久子) 山口大学, 医学部, 助教(寄附講座等) (60609692)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 糖尿病 / 膵β細胞 / 脱分化 / Wfs1

Outline of Final Research Achievements

Wolfram syndrome, caused by the WFS1 gene mutations, is characterized by insulin-dependent diabetes mellitus. Genetically determined pancreatic β cell loss results from augmented ER and oxidative stresses. This study revealed that in the Wfs1-deficient mice β cells become dedifferentiated and revert to endocrine progenitor-like cells, and a subset of them takes α cell fate. It was also demonstrated that genetic inhibition of Txnip, which is a stress response molecule involving in various cellular processes, maintains β cell identity and completely prevents diabetes progression in the Wfs1-deficient mice. In this study, for the first time, we clearly showed a disease model that caused diabetes mainly due to β cell dedifferentiation, and identified a novel therapeutic target.

Free Research Field

分子病態学