Presynaptic-like mechanisms and the control of insulin secretion in pancreatic β-cells.

Exocytotic release of hormones from endocrine cells must encompass mechanisms that direct the hormone into the blood stream. Increasing evidence indicates an intimate link between pancreatic 13-cells and the capillary bed of islets of Langerhans in both mouse and human. Integrins are exclusively activated at the region where 13-cells contact extracellular matrix proteins that surround the islet capillaries; furthermore, insulin granule exocytosis is targeted to this same region, therefore delivering hormone directly into the blood stream.In this review we discuss evidence suggesting that the capillary interface of 13-cells forms a specialised domain that is analogous to the presynaptic active zone of neurones. Pancreatic 13-cells possess many of the same proteins as found in the neuronal active zone, including several key presynaptic scaffold proteins. These scaffold proteins are enriched at the capillary interface of 13-cells and some have also been shown to control insulin secretion. We present a model that suggests this active zone-like domain in 13-cells may anchor key components of the stimulus secretion cascade, to not only target granule exocytosis to this region but also function as a significant regulator of insulin secretion.