Physiology of pancreatic β-cells: Ion channels and molecular mechanisms implicated in stimulus-secretion coupling.

Abstract

The human and mouse islet of Langerhans is an endocrine organ composed of five different cells types; insulin-secreting β-cells, glucagon-producing α-cells, somatostatin-producing δ-cells, pancreatic polypeptide-secreting PP cells and ɛ-cells that secretes ghrelin. The most important cells are the pancreatic β-cells that comprise around 45-50% of human islets and 75-80% in the mouse. Pancreatic β-cells secrete insulin at high glucose concentration, thereby finely regulating glycaemia by the hypoglycaemic effects of this hormone. Different ion channels are implicated in the stimulus-secretion coupling of insulin. An increase in the intracellular ATP concentration leads to closure KATP channels, depolarizing the cell and opening voltage-gated calcium channels. The increase of intracellular calcium concentration induced by calcium entry through voltage-gated calcium channels promotes insulin secretion. Here, we briefly describe the diversity of ion channels present in pancreatic β-cells and the different mechanisms that are responsible to induce insulin secretion in human and mouse cells. Moreover, we described the pathophysiology due to alterations in the physiology of the main ion channels present in pancreatic β-cell and its implication to predispose metabolic disorders as type 2 diabetes mellitus.