Pancreatic ?-Cell Electrical Activity and Insulin Secretion: Of Mice and Men.

ABSTRACT: The pancreatic ?-cell plays a key role in glucose homeostasis by secreting insulin, the only hormone capable of lowering the blood glucose concentration. Impaired insulin secretion results in the chronic hyperglycemia that characterizes type 2 diabetes (T2DM), which currently afflicts >450 million people worldwide. The healthy ?-cell acts as a glucose sensor matching its output to the circulating glucose concentration. It does so via metabolically induced changes in electrical activity, which culminate in an increase in the cytoplasmic Ca2+ concentration and initiation of Ca2+-dependent exocytosis of insulin-containing secretory granules. Here, we review recent advances in our understanding of the ?-cell transcriptome, electrical activity, and insulin exocytosis. We highlight salient differences between mouse and human ?-cells, provide models of how the different ion channels contribute to their electrical activity and insulin secretion, and conclude by discussing how these processes become perturbed in T2DM.

SUBMITTER: Rorsman P 

PROVIDER: S-EPMC5866358 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature