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  • Review Article
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The somatostatin-secreting pancreatic δ-cell in health and disease

Nature Reviews Endocrinology volume 14, pages 404–414 (2018)Cite this article

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Abstract

The somatostatin-secreting δ-cells comprise ~5% of the cells of the pancreatic islets. The δ-cells have complex morphology and might interact with many more islet cells than suggested by their low numbers. δ-Cells contain ATP-sensitive potassium channels, which open at low levels of glucose but close when glucose is elevated. This closure initiates membrane depolarization and electrical activity and increased somatostatin secretion. Factors released by neighbouring α-cells or β-cells amplify the glucose-induced effects on somatostatin secretion from δ-cells, which act locally within the islets as paracrine or autocrine inhibitors of insulin, glucagon and somatostatin secretion. The effects of somatostatin are mediated by activation of somatostatin receptors coupled to the inhibitory G protein, which culminates in suppression of the electrical activity and exocytosis in α-cells and β-cells. Somatostatin secretion is perturbed in animal models of diabetes mellitus, which might explain the loss of appropriate hypoglycaemia-induced glucagon secretion, a defect that could be mitigated by somatostatin receptor 2 antagonists. Somatostatin antagonists or agents that suppress somatostatin secretion have been proposed as an adjunct to insulin therapy. In this Review, we summarize the cell physiology of somatostatin secretion, what might go wrong in diabetes mellitus and the therapeutic potential of agents targeting somatostatin secretion or action.

Key points

  • The δ-cells of the pancreatic islets secrete somatostatin, a powerful paracrine inhibitor of both insulin and glucagon secretion from islet α-cells and β-cells.

  • δ-Cells are electrically excitable, and glucose stimulates action potential firing and somatostatin secretion by both metabolic and non-metabolic effects.

  • Factors (such as GABA and urocortin 3) released by the β-cells stimulate somatostatin secretion, thereby providing a mechanism for feedback control of insulin and glucagon secretion during hyperglycaemia.

  • Diabetes mellitus is associated with impaired glucagon secretion in response to hypoglycaemia; this effect is corrected by somatostatin antagonists, suggesting that diabetes mellitus involves hypersecretion of somatostatin during hypoglycaemia.

  • Agents that inhibit somatostatin secretion or action might reduce the risk of insulin-induced hypoglycaemia and should be considered as an adjunct to insulin therapy.

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Fig. 1: δ-Cell histology and somatostatin secretion.
Fig. 2: Regulation of somatostatin secretion by δ-cell electrical activity.
Fig. 3: Somatostatin signalling in pancreatic islets.

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Acknowledgements

Work discussed in this Review was supported by a Wellcome Trust Senior Investigator Award (095531), the Knut and Alice Wallenberg Foundation, the Swedish Research Council, the Hartwell Foundation for Biomedical Research (201500731), the Juvenile Diabetes Research Foundation (CDA-2-2013-54) and the US NIH (DK110276).

Reviewer information

Nature Reviews Endocrinology thanks P. Flatt and G. Weir for their contribution to the peer review of this work.

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Authors and Affiliations

  1. Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, Churchill Hospital, University of Oxford, Oxford, UK

    Patrik Rorsman

  2. Department of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden

    Patrik Rorsman

  3. Department of Neurobiology, Physiology and Behavior, College of Biological Sciences, University of California, Davis, Davis, CA, USA

    Mark O. Huising

  4. Department of Physiology and Membrane Biology, School of Medicine, University of California, Davis, Davis, CA, USA

    Mark O. Huising

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  1. Patrik Rorsman
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  2. Mark O. Huising
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P.R. and M.O.H. both researched the data for the article, provided substantial contributions to discussion of the content, wrote the article and reviewed and/or edited the manuscript before submission.

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Correspondence to Patrik Rorsman.

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Rorsman, P., Huising, M.O. The somatostatin-secreting pancreatic δ-cell in health and disease. Nat Rev Endocrinol 14, 404–414 (2018). https://doi.org/10.1038/s41574-018-0020-6

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