The DOI matches its Crossref record; 39 of the 39 references it cites were found in a registry or an index.
GLP-1 Inhibits and Adrenaline Stimulates Glucagon Release by Differential Modulation of N- and L-Type Ca2+ Channel-Dependent Exocytosis
Open accessAbstract
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).
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“GLP-1 can directly bind to the receptors on the surface of α-cells in the pancreas, inhibiting the secretion of glucagon from these cells.234,235”
From Glucagon-like peptide-1 receptor: mechanisms and advances in therapy (2024) · cites this paper as [235]
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Citations
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Self-citationMolecular Mechanism Underlying the Intra-Islet Regulation of Glucagon Secretion
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Metadata
- Authors
- De Marinis, Y. Z., Salehi, A., Ward, C. E., Zhang, Q., Abdulkader, F., Bengtsson, M., Braha, O., Braun, M., Ramracheya, R., Amisten, S., Habib, A. M., Moritoh, Y., Zhang, E., Reimann, F., Rosengren, A. H., Shibasaki, T., Gribble, F., Renström, E., Seino, S., Eliasson, L., & Rorsman, P.
- Affiliations
- Lund University (SE)
- Churchill Hospital (GB)
- Universidade de São Paulo (BR)
- University of Cambridge (GB)
- Kobe University (JP)
- Corresponding author
- Eliasson, Lena
- ORCID
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2010-06
- Volume
- 11
- Issue
- 6
- Pages
- 543-553
- ISSN
- 1550-4131 (ISSN-L)
- PMC
- PMC4310935
- OpenAlex
- W2041346929
- Cited by
- 257
- References
- 39
- Citations by year
- 2026: 9 · 2025: 7 · 2024: 16 · 2023: 10 · 2022: 8 · 2021: 16 · 2020: 19 · 2019: 13 · 2018: 26 · 2017: 21 · 2016: 18 · 2015: 20 · 2014: 31 · 2013: 11 · 2012: 12
- FWCI
- 14.53
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Scientific Electronic Library Online (São Paulo Research Foundation, Latin American and Caribbean Center on Health Sciences Information, Conselho Nacional de Desenvolvimento Científico e Tecnológico) (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Lund University Publications (Lund University) (submittedVersion, other-oa)
- Funders
- Wellcome Trust (088357, 084210)
- Novo Nordisk Fonden (NNF10OC1013350)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Keywords
- glucagon secretion, glucagon-like peptide-1, epinephrine, alpha cells, N-type calcium channels, L-type calcium channels, exocytosis, protein kinase A, Epac2, cAMP signaling, pancreatic islets, GLP-1 receptor
- MeSH terms
- Cyclic AMP, Animals, Carrier Proteins, Cells, Cultured, Epinephrine, Exocytosis, Colforsin, Glucagon, Islets of Langerhans, Membrane Potentials, Mice, Inbred C57BL, Cyclic AMP-Dependent Protein Kinases, Guanine Nucleotide Exchange Factors, Calcium Channels, L-Type, Calcium Channels, N-Type, Mice, Glucagon-Like Peptide 1
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