title: Somatostatin secreted by islet delta-cells fulfills multiple roles as a paracrine regulator of islet function.
abstract: OBJECTIVE
  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.
  
  
  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 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Beta Cell Development and Function Group, Division of Reproduction and Endocrinology, King's College London, London, UK. astrid.hauge_evans@kcl.ac.uk
authors.forename: Astrid C
authors.initials: AC
authors.lastname: Hauge-Evans
authors.forename: Aileen J
authors.initials: AJ
authors.lastname: King
authors.forename: Danielle
authors.initials: D
authors.lastname: Carmignac
authors.forename: Carolyn C
authors.initials: CC
authors.lastname: Richardson
authors.forename: Iain C A F
authors.initials: IC
authors.lastname: Robinson
authors.forename: Malcolm J
authors.initials: MJ
authors.lastname: Low
authors.forename: Michael R
authors.initials: MR
authors.lastname: Christie
authors.forename: Shanta J
authors.initials: SJ
authors.lastname: Persaud
authors.forename: Peter M
authors.initials: PM
authors.lastname: Jones
mesh_terms: D000818:Animals; D005260:Female; D005934:Glucagon / Q000378:metabolism; D007150:Immunohistochemistry; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D016133:Polymerase Chain Reaction; D011863:Radioimmunoassay; D013004:Somatostatin / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D019864:Somatostatin-Secreting Cells / Q000378:metabolism*
chemical_list: D007328:Insulin; D013004:Somatostatin; D005934:Glucagon