OBJECTIVE-Somatostatin (SST) is secreted by islet ␦-cells and by extraislet neuroendocrine cells. SST receptors have been identified on ␣-and -cells, and exogenous SST inhibits insulin and glucagon secretion, consistent with a role for SST in regulating ␣-and -cell function. However, the specific intraislet function of ␦-cell SST remains uncertain. We have used Sst Ϫ/Ϫ mice to investigate the role of ␦-cell SST in the regulation of insulin and glucagon secretion in vitro and in vivo.
RESEARCH DESIGN AND METHODS-Islet morphology wasassessed by histological analysis. Hormone levels were measured by radioimmunoassay in control and Sst Ϫ/Ϫ mice in vivo and from isolated islets in vitro.
RESULTS-Islet size and organization did not differ between
SstϪ/Ϫ and control islets, nor did islet glucagon or insulin content. Sst Ϫ/Ϫ mice showed enhanced insulin and glucagon secretory responses in vivo. In vitro stimulus-induced insulin and glucagon secretion was enhanced from perifused Sst Ϫ/Ϫ islets compared with control islets and was inhibited by exogenous SST in Sst Ϫ/Ϫ 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 Ϫ/Ϫ islets compared with controls. Glucose suppressed glucagon secretion from control but not Sst Ϫ/Ϫ islets.CONCLUSIONS-We suggest that ␦-cell SST exerts a tonic inhibitory influence on insulin and glucagon secretion, which may facilitate the islet response to cholinergic activation. In addition, ␦-cell SST is implicated in the nutrient-induced suppression of glucagon secretion. Diabetes 58:403-411, 2009