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Cited by 120Pancreatic function and diabetesCellular transport and secretionCalcium signaling and nucleotide metabolism

Somatostatin inhibits exocytosis in rat pancreatic α‐cells by G i2 ‐dependent activation of calcineurin and depriming of secretory granules

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Gromada, Jesper, Høy, Marianne, Buschard, Karsten, Salehi, Albert, Rorsman, Patrik·2001·The Journal of Physiology
DOI 10.1111/j.1469-7793.2001.00519.xPMC PMC2278803
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Abstract

1. Measurements of cell capacitance were used to investigate the molecular mechanisms by which somatostatin inhibits Ca(2+)-induced exocytosis in single rat glucagon-secreting pancreatic alpha-cells. 2. Somatostatin decreased the exocytotic responses elicited by voltage-clamp depolarisations by 80 % in the presence of cyclic AMP-elevating agents such as isoprenaline and forskolin. Inhibition was time dependent and half-maximal within 22 s. 3. The inhibitory action of somatostatin was concentration dependent with an IC(50) of 68 nM and prevented by pretreatment of the cells with pertussis toxin. The latter effect was mimicked by intracellular dialysis with specific antibodies to G(i1/2) and by antisense oligonucleotides against G proteins of the subtype G(i2). 4. Somatostatin lacked inhibitory action when applied in the absence of forskolin or in the presence of the L-type Ca(2+) channel blocker nifedipine. The size of the omega-conotoxin-sensitive and forskolin-independent component of exocytosis was limited to 60 fF. By contrast, somatostatin abolished L-type Ca(2+) channel-dependent exocytosis in alpha-cells exposed to forskolin. The magnitude of the latter pool amounted to 230 fF. 5. The inhibitory effect of somatostatin on exocytosis was mediated by activation of the serine/threonine protein phosphatase calcineurin and was prevented by pretreatment with cyclosporin A and deltamethrin or intracellularly applied calcineurin autoinhibitory peptide. Experiments using the stable ATP analogue AMP-PCP indicate that somatostatin acts by depriming of granules. 6. We propose that somatostatin receptors associate with L-type Ca(2+) channels and couple to G(i2) proteins leading to a localised activation of calcineurin and depriming of secretory granules situated close to the L-type Ca(2+) channels.

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  • Inhibitory 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 [240]

    The Discussion (page unavailable) reports that somatostatin inhibits exocytosis by depriming granules, but the experiments concern glucagon-releasing rat α-cells, not insulin-releasing cells. The Abstract (page unavailable) says adrenaline stimulates glucagon release; this paper does not establish adrenaline-induced depriming or reduced insulin release. (LLM, conf=0.89)

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Sorted by citations

Authors
Gromada, J., Høy, M., Buschard, K., Salehi, A., & Rorsman, P.
Affiliations
  • Novo Nordisk (Denmark) (DK)
  • Copenhagen Municipal Hospital (DK)
  • Lund University (SE)
Corresponding author
Rorsman, Patrik
ORCID
Venue
The Journal of Physiology
Publisher
Wiley
Published
2001-09
Volume
535
Issue
2
Pages
519-532
ISSN
  • 0022-3751 (ISSN-L)
  • 1469-7793
DOI
10.1111/j.1469-7793.2001.00519.x
PMC
PMC2278803
OpenAlex
W2050841721
Cited by
120
References
0
Citations by year
2026: 3 · 2025: 2 · 2024: 6 · 2023: 3 · 2022: 2 · 2021: 7 · 2020: 2 · 2019: 3 · 2018: 6 · 2017: 8 · 2016: 4 · 2015: 7 · 2014: 6 · 2013: 2 · 2012: 7
FWCI
6.66
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • The Journal of Physiology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Knut och Alice Wallenbergs Stiftelse
  • Vetenskapsrådet
  • Novo Nordisk Fonden
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
somatostatin, alpha cells, exocytosis, G protein-coupled receptors, calcineurin, L-type calcium channels, forskolin, glucagon secretion, pertussis toxin, cyclosporine, AMP-PCP, cell membrane capacitance
MeSH terms
Adenosine Triphosphate, Animals, Calcium, Calcium Channel Blockers, Cytoplasm, Exocytosis, Colforsin, Islets of Langerhans, Male, Membrane Potentials, Nifedipine, Phosphoric Monoester Hydrolases, Proto-Oncogene Proteins, Rats, Inbred Lew, Somatostatin, Patch-Clamp Techniques, GTP-Binding Protein alpha Subunits, Gi-Go, Calcineurin, Oligoribonucleotides, Antisense, Calcium Channels, L-Type, Calcium Channels, N-Type, omega-Conotoxin GVIA, Secretory Vesicles, Rats, GTP-Binding Protein alpha Subunit, Gi2

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