Study on the regulation of lipid signaling in pancreatic β-cells and the pathogenesis of diabetes mellitus
Project/Area Number |
21790154
|
Research Category |
Grant-in-Aid for Young Scientists (B)
|
Allocation Type | Single-year Grants |
Research Field |
Medical pharmacy
|
Research Institution | University of Shizuoka |
Principal Investigator |
KANEKO Yukiko 静岡県立大学, 薬学部, 助教 (00381038)
|
Project Period (FY) |
2009 – 2012
|
Project Status |
Completed (Fiscal Year 2012)
|
Budget Amount *help |
¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2010: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2009: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
|
Keywords | 糖尿病 / ジアシルグリセロールキナーゼ / ジアシルグリセロール / インスリン分泌 / 膵β細胞 / プロテインキナーゼC / ホスファチジン酸 / プロテインキナーゼC |
Research Abstract |
Diacylglycerol kinases (DGK) phosphorylate diacylglycerol (DAG) to phosphatidic acid and strictly regulate the intracellular level of these lipid molecules. The expression of type I DGK (DGKαand γ) was detected in mouse pancreatic islets and the β-cell line MIN6. A specific type I DGK inhibitor inhibited insulin secretions and Ca2+concentration ([Ca2+]i) in MIN6 cells. Moreover, DGKαand γdoubleknockdown by siRNA led to significant decreases in insulin secretions. A membrane permeable DAG analog also inhibited [Ca2+]ielevations in MIN6 cells. These results suggest that DGKαand γare present in β-cells, and that DAG accumulation in β-cells resulting from hypofunction of these DGK isoforms leads to a decrease in [Ca2+]i,thereby reducing insulin secretion. Type I DGK could be a novel therapeutic target for diabetes mellitus.
|
Report
(4 results)
Research Products
(38 results)