| Literature DB >> 20519125 |
Yang Z De Marinis1, Albert Salehi1, Caroline E Ward2, Quan Zhang2, Fernando Abdulkader2,3, Martin Bengtsson2, Orit Braha2, Matthias Braun2, Reshma Ramracheya2, Stefan Amisten2, Abdella M Habib4, Yusuke Moritoh2, Enming Zhang1, Frank Reimann4, Anders Rosengren1, Tadao Shibasaki5, Fiona Gribble4, Erik Renström1, Susumu Seino5, Lena Eliasson1, Patrik Rorsman2.
Abstract
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). Copyright 2010 Elsevier Inc. All rights reserved.Entities:
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Year: 2010 PMID： 20519125 PMCID： PMC4310935 DOI： 10.1016/j.cmet.2010.04.007
Source DB: PubMed Journal: Cell Metab ISSN： 1550-4131 Impact factor: 27.287