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, signaling, 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.