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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 muM) concentrations of forskolin, respectively. The expression of GLP-1 receptors in alpha cells is <0.2% of that in beta 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 alpha cell electrical activity but selectively inhibits N-type Ca(2+) channels and exocytosis. Adrenaline stimulates alpha cell electrical activity, increases [Ca(2+)](i), enhances L-type Ca(2+) 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 Ca(2+) channels via a small increase in intracellular cAMP ([cAMP](i)). Adrenaline stimulates L-type Ca(2+) channel-dependent exocytosis by activation of the low-affinity cAMP sensor Epac2 via a large increase in [cAMP](i).

Original publication

DOI

10.1016/j.cmet.2010.04.007

Type

Journal article

Journal

Cell Metab

Publication Date

09/06/2010

Volume

11

Pages

543 - 553

Keywords

Animals, Calcium Channels, L-Type, Calcium Channels, N-Type, Carrier Proteins, Cells, Cultured, Colforsin, Cyclic AMP, Cyclic AMP-Dependent Protein Kinases, Epinephrine, Exocytosis, Glucagon, Glucagon-Like Peptide 1, Guanine Nucleotide Exchange Factors, Islets of Langerhans, Membrane Potentials, Mice, Mice, Inbred C57BL