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Glucose controls glucagon secretion by directly modulating cAMP in alpha cells – published online 05/04/2019

Figure from Yu paper

Qian Yu, Hongyan Shuai, Parvin Ahooghalandari, Erik Gylfe, Anders Tengholm


Despite the importance of glucagon in glycaemic control, it remains unclear how glucose regulates glucagon secretion from pancreatic alpha cells. In this issue, Yu et al ( investigate the role of the intracellular messenger cAMP in alpha-cell-intrinsic glucose regulation of glucagon release. The authors report that glucose-induced alterations of glucagon release are paralleled by changes in subplasmalemmal cAMP concentration in alpha cells. In support of a regulatory role for cAMP, glucose-induced suppression of glucagon release was prevented by imposed elevations in cAMP, while inhibition of protein kinase A (a mediator of the effects of cAMP) mimicked the suppressive effect of glucose on glucagon. Yu and colleagues provide evidence that glucose acts directly on alpha cells to regulate glucagon secretion independent of paracrine signalling from insulin or somatostatin. The authors conclude that these findings point to a new mechanism for glucose control of glucagon release and indicate that the counter-regulatory glucagon response to hypoglycaemia could be enhanced by agents that increase cAMP concentration in alpha cells.

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