Intracellular lipid signaling analysis for the development of novel diabetes therapeutic agents targeting neogenesis and proliferation of pancreatic beta-cells
Project/Area Number |
17H02175
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Applied health science
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Research Institution | University of Shizuoka |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
金子 雪子 静岡県立大学, 薬学部, 講師 (00381038)
白井 康仁 神戸大学, 農学研究科, 教授 (60263399)
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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 |
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2019: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2018: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2017: ¥10,400,000 (Direct Cost: ¥8,000,000、Indirect Cost: ¥2,400,000)
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Keywords | 糖尿病 / β細胞 / ジアシルグリセロールキナーゼ / ジアシルグリセロール / 増殖 / β 細胞 / 新生 / インスリン / 膵β細胞量 |
Outline of Final Research Achievements |
Our previous study showed that an increased number of small islets was observed in the pancreas of β-cell-specific diacylglycerol kinase δ (DGKδ) knockout (βDGKδ KO) mice. Based on these findings, we investigated the mechanism for the increase in β-cell mass due to DGKδ deficiency and the possibility whether the suppression of DGKδ improves hyperglycemia. We found that that DGKδ knockdown in MIN6 β-cells showed a significant increase in proliferation, accompanied with an increased expression of cell-cycle related genes. In addition, we confirmed that streptozotocin-induced hyperglycemia and β-cell loss were alleviated in βDGKδ KO mice. These results suggest that the suppression of DGKδ in β-cells leads to an increased β-cell mass via proliferation, thereby improving hyperglycemia.
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Academic Significance and Societal Importance of the Research Achievements |
1型糖尿病のみならず2型糖尿病においても、膵β細胞量が減少し病態を悪化させることが知られている。しかしながら、β細胞量を回復させる治療薬は未だ存在せず、糖尿病根本治療の重要なターゲットと考えられている。本研究ではマウスでの検討により、生理活性脂質ジアシルグリセロール (DAG) の代謝酵素の一つであるDGK δのβ細胞における機能を抑制すると、β細胞の増殖が亢進してβ細胞量が増加し、血糖上昇が緩和されることを示した。すなわち、DGK δの新たな糖尿病治療薬のターゲットとしての可能性を示した。
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Report
(4 results)
Research Products
(63 results)
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[Journal Article] DgMab-6: Antihuman DGKgamma Monoclonal Antibody for Immunocytochemistry.2018
Author(s)
Nakano T, Ogasawara S, Tanaka T, Hozumi Y, Yamaki A, Sakane F, Shirai Y, Nakamura T, Yanaka M, Yamada S, Kaneko MK, Kato Y, Goto K.
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Journal Title
Monoclonal Antibodies in Immunodiagnosis and Immunotherapy
Volume: 37
Issue: 5
Pages: 229-232
DOI
Related Report
Peer Reviewed
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