Bidirectional granule turnover in the submembrane space during K+ depolarization-induced secretion

Background and aims: The release of a pool of membrane-adjacent secretory granules which are in a primed and docked state and await one final trigger, a depolarization-induced influx of Ca2+, is held responsible for the first phase of glucose-induced insulin secretion. A number of recent observations has put this hypothesis into question. Methods: Insulin secretion was measured by perifusion of mouse islets and MIN6 pseudo-islets and ELISA of the fractionated effluate. The free cytosolic Ca2+ concentration ([Ca2+]i) of islets and MIN6 cells was measured with the Fura technique. Granules in the immediate vicinity…