Somatostatin secreted by islet δ-cells fulfills multipleRoles as a paracrine regulator of islet function

Abstract

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.