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GLP-1 inhibits and adrenaline stimulates glucagon release by differential modulation of N- and L-type Ca2+ channel-dependent exocytosis.

De Marinis, Yang LU ; Salehi, S Albert LU ; Ward, Caroline E; Zhang, Quan LU ; Abdulkader, Fernando; Bengtsson, Martin; Braha, Orit; Braun, Matthias; Ramracheya, Reshma and Amisten, Stefan LU , et al. (2010) In Cell Metabolism 11(6). p.543-553
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... (More)
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). (Less)
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Contribution to journal
publication status
published
subject
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Cell Metabolism
volume
11
issue
6
pages
543 - 553
publisher
Cell Press
external identifiers
  • wos:000278747800012
  • pmid:20519125
  • scopus:77956399106
ISSN
1550-4131
DOI
10.1016/j.cmet.2010.04.007
language
English
LU publication?
yes
id
5e324205-820c-49b6-bf85-11290b37574a (old id 1626405)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/20519125?dopt=Abstract
date added to LUP
2010-07-05 09:15:31
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2018-06-24 04:47:21
@article{5e324205-820c-49b6-bf85-11290b37574a,
  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 &lt;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).},
  author       = {De Marinis, Yang and Salehi, S Albert and Ward, Caroline E and Zhang, Quan and Abdulkader, Fernando and Bengtsson, Martin and Braha, Orit and Braun, Matthias and Ramracheya, Reshma and Amisten, Stefan and Habib, Abdella M and Moritoh, Yusuke and Zhang, Enming and Reimann, Frank and Rosengren, Anders and Shibasaki, Tadao and Gribble, Fiona and Renström, Erik and Seino, Susumu and Eliasson, Lena and Rorsman, Patrik},
  issn         = {1550-4131},
  language     = {eng},
  number       = {6},
  pages        = {543--553},
  publisher    = {Cell Press},
  series       = {Cell Metabolism},
  title        = {GLP-1 inhibits and adrenaline stimulates glucagon release by differential modulation of N- and L-type Ca2+ channel-dependent exocytosis.},
  url          = {http://dx.doi.org/10.1016/j.cmet.2010.04.007},
  volume       = {11},
  year         = {2010},
}