Diacylglycerol kinase δ functions as a proliferation suppressor in pancreatic β-cells

Although an aberrant reduction in pancreatic beta-cell mass contributes to the pathogenesis of diabetes, the mechanism underlying the regulation of beta-cell mass is poorly understood. Here, we show that diacylglycerol kinase delta (DGK delta) is a key enzyme in the regulation of beta-cell mass. DGK delta expression was detected in the nucleus of beta-cells. We developed beta-cell-specific DGK delta knockout (beta DGK delta KO) mice, which showed lower blood glucose, higher plasma insulin levels, and better glucose tolerance compared to control mice. Moreover, an increased number of small islets and Ki-67-positive islet cells, as well as elevated cyclin B1 expression in the islets, were detected in the pancreas of beta DGK delta KO mice. DGK delta knockdown in the beta-cell line MIN6 induced significant increases in bromodeoxyuridine (BrdU) incorporation and cyclin B1 expression. Finally, we confirmed that streptozotocin-induced hyperglycemia and beta-cell loss were alleviated in beta DGK delta KO mice. Thus, suppressing the expression or enzymatic activity of DGK delta that functions as a suppressor of beta-cell proliferation could be a novel therapeutic approach to increase beta-cell mass for the treatment of diabetes.

Automated summary

The study revealed that DGK delta plays a key role in regulating beta-cell mass, with knockout resulting in improved insulin levels and glucose tolerance. Inhibiting DGK delta may be a novel therapeutic approach for increasing beta-cell mass in diabetes treatment.