Identification and treatment of targets that cause beta cell death by Wolfram Syndrome
| Project/Area Number |
18K08517
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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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| Review Section |
Basic Section 54040:Metabolism and endocrinology-related
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| Research Institution | Yamaguchi University |
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Principal Investigator |
Taguchi Akihiko 山口大学, 大学院医学系研究科, 助教 (20634744)
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| Project Period (FY) |
2018-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 小胞体ストレス / Wolfram症候群 / 糖尿病 / E4BP4 / Wolfram症候 / 時計遺伝子 / 概日リズム |
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| Outline of Final Research Achievements |
Wolfram syndrome (WFS) is a very rare disease characterized by juvenile-onset insulin-dependent diabetes mellitus and optic atrophy, and there is still no established treatment. Our group was first to identify the causative gene (WFS1). Since then, research on WFS has been conducted both in Japan and overseas, but the fundamental mechanism leading to a cure has yet to be elucidated. In this study, we focused on ATP2A2 as the mechanism by which WFS causes decreased insulin secretion, and found that ATPA2a2 activators had an insulin-promoting effect in mice with decreased insulin secretion.
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| Academic Significance and Societal Importance of the Research Achievements |
現在までWFSは根本的な治療法のない、難病である。WFSは細胞に小胞体ストレスという負荷がかかることで細胞死に至ると言われている。
今回同定したATP2A2活性化薬は、他施設では小胞体ストレスを改善する作用も報告されており、ATP2A2活性化薬はWFSのインスリン分泌作用のみならず、WFSの他の症状である視神経萎縮、難聴、精神障害などにも効果を発揮する可能性が期待できる。
WFS1遺伝子の変異・多型は、一般的な2型糖尿病でも検出されるものであり、WFSの治療が可能になれば、2型糖尿病への新たな治療法にもなりうる研究となった。
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Report
(5 results)
Research Products
(8 results)
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[Journal Article] P2Y1 purinergic receptor identified as a diabetes target in a small-molecule screen to reverse circadian β-cell failure2022
Author(s)
Marcheva B, Weidemann BJ, Taguchi A, Perelis M, Ramsey KM, Newman MV, Kobayashi Y, Omura C, Manning Fox JE, Lin H, Macdonald PE, Bass J.
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Journal Title
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Liver-specific dysregulation of clock-controlled output signal impairs energy metabolism in liver and muscle2021
Author(s)
Matsumura T, Ohta Y, Taguchi A, Hiroshige S, Kajimura Y, Fukuda N, Yamamoto K, Nakabayashi H, Fujimoto R, Yanai A, Shinoda K, Watanabe K, Mizukami Y, Kanki K, Shiota G, Tanizawa Y.
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Journal Title
Biochem Biophys Res Commun .
Volume: 534
Pages: 415-421
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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