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
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“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).”
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BackgroundProtein Kinase A Type I and Type II Define Distinct Intracellular Signaling Compartments
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BackgroundVoltage‐gated and resting membrane currents recorded from B‐cells in intact mouse pancreatic islets
Göpel, S., Kanno, T., Barg, S., Galvanovskis, J., & Rorsman, P. (1999) · The Journal of Physiology · doi:10.1111/j.1469-7793.1999.00717.x · Cited by 226 · cited 1×
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MethodSelf-citationTight coupling between electrical activity and exocytosis in mouse glucagon-secreting alpha-cells.
Barg, S., Galvanovskis, J., Göpel, S. O., Rorsman, P., & Eliasson, L. (2000) · Diabetes · doi:10.2337/diabetes.49.9.1500 · Cited by 209 · cited 1×
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“This increases Ca2+ influx via the L-type Ca2+ channels (Figures 4C and 4D), in agreement with previous results in b cells (Shibasaki et al., 2004).”
ResultSelf-citationInterplay of Nutrients and Hormones in the Regulation of Glucagon Release*
PIPELEERS, D. G., SCHUIT, F. C., SCHRAVENDIJK, C. F. H. V., & WINKEL, M. V. D. (1985) · Endocrinology · doi:10.1210/endo-117-3-817 · Cited by 169 · 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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“The inhibitory effect of ω-conotoxin is as strong as that produced by the broadspectrum Ca-channel blocker Co (Gromada et al., 2004).”
BackgroundInfluentialSelf-citationOlsen, H. L., Theander, S., Bokvist, K., Buschard, K., Wollheim, C. B., & Gromada, J. (2005) · Endocrinology · doi:10.1210/en.2005-0800 · Cited by 156 · cited 1×
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BackgroundGlucagon Stimulates Exocytosis in Mouse and Rat Pancreatic α-Cells by Binding to Glucagon Receptors
Ma, X., Zhang, Y., Gromada, J., Sewing, S., Berggren, P., Buschard, K., Salehi, A. A., Vikman, J., Rorsman, P., & Eliasson, L. (2004) · Molecular Endocrinology · doi:10.1210/me.2004-0059 · Cited by 130 · cited 4×
“We have previously observed that GLP-1 when applied to a cells exposed to 5 mM glucose stimulates exocytosis (Ma et al., 2005).”
BackgroundMethodInfluentialSelf-citationLiu, Y.-J., Vieira, E., & Gylfe, E. (2004) · Cell Calcium · doi:10.1016/j.ceca.2003.10.002 · Cited by 118 · cited 2×
“It has been suggested that adrenaline depolarizes the a cell through a store-operated mechanism (Liu et al., 2004).”
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“GLP-1R immunoreactivity in mouse pancreases was detected using methods similar to those reported elsewhere (Braun et al., 2009) using rabbit anti-GLP1R (LS-A-1205 and LS-A-1206, Lifespan, 1:100 and 1:750, respectively) antibodies.”
MethodSelf-citationThe GluCre‐ROSA26EYFP mouse: A new model for easy identification of living pancreatic α‐cells
Quoix, N., Rui, C.-X., Guiot, Y., Herrera, P., Henquin, J., & Gilon, P. (2007) · FEBS Letters · doi:10.1016/j.febslet.2007.07.068 · Cited by 87 · cited 2×
“This suggests that the majority of cells active in 1 mM glucose are α-cells (Berts et al., 1996; Quoix et al., 2007).”
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“Addition of adrenaline in the combined presence of isradipine and u-conotoxin evoked a transient elevation of [Ca2+]i, possibly reflecting the a1-adrenoceptor-evoked response previously described in isolated mouse a cells (Vieira et al., 2004).”
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“For comparison, the plasma concentrations of adrenaline in mice range from a basal 1–30 nM during severe stress (Grouzmann et al., 2003).”
BackgroundAutonomic nervous control of the endocrine secretion from the isolated, perfused pig pancreas
Holst, J. J., Schwartz, T. W., Knuhtsen, S., Jensen, S. L., & Nielsen, O. V. (1986) · Journal of the Autonomic Nervous System · doi:10.1016/0165-1838(86)90045-7 · Cited by 61 · cited 2×
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“, 2008), endothelium (Bucci et al., 2004), liver, and kidney (Xu et al.”
BackgroundSuppression of Ca2+ oscillations in glucagon-producing α2-cells by insulin/glucose and amino acids
Berts, A., Ball, A., Gylfe, E., & Hellman, B. (1996) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/0167-4889(95)00173-5 · Cited by 50 · cited 2×
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“This low level of expression is in agreement with previous PCR and immunocytochemical data (Moens et al., 2002; Tornehave et al., 2008).”
ResultBidasee, K. R., Zheng, H., Shao, C. H., Parbhu, S. K., Rozanski, G. J., & Patel, K. P. (2008) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00103.2008 · Cited by 40 · cited 2×
“Diabetes has been reported to be associated with reduced expression of b-adrenergic receptors in the heart (Bidasee et al., 2008), endothelium (Bucci et al.”
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“The inhibi- tion produced by 1–10 nM forskolin is not due to stimulation of somatostatin secretion (Figure S2) or insulin secretion (data not shown, but see McQuaid et al., 2006).”
BackgroundChong-tao, X., Arinze, I., Johnson, J., Tuy, T. T., Bone, F., Ernsberger, P. R., & Massillon, D. (2007) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2007.05.001 · Cited by 10 · cited 1×
“Diabetes has been reported to be associated with reduced expression of b-adrenergic receptors in the heart (Bidasee et al., 2008), endothelium (Bucci et al., 2004), liver, and kidney (Xu et al., 2008).”
BackgroundSomatostatin-like immunoreactivity in man. Measurement in peripheral plasma.
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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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