R-type Ca2+-channel-evoked CICR regulates glucose-induced somatostatin secretion
Abstract
Pancreatic islets have a central role in blood glucose homeostasis. In addition to insulin-producing beta-cells and glucagon-secreting alpha-cells, the islets contain somatostatin-releasing delta-cells. Somatostatin is a powerful inhibitor of insulin and glucagon secretion. It is normally secreted in response to glucose and there is evidence suggesting its release becomes perturbed in diabetes. Little is known about the control of somatostatin release. Closure of ATP-regulated K(+)-channels (K(ATP)-channels) and a depolarization-evoked increase in cytoplasmic free Ca(2+) concentration ([Ca(2+)](i)) have been proposed to be essential. Here, we report that somatostatin release evoked by high glucose (>or=10 mM) is unaffected by the K(ATP)-channel activator diazoxide and proceeds normally in K(ATP)-channel-deficient islets. Glucose-induced somatostatin secretion is instead primarily dependent on Ca(2+)-induced Ca(2+)-release (CICR). This constitutes a novel mechanism for K(ATP)-channel-independent metabolic control of pancreatic hormone secretion.
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Ryr3 is highly expressed in somatostatin-secreting δ-cells.
“In contrast, Ryr3 is highly expressed in somatostatin-secreting δ-cells (760).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [760]
The reported effects of ryanodine in mouse islets may actually be a consequence of the paracrine action of somatostatin.
“Therefore, the reported effects of ryanodine in mouse islets may actually be a consequence of the paracrine action of somatostatin.”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [760]
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Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men
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Self-citationReversible changes in pancreatic islet structure and function produced by elevated blood glucose
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Self-citationGlucose controls glucagon secretion by directly modulating cAMP in alpha cells
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CFTR is involved in the regulation of glucagon secretion in human and rodent alpha cells
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- Authors
- Zhang, Q., Bengtsson, M., Partridge, C., Salehi, A., Braun, M., Cox, R., Eliasson, L., Johnson, P. R., Renström, E., Schneider, T., Berggren, P.-O., Göpel, S., Ashcroft, F. M., & Rorsman, P.
- Affiliations
- Lund University (SE)
- Churchill Hospital (GB)
- Medical Research Council (GB)
- John Radcliffe Hospital (GB)
- University of Cologne (DE)
- Karolinska Institutet (SE)
- AstraZeneca (Sweden) (SE)
- University of Oxford (GB)
- Corresponding author
- Rorsman, Patrik
- ORCID
- Venue
- Nature Cell Biology
- Published
- 2007-03-18
- Volume
- 9
- Issue
- 4
- Pages
- 453-460
- ISSN
- 1465-7392 (ISSN-L)
- 1476-4679
- OpenAlex
- W2050461207
- Cited by
- 110
- References
- 2
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 3 · 2023: 3 · 2022: 3 · 2021: 11 · 2020: 7 · 2019: 11 · 2018: 6 · 2017: 7 · 2016: 3 · 2015: 5 · 2014: 9 · 2013: 5 · 2012: 6
- FWCI
- 6.65
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Funders
- Wellcome Trust
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
- Keywords
- somatostatin secretion, calcium-induced calcium release, R-type calcium channels, pancreatic delta cells, glucose-stimulated secretion, ATP-sensitive potassium channels, diazoxide, pancreatic islets, blood glucose homeostasis, diabetes mellitus
- MeSH terms
- Animals, Calcium, Cytophotometry, Diazoxide, Dose-Response Relationship, Drug, Electrophysiology, Glucose, Immunohistochemistry, Islets of Langerhans, Mannoheptulose, Membrane Potentials, Mice, Inbred C57BL, Mice, Inbred Strains, Oxazoles, Potassium, Ryanodine, Somatostatin, Potassium Channels, Isradipine, Mice, Knockout, Microscopy, Confocal, Somatostatin-Secreting Cells, Calcium Channels, R-Type, Potassium Channel Blockers, Macrocyclic Compounds, Mice, In Vitro Techniques
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