Somatostatin secreted by islet δ-Cells fulfills multiple roles as a paracrine regulator of islet function

Hauge-Evans, A. C., King, A. J., Carmignac, D. , Richardson, C. C., Robinson, I. C. A. F., Low, M. J., Christie, M. R., Persaud, S. J. and Jones, P. M. (2009) Somatostatin secreted by islet δ-Cells fulfills multiple roles as a paracrine regulator of islet function. Diabetes, 58 (2). pp. 403-411. ISSN 0012 1797

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OBJECTIVE-Somatostatin (SST) is secreted by islet δ-cells and by extraislet neuroendocrine cells. SST receptors have been identified on α- and β-cells, and exogenous SST inhibits insulin and glucagon secretion, consistent with a role for SST in regulating α- and β-cell function. However, the specific intraislet function of δ-cell SST remains uncertain. We have used S st-/- mice to investigate the role of δ-cell SST in the regulation of insulin and glucagon secretion in vitro and in vivo. RESEARCH DESIGN AND METHODS-Islet morphology was assessed by histological analysis. Hormone levels were measured by radioimmunoassay in control and Sst-/-mice in vivo and from isolated islets in vitro. RESULTS-Islet size and organization did not differ between S st-/- and control islets, nor did islet glucagon or insulin content. Sst-/- mice showed enhanced insulin and glucagon secretory responses in vivo. In vitro stimulus-induced insulin and glucagon secretion was enhanced from perifused Sst-/- islets compared with control islets and was inhibited by exogenous SST in S st-/- but not control islets. No difference in the switch-off rate of glucose-stimulated insulin secretion was observed between genotypes, but the cholinergic agonist carba-mylcholine enhanced glucose-induced insulin secretion to a lesser extent in S st-/- islets compared with controls. Glucose suppressed glucagon secretion from control but not Sst-/- islets. CONCLUSIONS-We suggest that δ-cell SST exerts a tonic inhibitory influence on insulin and glucagon secretion, which may facilitate the islet response to cholinergic activation. In addition, δ-cell SST is implicated in the nutrient-induced suppresion of glucagon secretion. Diabetes 58:403-411, 2009. © 2009 by the American Diabetes Association.

Keywords:carbachol, glucagon, insulin, somatostatin, somatostatin, animal experiment, animal tissue, article, controlled study, female, glucagon release, histology, hormonal regulation, immunohistochemistry, insulin release, mouse, nonhuman, pancreas islet delta cell, paracrine signaling, parasympathetic innervation, priority journal, somatostatin release, animal, cytology, genetics, male, metabolism, mouse mutant, pancreas islet, physiology, polymerase chain reaction, radioimmunoassay, secretion, somatostatin cell, Animals, Islets of Langerhans, Mice, Mice, Knockout, Somatostatin-Secreting Cells
Subjects:B Subjects allied to Medicine > B120 Physiology
Divisions:College of Science > School of Life Sciences
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ID Code:18115
Deposited On:31 Jul 2015 09:29

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