Gap junctions and other mechanisms of cell–cell communication regulate basal insulin secretion in the pancreatic islet

Non-technical summary The islet of Langerhans secretes the hormone insulin in response to elevated glucose. Interactions between cells within the islet is important for the regulation of insulin secretion, to both suppress basal insulin secretion and enhance the glucose-stimulated response. We show that multiple mechanisms of cell–cell communication are required for the suppression of basal insulin release. First, gap junctions suppress spontaneous calcium signals which suppresses triggering of insulin release. Second, other juxtacrine mechanisms, regulated by cAMP and glucose, suppress more distal steps in the regulation of insulin granule exocytosis. Each mechanism is sufficiently robust to compensate for a loss of the other and still fully suppress basal insulin release. This new insight into the function of islet of Langerhans is important for understanding the development and treatment of diabetes.