SSTR2 is the functionally dominant somatostatin receptor in human pancreatic β- and α-cells
Open accessAbstract
Somatostatin-14 (SST) inhibits insulin and glucagon secretion by activating G protein-coupled somatostatin receptors (SSTRs), of which five isoforms exist (SSTR1–5). In mice, the effects on pancreatic β-cells are mediated by SSTR5, whereas α-cells express SSTR2. In both cell types, SSTR activation results in membrane hyperpolarization and suppression of exocytosis. Here, we examined the mechanisms by which SST inhibits secretion from human β- and α-cells and the SSTR isoforms mediating these effects. Quantitative PCR revealed high expression of SSTR2, with lower levels of SSTR1, SSTR3, and SSTR5, in human islets. Immunohistochemistry showed expression of SSTR2 in both β- and α-cells. SST application hyperpolarized human β-cells and inhibited action potential firing. The membrane hyperpolarization was unaffected by tolbutamide but antagonized by tertiapin-Q, a blocker of G protein-gated inwardly rectifying K+ channels (GIRK). The effect of SST was mimicked by an SSTR2-selective agonist, whereas a SSTR5 agonist was marginally effective. SST strongly (>70%) reduced depolarization-evoked exocytosis in both β- and α-cells. A slightly weaker inhibition was observed in both cell types after SSTR2 activation. SSTR3- and SSTR1-selective agonists moderately reduced the exocytotic responses in β- and α-cells, respectively, whereas SSTR4- and SSTR5-specific agonists were ineffective. SST also reduced voltage-gated P/Q-type Ca 2+ currents in β-cells, but normalization of Ca 2+ influx to control levels by prolonged depolarizations only partially restored exocytosis. We conclude that SST inhibits secretion from both human β- and α-cells by activating GIRK and suppressing electrical activity, reducing P/Q-type Ca 2+ currents, and directly inhibiting exocytosis. These effects are mediated predominantly by SSTR2 in both cell types.
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Adrenaline and somatostatin lead to transient repolarization and suppression of glucose-induced electrical activity in human β-cells.
“Adrenaline and somatostatin lead to transient repolarization and suppression of glucose-induced electrical activity (327, 568).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [327]
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- Authors
- Kailey, B., van de Bunt, M., Cheley, S., Johnson, P. R., MacDonald, P. E., Gloyn, A. L., Rorsman, P., & Braun, M.
- Affiliations
- University of Oxford (GB)
- Oxford Centre for Diabetes, Endocrinology, and Metabolism, University of Oxford, Oxford, United Kingdom;
- University of Alberta (CA)
- John Radcliffe Hospital (GB)
- National Institute for Health and Care Research (GB)
- Corresponding author
- Braun, Matthias
- ORCID
- Venue
- American Journal of Physiology-Endocrinology and Metabolism
- Publisher
- American Physiological Society
- Published
- 2012-11-01
- Volume
- 303
- Issue
- 9
- Pages
- E1107-E1116
- ISSN
- 0193-1849 (ISSN-L)
- 1522-1555
- PMC
- PMC3492856
- OpenAlex
- W2144387356
- Cited by
- 164
- References
- 6
- Citations by year
- 2026: 16 · 2025: 14 · 2024: 15 · 2023: 13 · 2022: 12 · 2021: 17 · 2020: 14 · 2019: 13 · 2018: 10 · 2017: 7 · 2016: 6 · 2015: 9 · 2014: 7 · 2013: 10 · 2012: 1
- FWCI
- 8.79
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- American Journal of Physiology-Endocrinology and Metabolism (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Wellcome Trust (095331/Z/11/Z, 095101, 095531/Z/11/Z, 095531, 95101/Z/10/Z)
- Canadian Institutes of Health Research (106435_1)
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- somatostatin, somatostatin receptor 2, somatostatin receptor 5, pancreatic beta cells, alpha cells, insulin secretion, glucagon secretion, membrane hyperpolarization, exocytosis, G protein-coupled receptors, G protein-coupled inwardly rectifying potassium channels, tertiapin-Q, action potential firing, human pancreatic islets
- MeSH terms
- Cells, Cultured, Exocytosis, Gene Expression Regulation, Humans, Immunohistochemistry, Islets of Langerhans, Kinetics, Membrane Potentials, Recombinant Proteins, RNA, Messenger, Somatostatin, Receptors, Somatostatin, Patch-Clamp Techniques, Calcium Signaling, Protein Isoforms, Protein Subunits, Potassium Channel Blockers, Glucagon-Secreting Cells, Insulin-Secreting Cells, G Protein-Coupled Inwardly-Rectifying Potassium Channels
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