Dual effect of reduced type I diacylglycerol kinase activity on insulin secretion from MIN6 β-cells.

The role of type I diacylglycerol kinases (DGKs) in the regulation of insulin secretion was investigated in MIN6 β-cells. In intracellular Ca concentration ([Ca]) measurement experiments, 1 μM R59949, a type I DGK inhibitor, and 10 μM DiC, a diacylglycerol (DAG) analog, amplified 22.2 mM glucose-induced [Ca] oscillations in a protein kinase C (PKC)-dependent manner, whereas 10 μM R59949 and 100 μM DiC decreased [Ca] independent of PKC. High concentrations of R59949 and DiC attenuated voltage-dependent Ca channel currents. According to these results, 22.2 mM glucose-stimulated insulin secretion (GSIS) was potentiated by 1 μM R59949 but suppressed by 10 μM of the same. The DGKα inhibitor R59022 showed a similar dual effect. Conversely, DiC at 10 and 100 μM potentiated GSIS, although 100 μM DiC decreased [Ca]. These results suggest that DAG accumulated through declined type I DGK activity shows a dual effect on insulin secretion depending on the degree of accumulation; a mild DAG accumulation induces a PKC-dependent stimulatory effect on insulin secretion, whereas an excessive DAG accumulation suppresses it in a PKC-independent manner, possibly via attenuation of VDCC activity.