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 β-cells and the capillary bed of islets of Langerhans in both mouse and human. Integrins are exclusively activated at the region where β-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 β-cells forms a specialised domain that is analogous to the presynaptic active zone of neurones. Pancreatic β-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 β-cells and some have also been shown to control insulin secretion. We present a model that suggests this active zone-like domain in β-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.