Regulation of insulin granule exocytosis

Abstract

Insulin is stored in secretory granules within the pancreatic beta cell. The release of insulin requires the fusion of the secretory granule with the plasma membrane and the discharge of the granule contents into the extracellular space. Insulin secretion follows a characteristic biphasic time course consisting of a rapid but transient 1st phase followed by a slowly developing and sustained 2nd phase. Because type 2 diabetes involves defects of insulin secretion, manifested as a loss of 1st phase and a reduction of the 2nd phase, it is important to understand the cellular mechanisms underlying biphasic insulin secretion. Here we describe how glucose, via electrical activity, triggers insulin secretion. With this background, we consider the molecular machinery involved in the exocytosis of insulin, the possibility that Ca 2+-influx through different Ca2+ channels underlies phasic insulin secretion, how Ca2+ is sensed by the beta-cell granules, the maintenance of the pool of release-competent granules by intracellular granule trafficking and glucose metabolism, the existence of two parallel pathways of exocytosis in the beta cell, and finally the evidence suggesting that exocytosis is not an all-or-none event and that significant regulation of beta-cell secretion occurs at the levels of the fusion pore (the connection between the granule interior and the extracellular space). © 2008 Springer.