| Project/Area Number |
18K16195
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 54040:Metabolism and endocrinology-related
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| Research Institution | Shiga University of Medical Science |
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Principal Investigator |
Ida Shogo 滋賀医科大学, 医学部, 客員助教 (90792028)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 膵β細胞 / 膵α細胞 / O-GlcNAc修飾 / 翻訳後修飾 / β細胞 / α細胞 / 膵島 |
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| Outline of Final Research Achievements |
Post-translational modifications play a critical role in regulating physiological cellular functions. One of the post-translational modifications, called O-GlcNAcylation, has been known that it is closely related to the pathogenesis of diabetic complication, however, the its role in pancreatic islets which has the central role in glucose metabolism is still unknown. Thus, we attempted to identify the role of O-GlcNAcylation in pancreatic beta cells using pancreatic beta cells-specific Ogt knock out mice (Ogt-bKO).
In Ogt-bKO finally showed the beta cell destruction and insulin depletion due to various stresses such as ER stress and oxidative stress, suggesting O-GlcNAcylation is essential to maintain the homeostasis in pancreatic beta cells. Additionally, we found Ogt-bKO mice transiently increase insulin secretion, and cDNA microarray analysis revealed various gene alteration during that period.
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| Academic Significance and Societal Importance of the Research Achievements |
糖尿病は高血糖に起因した細胞内代謝障害に伴い生じる全身性疾患であり、近年、その患者数は世界中で急激に増加している。膵島はインスリンやグルカゴン分泌を介して糖代謝制御の中心的役割を担っており、その理解を深めることは糖尿病病態の理解および新規の糖尿病治療を探索するにあたり非常に重要である。本研究はO-GlcNAc修飾という蛋白の翻訳後修飾に着目し、膵島における同修飾の役割を明らかにすることで糖尿病の病態理解や治療に寄与するものである。
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