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- Title
Somatostatin secreted by islet delta-cells fulfills multiple roles as a paracrine regulator of islet function.
- Authors
Hauge-Evans AC; King AJ; Carmignac D; Richardson CC; Robinson IC; Low MJ; Christie MR; Persaud SJ; Jones PM; Hauge-Evans, Astrid C; King, Aileen J; Carmignac, Danielle; Richardson, Carolyn C; Robinson, Iain C A F; Low, Malcolm J; Christie, Michael R; Persaud, Shanta J; Jones, Peter M
- Abstract
<bold>Objective: </bold>Somatostatin (SST) is secreted by islet delta-cells and by extraislet neuroendocrine cells. SST receptors have been identified on alpha- and beta-cells, and exogenous SST inhibits insulin and glucagon secretion, consistent with a role for SST in regulating alpha- and beta-cell function. However, the specific intraislet function of delta-cell SST remains uncertain. We have used Sst(-/-) mice to investigate the role of delta-cell SST in the regulation of insulin and glucagon secretion in vitro and in vivo.<bold>Research Design and Methods: </bold>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.<bold>Results: </bold>Islet size and organization did not differ between Sst(-/-) 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 Sst(-/-) but not control islets. No difference in the switch-off rate of glucose-stimulated insulin secretion was observed between genotypes, but the cholinergic agonist carbamylcholine enhanced glucose-induced insulin secretion to a lesser extent in Sst(-/-) islets compared with controls. Glucose suppressed glucagon secretion from control but not Sst(-/-) islets.<bold>Conclusions: </bold>We suggest that delta-cell SST exerts a tonic inhibitory influence on insulin and glucagon secretion, which may facilitate the islet response to cholinergic activation. In addition, delta-cell SST is implicated in the nutrient-induced suppression of glucagon secretion.
- Publication
Diabetes, 2009, Vol 58, Issue 2, p403
- ISSN
0012-1797
- Publication type
journal article
- DOI
10.2337/db08-0792