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

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 beta-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 beta-cells express ion channels whose physio/pathological role is underappreciated. Here, we describe the mitochondrial ion channels identified in pancreatic beta-cells, we further discuss the possibility of targeting specific beta-cell mitochondrial channels for the treatment of Type 2 diabetes, and we finally highlight the evidence from clinical studies.

Automated summary

Pancreatic beta-cells play a central role in regulating glucose homeostasis, with mitochondria playing a crucial role in linking nutrient metabolism to insulin secretion. Mitochondria, as double-membrane organelles with various channels, regulate energy production, signaling, and cell death within beta-cells.