The involvement of ER stress-induced Ca2+ signaling with the development of diabetes mellitus
| Project/Area Number |
17K07345
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Functional biochemistry
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| Research Institution | Teikyo Heisei University |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | Ca チャネル / 小胞体ストレス / 糖尿病 / TRPM2 / 酸化的ストレス / カルシウムシグナリング / 酸化ストレス / カルシウムシクナリング / シグナル伝達 / 生体分子 |
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| Outline of Final Research Achievements |
Oxidative stress induced TRPM2-dependent intracellular Ca2+ concentration increases in islets, although high glucose-induced intracellular Ca2+ concentration increases were TRPM2-independent. Next, we investigated the involvement of TRPM2 with the aggravation of diabetes mellitus by using diabetes model mice, Akita mice. Akita mouse has a mutation (Cys96Tyr) in the insulin 2 gene. The mutant insulin induce beta cell damage accompanied with ER stress, leading to the development of diabetes mellitus. Blood glucose elevation, glucose tolerance disorder, and the decrease of insulin secretion, and insulin content in islets observed in Akita mice were improved by Trpm2 deficiency.
These data suggested that TRPM2 is involved in the development of diabetes mellitus accompanied with ER stress-induced beta cell damage.
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| Academic Significance and Societal Importance of the Research Achievements |
現在二型糖尿病における β 細胞を標的にした薬としてインスリン分泌を促進させる薬が主に使用されている。しかしインスリン分泌を促進させ続けることは小胞体ストレスならび β 細胞障害を促進することにつながる。本申請研究では二型糖尿病の発症および増悪への TRPM2 の関与を明らかにし、β 細胞における二型糖尿病の発症および増悪を防ぐ創薬のターゲットとしてTRPM2 を提示できた。従って本申請研究により二型糖尿病発症に新たな側面からのアプローチを可能にし、新規創薬ターゲット分子を提示できたと言える。
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Report
(4 results)
Research Products
(1 results)
