Abstract

Objective: Somatostatin (SST) is secreted by islet δ-cells and by extra-islet 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 intra-islet function of δ-cell SST remains uncertain. We have used Sst^−/− 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 organisation 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 to 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 to 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 suppression of glucagon secretion.