| Project/Area Number |
15K21198
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Pathological medical chemistry
Experimental pathology
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| Research Institution | Yamaguchi University |
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Principal Investigator |
SHIINOKI Kikuko 山口大学, 医学部, 助教(寄附講座等) (60609692)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 糖尿病 / 膵β細胞 / 脱分化 / Wfs1 / β細胞脱分化 / 膵β細胞不全 / WFS1 |
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| 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.
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