β-Cell glutamate signaling: Its role in incretin-induced insulin secretion

Insulin secretion from the pancreatic β-cell (referred to as β-cell hereafter) plays a central role in glucose homeostasis. Impaired insulin secretion is a major factor contributing to the development of diabetes and, therefore, is an important target for treatment of the disease. Cyclic adenosine monophosphate is a key second messenger in β-cells that amplifies insulin secretion. Incretins released by the gut potentiate insulin secretion through cyclic adenosine monophosphate signaling in β-cells, which is the basis for the incretin-based diabetes therapies now being used worldwide. Despite its importance, the interaction between glucose metabolism and incretin/cyclic adenosine monophosphate signaling in β-cells has long been unknown. A recent study showed that cytosolic glutamate produced by glucose metabolism in β-cells is a key signal in incretin-induced insulin secretion. Here we review the physiological and pathophysiological roles of β-cell glutamate signaling in incretin-induced insulin secretion.