Diacylglycerol kinase ζ is a positive insulin secretion regulator in pancreatic β-cell line MIN6

Abstract

Some isoforms of diacylglycerol (DAG) kinase (DGK), an enzyme converting DAG into phosphatidic acid, i.e., DGKα, γ and δ, have been reportedly involved in the regulation of pancreatic β-cell function. DGKζ has also been reported to be expressed in rat pancreatic β-cells. However, its function in pancreatic β-cells remains unknown. The present study aimed to elucidate the function of DGKζ in pancreatic β-cells. The expression of DGKζ was detected in the β-cell line MIN6B and mouse pancreatic islets and in the cytoplasmic fraction from MIN6B cells. The knockdown of DGKζ with siRNA significantly decreased glucose-induced insulin secretion in MIN6B cells. The induction of DGKζ expression in MIN6CEon1 cells with a doxycycline-inducible stable expression system significantly increased glucose-induced insulin secretion. In contrast, glucose-induced insulin secretion was not changed when a kinase-dead DGKζ mutant (G356D) was overexpressed in MIN6CEon1 cells, indicating that a mechanism dependent on its kinase activity mediates the facilitatory effect of DGKζ on glucose-induced insulin secretion. Additionally, we revealed that DGKζ overexpression exhibited no effect on cell cycle of MIN6 cells. These results suggest that DGKζ plays a facilitatory role in insulin secretion in pancreatic β-cells.