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The secretion of glucagon by pancreatic alpha-cells plays a critical role in the regulation of glycaemia. This hormone counteracts hypoglycaemia and opposes insulin actions by stimulating hepatic glucose synthesis and mobilization, thereby increasing blood glucose concentrations. During the last decade, knowledge of alpha-cell physiology has greatly improved, especially concerning molecular and cellular mechanisms. In this review, we have addressed recent findings on alpha-cell physiology and the regulation of ion channels, electrical activity, calcium signals and glucagon release. Our focus in this review has been the multiple control levels that modulate glucagon secretion from glucose and nutrients to paracrine and neural inputs. Additionally, we have described the glucagon actions on glycaemia and energy metabolism, and discussed their involvement in the pathophysiology of diabetes. Finally, some of the present approaches for diabetes therapy related to alpha-cell function are also discussed in this review. A better understanding of the alpha-cell physiology is necessary for an integral comprehension of the regulation of glucose homeostasis and the development of diabetes.

Physiology of the pancreatic α-cell and glucagon secretion: role in glucose homeostasis and diabetes