Cell Metabolism
Volume 11, Issue 6, 9 June 2010, Pages 543-553
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Article
GLP-1 Inhibits and Adrenaline Stimulates Glucagon Release by Differential Modulation of N- and L-Type Ca2+ Channel-Dependent Exocytosis

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Summary

Glucagon secretion is inhibited by glucagon-like peptide-1 (GLP-1) and stimulated by adrenaline. These opposing effects on glucagon secretion are mimicked by low (1–10 nM) and high (10 μM) concentrations of forskolin, respectively. The expression of GLP-1 receptors in α cells is <0.2% of that in β cells. The GLP-1-induced suppression of glucagon secretion is PKA dependent, is glucose independent, and does not involve paracrine effects mediated by insulin or somatostatin. GLP-1 is without much effect on α cell electrical activity but selectively inhibits N-type Ca2+ channels and exocytosis. Adrenaline stimulates α cell electrical activity, increases [Ca2+]i, enhances L-type Ca2+ channel activity, and accelerates exocytosis. The stimulatory effect is partially PKA independent and reduced in Epac2-deficient islets. We propose that GLP-1 inhibits glucagon secretion by PKA-dependent inhibition of the N-type Ca2+ channels via a small increase in intracellular cAMP ([cAMP]i). Adrenaline stimulates L-type Ca2+ channel-dependent exocytosis by activation of the low-affinity cAMP sensor Epac2 via a large increase in [cAMP]i.

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These authors contributed equally to this work