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
Cites
Hypoglycaemia: the limiting factor in the glycaemic management of type I and type II diabetes.
Cryer, P. (2002) · Diabetologia · doi:10.1007/s00125-002-0822-9 · Cited by 794 · cited 6×
“This would explain why impaired counterregulation is often seen in diabetic patients (Cryer, 2002).”
BackgroundInfluentialGlucose Sensing in L Cells: A Primary Cell Study
Reimann, F., Habib, A. M., Tolhurst, G., Parker, H. E., Rogers, G. J., & Gribble, F. M. (2008) · Cell Metabolism · doi:10.1016/j.cmet.2008.11.002 · Cited by 733 · cited 4×
“GIP, GLP-1, and b-Adrenoreceptor Densities in Mouse a and b Cells Pure a and b cell fractions were obtained by FACS of dispersed islets from mice expressing YFP under the proglucagon promoter (Reimann et al., 2008).”
BackgroundMethodInfluentialSelf-citationA novel Epac-specific cAMP analogue demonstrates independent regulation of Rap1 and ERK
Enserink, J. M., Christensen, A. E., de Rooij, J., van Triest, M., Schwede, F., Genieser, H. G., Døskeland, S. O., Blank, J. L., & Bos, J. L. (2002) · Nature Cell Biology · doi:10.1038/ncb874 · Cited by 625 · cited 2×
“Involvement of Epac2 in the Stimulation of Exocytosis The effects of forskolin and adrenaline on a cell exocytosis were mimicked by intracellular application of 100 mM 8CPT-2MecAMP, a selective agonist of the low-affinity cAMP sensor Epac2 (Enserink et al., 2002).”
Methodα-Cells of the Endocrine Pancreas: 35 Years of Research but the Enigma Remains
Gromada, J., Franklin, I., & Wollheim, C. B. (2007) · Endocrine Reviews · doi:10.1210/er.2006-0007 · Cited by 596
Miki, T., Liss, B., Minami, K., Shiuchi, T., Saraya, A., Kashima, Y., Horiuchi, M., Ashcroft, F. M., Minokoshi, Y., Roeper, J., et al. (2001) · Nature Neuroscience · doi:10.1038/87455 · Cited by 519 · cited 2×
“Glucagon secretion is also under tight neuronal and hormonal control (Miki et al., 2001).”
BackgroundSelf-citationEssential role of Epac2/Rap1 signaling in regulation of insulin granule dynamics by cAMP
Shibasaki, T., Takahashi, H., Miki, T., Sunaga, Y., Matsumura, K., Yamanaka, M., Zhang, C., Tamamoto, A., Satoh, T., Miyazaki, J.-I., et al. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0707054104 · Cited by 425 · cited 5×
“As the effects of the higher concentrations of cAMP or forskolin are resistant to pharmacological inhibition of PKA, it seems likely that they are mediated by activation of the low-affinity cAMP-sensor Epac2 (Shibasaki et al., 2007).”
BackgroundMethodInfluentialSelf-citationGenetically lean mice result from targeted disruption of the RIIβ subunit of protein kinase A
Cummings, D. E., Brandon, E. P., Planas, J. V., Motamed, K., Idzerda, R. L., & McKnight, G. S. (1996) · Nature · doi:10.1038/382622a0 · Cited by 420 · cited 5×
“PKA regulatory subunit type 1 (PKA-RI) and type 2 (PKA-RII) immunoreactivity was detected in mouse a cells cultured overnight on glass coverslips, fixed with 4% paraformaldehyde in PBS for 1 hr, and permeabilized with 5% Triton X-100 overnight.”
BackgroundInfluentialBraun, M., Ramracheya, R., Bengtsson, M., Zhang, Q., Karanauskaite, J., Partridge, C., Johnson, P. R., & Rorsman, P. (2008) · Diabetes · doi:10.2337/db07-0991 · Cited by 417 · cited 1×
“The validity of this method was confirmed by immunostaining as previously described (Braun et al., 2008).”
MethodSelf-citationGlucagon physiology and pathophysiology in the light of new advances
Unger, R. H. (1985) · Diabetologia · doi:10.1007/bf00281991 · Cited by 361 · cited 2×
“In both type 1 and type 2 diabetes, hyper- glycaemia results from a combination of insufficient insulin secretion and oversecretion of glucagon (Dunning et al., 2005; Unger, 1985).”
BackgroundInterplay of Nutrients and Hormones in the Regulation of Insulin Release*
PIPELEERS, D. G., Schuit, F. C., Veld, P. I. '., Maes, E., Hooghe-Peters, E. L., Winkel, M. V. D., & Gepts, W. (1985) · Endocrinology · doi:10.1210/endo-117-3-824 · Cited by 357 · cited 1×
“GLP-1 inhibits glucagon secretion, whereas GIP and adrenaline stimu- late its release (de Heer et al., 2008; Pipeleers et al., 1985).”
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Sorted by citations
Glucagon-like peptide 1 (GLP-1)
Müller, T. D., Finan, B., Bloom, S. R., D'Alessio, D., Drucker, D. J., Flatt, P. R., Fritsche, A., Gribble, F., Grill, H. J., Habener, J. F., et al. (2019) · Molecular Metabolism · doi:10.1016/j.molmet.2019.09.010 · Cited by 1,868
Self-citationGlucagon-like peptide-1 receptor: mechanisms and advances in therapy
Zheng, Z., Zong, Y., Ma, Y., Tian, Y., Pang, Y., Zhang, C., & Gao, J. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01931-z · Cited by 1,036
Enteroendocrine Cells: Chemosensors in the Intestinal Epithelium
Gribble, F. M., & Reimann, F. (2016) · Annual Review of Physiology · doi:10.1146/annurev-physiol-021115-105439 · Cited by 683
Self-citationDayeh, T., Volkov, P., Salö, S., Hall, E., Nilsson, E., Olsson, A. H., Kirkpatrick, C. L., Wollheim, C. B., Eliasson, L., Rönn, T., et al. (2014) · PLoS Genetics · doi:10.1371/journal.pgen.1004160 · Cited by 523
Self-citationPhysiology of Proglucagon Peptides: Role of Glucagon and GLP-1 in Health and Disease
Sandoval, D. A., & D'Alessio, D. A. (2015) · Physiological Reviews · doi:10.1152/physrev.00013.2014 · Cited by 498
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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