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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 Sst^sup -/-^ 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^sup -/-^ mice in vivo and from isolated islets in vitro.
RESULTS-Islet size and organization did not differ between Sst^sup -/-^ and control islets, nor did islet glucagon or insulin content. Sst^sup -/-^ mice showed enhanced insulin and glucagon secretory responses in vivo. In vitro stimulus-induced insulin and glucagon secretion was enhanced from perifused Sst^sup -/-^ islets compared with control islets and was inhibited by exogenous SST in Sst^sup -/-^ 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^sup -/-^ islets compared with controls. Glucose suppressed glucagon secretion from control but not Sst^sup -/-^ 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. Diabetes 58:403-411, 2009
Islets of Langerhans are heterogeneous cell aggregates containing β-, α-, δ-, and PP cells, which secrete insulin, glucagon, somatostatin (SST), and pancreatic polypeptide, respectively. The different cell types within the islet are affected by changes in the extracellular glucose concentration. Thus, elevations in circulating glucose stimulate insulin secretion from islet β-cells and inhibit glucagon secretion from a-cells as part of the reciprocal regulation of blood glucose by insulin and glucagon. SST secretion from islet δ-cells is also stimulated by increased extracellular glucose, although the threshold concentration for d-cells to respond to glucose is lower than that for β-cells (1), and the ionic events in stimulus-response coupling differ between β- and δ-cells (2).
Rodent islets have a defined architecture with...