Analysis of genes specifically repressed in mature beta-cells of pancreas
| Project/Area Number |
17K09843
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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 |
Metabolomics
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| Research Institution | International University of Health and Welfare |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 膵β細胞 / 糖尿病 / インスリン / 発生・分化 / 脱分化 / 成熟分化 / 発現制御 / 転写因子 / 遺伝子 / 老化 |
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| Outline of Final Research Achievements |
Dysfunction of insulin-secreting pancreatic β-cells causes diabetes. Recent studies reveal that loss of β-cell identity results in β-cell failure. In this study, comprehensive gene expression analyses were performed to compare 1) mature and immature islets of pancreas, 2) mature β-cells and other islet cells, 3) islets of diabetes and control mice by RNA-seq and microarray to clarify genes critical for β-cell identity. Although novel "master genes" important for maintenance of β-cells were not identified, these analyses uncovered genes and signaling pathways specifically repressed in mature pancreatic β-cells. Most of these genes are upregulated in diabetic islets. Activation in the expression of these genes in diabetes is caused by upregulation of several transcription factors, which can result in specific cellular events involved in dysfunction of β-cells. Our results suggest novel mechanism that can impair β-cell function, which may be involved in pathology of diabetes.
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| Academic Significance and Societal Importance of the Research Achievements |
これまで、膵β細胞特異的な機能の分子メカニズムについては、膵β細胞特異的に発現する分子の重要性が強調されてきた。そして病態メカニズムについては、それら分子の発現低下や消失が機能に与える影響を中心に、解析されてきた。これに対して本研究では、膵β細胞障害のメカニズムに、成熟膵β細胞で特異的に発現が抑制されている分子が重要である可能性を明らかにした。本研究により同定された新規遺伝子は、膵β細胞障害と糖尿病発症の分子メカニズムに重要であり、糖尿病の病態を反映する分子マーカーや新規治療開発の分子標的となり得る可能性が示唆されたことが、本研究成果の意義と考えられる。
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Report
(6 results)
Research Products
(56 results)
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[Journal Article] Islet cell dedifferentiation is a pathologic mechanism of long-standing progression of type 2 diabetes.2021
Author(s)
Amo-Shiinoki K, Tanabe K, Hoshii Y, Matsui H, Harano R, Fukuda T, Takeuchi T, Bouchi R, Takagi T, Hatanaka M, Takeda K, Okuya S, Nishimura W, Kudo A, Tanaka S, Tanabe M, Akashi T, Yamada T, Ogawa Y, Ikeda E, Nagano H, Tanizawa Y.
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Journal Title
JCI Insight
Volume: 6
Issue: 1
Pages: 143791-143791
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] 内臓脂肪組織の脂肪細胞と中皮細胞における転写因子Gata5の機能解析.2021
Author(s)
宇田川陽秀, 舟橋伸昭, 中野堅太, 柳田圭介, 岡村匡史, 添田光太郎, 南茂隆生, 平本正樹, 西村渉, 進藤英雄, 今泉美佳, 植木浩二郎, 安田和基.
Organizer
第64回日本糖尿病学会年次学術集会.
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[Presentation] ヒトの糖尿病においてβ細胞脱分化はβ細胞不全に関連する.2017
Author(s)
椎木幾久子, 田部勝也, 幡中雅行, 近藤 学, 西村 渉, 木村徳広, 池田栄二, 水上浩哉, 佐藤吉彦, 駒津光久, 谷澤幸生.
Organizer
第60回日本糖尿病学会年次学術集会.
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