2012 Fiscal Year Final Research Report
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
|
| 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 |
|---|
| 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.
|
