TRPM2 modulates insulin secretion in pancreatic β-cells

Abstract

Insulin secretion from pancreatic β-cells is the primary mechanism by which the body lowers blood glucose concentrations. Glucose is the principal stimulator of insulin secretion, and the primary pathway involved in glucose-stimulated insulin secretion is the ATP-sensitive K+ channel voltage-gated Ca2+ channel-mediated pathway. Several TRP channels expressed in pancreatic β-cells have been reported to be involved in insulin secretion. One recent report found that TRPM2 is expressed in pancreatic β-cells and modulates insulin secretion stimulated by glucose and further potentiated by incretin hormones. TRPM2 is a Ca2+-permeable non-selective cation channel activated by adenosine dinucleotides, hydrogen peroxide, and intracellular Ca2+. Glucose tolerance was impaired and insulin secretion was decreased in TRPM2 knockout mice. Insulin secretion via TRPM2 occurs not only through control of intracellular Ca2+ concentrations but also through Ca2+ influx-independent mechanisms. Although further examination is needed to clarify the mechanism of TRPM2-mediated insulin secretion, TRPM2 may be a key player in regulation of insulin secretion and could represent a new target for diabetes therapy.