Mitochondrial ion channels in pancreatic β-cells: Novel pharmacological targets for the treatment of Type 2 diabetes.

Abstract

Pancreatic beta‐cells are central regulators of glucose homeostasis. By tightly coupling nutrient sensing and granule exocytosis, beta‐cells adjust the secretion of insulin to the circulating blood glucose levels. Failure of beta‐cells to augment insulin secretion in insulin‐resistant individuals leads progressively to impaired glucose tolerance, Type 2 diabetes, and diabetes‐related diseases. Mitochondria play a crucial role in β‐cells during nutrient stimulation, linking the metabolism of glucose and other secretagogues to the generation of signals that promote insulin secretion. Mitochondria are double‐membrane organelles containing numerous channels allowing the transport of ions across both membranes. These channels regulate mitochondrial energy production, signalling, and cell death. The mitochondria of β‐cells express ion channels whose physio/pathological role is underappreciated. Here, we describe the mitochondrial ion channels identified in pancreatic β‐cells, we further discuss the possibility of targeting specific β‐cell mitochondrial channels for the treatment of Type 2 diabetes, and we finally highlight the evidence from clinical studies.LINKED ARTICLESThis article is part of a themed issue on Cellular metabolism and diseases. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.10/issuetoc