Take Me To Your Leader": An Electrophysiological Appraisal of the Role of Hub Cells in Pancreatic Islets.

The coordinated electrical activity of beta-cells within the pancreatic islet drives oscillatory insulin secretion. A recent hypothesis postulates that specially equipped "hub" or "leader" cells within the beta-cell network drive islet oscillations and that electrically silencing or optically ablating these cells suppresses coordinated electrical activity (and thus insulin secretion) in the rest of the islet. In this Perspective, we discuss this hypothesis in relation to established principles of electrophysiological theory. We conclude that whereas electrical coupling between beta-cells is sufficient for the propagation of excitation across the islet, there is no obvious electrophysiological mechanism that explains how hyperpolarizing a hub cell results in widespread inhibition of islet electrical activity and disruption of their coordination. Thus, intraislet diffusible factors should perhaps be considered as an alternate mechanism.