Development of Therapeutic Agents with a Novel Mechanism of Action Targeting Pancreatic β-Cells for Diabetes

Although diabetes is associated with an increased risk of various diseases, including cancer and infectious diseases, no definitive cure has yet been found. Long-term treatment for blood glucose control significantly reduces the QOL. Pancreatic beta-cells are the only cells that can lower blood glucose levels by secreting insulin. Therefore, maintaining insulin-secreting beta-cells is crucial in preventing the progression of diabetes and improving the QOL. We have investigated the mechanisms for the regulation of insulin secretion, the prevention of beta-cell apoptosis, and the increase in beta-cell mass. In particular, we have elucidated the involvement of type I diacylglycerol kinase (DGK) in the regulation of insulin secretion and the effects of nitric oxide (NO) signaling and natural products in suppressing beta-cell death. In addition, we have elucidated the function of DGKd as a suppressor of beta-cell proliferation. This review introduces the findings of our study leading to development of novel anti-diabetic therapeutics that targets pancreatic beta-cells.