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

Abstract

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 β-cells are the only cells that can lower blood glucose levels by secreting insulin. Therefore, maintaining insulin-secreting β-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 β-cell apoptosis, and the increase in β-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 β-cell death. In addition, we have elucidated the function of DGKδ as a suppressor of β-cell proliferation. This review introduces the findings of our study leading to development of novel anti-diabetic therapeutics that targets pancreatic β-cells.

Oleic Acid Activates Mitochondrial Energy Metabolism and Reduces Oxidative Stress Resistance in the Pancreatic β-Cell Line INS-1

“…Type 2 diabetes mellitus is a disease with diverse pathological conditions, and dysfunction of insulin secretion from pancreatic β-cells is a condition seen in about half of all Japanese patients with type 2 diabetes mellitus. [1][2][3] It is known that the pancreatic β-cells are adversely affected by increased free fatty acid (FFA) concentrations in the blood, due to obesity and other causes. 4,5) In particular, the adverse effects of saturated fatty acids (SFAs) on pancreatic β-cells are significant and varied, and include suppression of insulin secretion 6) and elevated nitric oxide (NO) levels.…”