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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1626405
- author
- 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. (More)
- De Marinis, Yang
LU
; Salehi, S Albert
LU
; Ward, Caroline E
; Zhang, Quan
LU
; Abdulkader, Fernando
; Bengtsson, Martin
; Braha, Orit
; Braun, Matthias
; Ramracheya, Reshma
; Amisten, Stefan
LU
; Habib, Abdella M
; Moritoh, Yusuke
; Zhang, Enming
LU
; Reimann, Frank
; Rosengren, Anders
LU
; Shibasaki, Tadao
; Gribble, Fiona
; Renström, Erik
LU
; Seino, Susumu
; Eliasson, Lena
LU
and Rorsman, Patrik
(Less)
- organization
- publishing date
- 2010
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Cell Metabolism
- volume
- 11
- issue
- 6
- pages
- 543 - 553
- publisher
- Cell Press
- external identifiers
-
- wos:000278747800012
- pmid:20519125
- scopus:77956399106
- pmid:20519125
- 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
- 2016-04-04 08:10:14
- date last changed
- 2022-04-15 19:47:13
@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 <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 = {{https://lup.lub.lu.se/search/files/5168442/1659374.pdf}},
doi = {{10.1016/j.cmet.2010.04.007}},
volume = {{11}},
year = {{2010}},
}