Study on the regulation of lipid signaling in pancreatic β-cells and the pathogenesis of diabetes mellitus

二酰基甘油激酶（DGK）将二酰基甘油（DAG）磷酸化为磷脂酸，并严格调节细胞内这些脂质分子的水平。在小鼠胰岛和β细胞系MIN6中检测I型DGK （DGKα和γ）的表达。一种特殊的I型DGK抑制剂抑制MIN6细胞的胰岛素分泌和Ca2+浓度（[Ca2+] I）。此外，siRNA双敲低dgk α和γ导致胰岛素分泌明显减少。膜透性DAG类似物也抑制MIN6细胞中的[Ca2+]升高。这些结果表明，DGKα和γ存在于β-细胞中，而这些DGK亚型功能低下导致的DAG在β-细胞中的积累导致[Ca2+]i减少，从而减少胰岛素分泌。1型DGK可能成为治疗糖尿病的新靶点。

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.