Plasma Membrane Phosphatidylinositol 4,5-Bisphosphate Regulates Ca(2+)-Influx and Insulin Secretion from Pancreatic β...

Insulin secretion from pancreatic β cells is regulated by the blood glucose concentration and occurs through Ca(2+)-triggered exocytosis. The activities of multiple ion channels in the β cell plasma membrane are required to fine-tune insulin secretion in order to maintain normoglycemia. Phosphoinositide lipids in the plasma membrane often gate ion channels, and variations in the concentration of these lipids affect ion-channel open probability and conductance. Using light-regulated synthesis or depletion of plasma membrane phosphatidylinositol 4,5-bisphosphate (PI[4,5]P2), we found that this lipid positively regulated both depolarization- and glucose-triggered Ca(2+) influx in a dose-dependent manner. Small reductions of PI(4,5)P2 caused by brief illumination resulted in partial suppression of Ca(2+) influx that followed the kinetics of the lipid, whereas depletion resulted in marked inhibition of both Ca(2+) influx and insulin secretion.