AMPA Receptors Regulate Exocytosis and Insulin Release in Pancreatic β Cells

Ionotropic glutamate receptors ( iGluRs ) are expressed in islets and insulinoma cells and involved in insulin secretion. However, the exact roles that iGluRs play in β cells remain unclear. Here, we demonstrated that GluR2 ‐containing α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid receptors ( AMPARs ) were expressed in mouse β cells. Glutamate application increased both cytosolic calcium and the number of docked insulin‐containing granules, which resulted in augmentation of depolarization‐induced exocytosis and high‐glucose‐stimulated insulin release. While glutamate application directly depolarized β cells, it also induced an enormous depolarization when K ATP channels were available. Glutamate application reduced the conductance of K ATP channels and increased voltage oscillations. Moreover, actions of AMPARs were absent in Kir 6.2 knock‐out mice. The effects of AMPARs on K ATP channels were mediated by cytosolic cGMP . Taken together, our experiments uncovered a novel mechanism by which AMPARs participate in insulin release.