Neurotransmitter-Induced Inhibition of Exocytosis in Insulin-Secreting β Cells by Activation of Calcineurin
Open accessAbstract
Neurotransmitters and hormones such as somatostatin, galanin, and adrenalin reduce insulin secretion. Their inhibitory action involves direct interference with the exocytotic machinery. We have examined the molecular processes underlying this effect using high resolution measurements of cell capacitance. Suppression of exocytosis was maximal at concentrations that did not cause complete inhibition of glucose-stimulated electrical activity. This action was dependent on activation of G proteins but was not associated with inhibition of the voltage-dependent Ca2+ currents or adenylate cyclase activity. The molecular processes initiated by the agonists culminate in the activation of the Ca(2+)-dependent protein phosphatase calcineurin, and suppression of the activity of this enzyme abolishes their action on exocytosis. We propose that mechanisms similar to those we report here may contribute to adrenergic and peptidergic inhibition of secretion in other neuroendocrine cells and in nerve terminals.
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Somatostatin and adrenaline transiently repolarise the β-cell and inhibit action potential firing and insulin secretion.
“A number of hormones and neurotransmitters (e.g. somatostatin and adrenaline) transiently repolarise the β-cell and inhibit action potential firing and insulin secretion (154, 543).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [543]
The Discussion (page unavailable) says adrenalin transiently repolarizes β-cells and lengthens electrically silent intervals; the Abstract says both adrenalin and somatostatin reduce insulin secretion. The Results (page unavailable) show that somatostatin reversibly lengthened silent intervals in some cells, but did not completely inhibit electrical activity and had no electrical effect in two of five cells. The paper therefore does not establish transient repolarization and inhibition of action-potential firing as uniform effects of somatostatin. (LLM, conf=0.85)
Experimental — accuracy not yet measuredInhibitory agonists like somatostatin and adrenaline act on late steps of exocytosis to reduce insulin release, for example by depriming of granules.
“Inhibitory agonists (like somatostatin and adrenaline) also act on late steps of exocytosis to reduce insulin release, for example by depriming of granules (240, 543).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [543]
The Abstract and Discussion report that somatostatin and adrenalin inhibit insulin secretion by acting directly on exocytosis at a step distal to the rise in cytoplasmic Ca2+. They identify calcineurin activation as the mechanism, but do not establish depriming of granules as an example of that action. (LLM, conf=0.87)
Experimental — accuracy not yet measuredThere is evidence that somatostatin's inhibitory effect on exocytosis is mediated by activation of the protein phosphatase calcineurin.
“There is some evidence that somatostatin’s inhibitory effect on exocytosis is mediated by activation of the protein phosphatase calcineurin (543), possibly by dephosphorylation of the same serine residue in Syt7 that is phosphorylated in the presence of GLP-1 (735).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [543]
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Research works printed but not linked: 9
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- Authors
- Renström, E., Ding, W.-G., Bokvist, K., & Rorsman, P.
- Affiliations
- Novo Nordisk (Denmark) (DK)
- Corresponding author
- Rorsman, Patrik
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 1996-09
- Volume
- 17
- Issue
- 3
- Pages
- 513-522
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W2013739856
- Cited by
- 186
- References
- 0
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 1 · 2023: 2 · 2022: 2 · 2021: 2 · 2020: 3 · 2019: 6 · 2018: 10 · 2017: 4 · 2016: 2 · 2015: 4 · 2014: 9 · 2013: 6 · 2012: 5
- FWCI
- 9.99
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
- Keywords
- insulin secretion, exocytosis, pancreatic beta cells, calcineurin, neurotransmitter inhibition, somatostatin, galanin, adrenergic inhibition, G protein signaling, cell membrane capacitance, neuroendocrine cells
- MeSH terms
- Insulin Secretion, Adrenergic Agonists, Animals, Calcium, Calmodulin-Binding Proteins, Cells, Cultured, Clonidine, Cytoplasm, Electrophysiology, Enzyme Activation, Epinephrine, Exocytosis, Guanine, Hormone Antagonists, Insecticides, Insulin, Islets of Langerhans, Mice, Inbred Strains, Nitriles, Phosphoprotein Phosphatases, Pyrethrins, Somatostatin, Neurotransmitter Agents, Galanin, GTP-Binding Proteins, Calcineurin, Mice
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