title: A role for islet somatostatin in mediating sympathetic regulation of glucagon secretion.
abstract: OBJECTIVE
  Somatostatin (SST) released from islet δ-cells inhibits both insulin and glucagon secretion but the role of this tonic inhibition is unclear. In this study we investigated whether δ-cell SST may facilitate sympathetic regulation of glucagon secretion as part of an 'accelerator/brake' mechanism.
  
  
  METHODS
  The secretory characteristics of islets isolated from SST-deficient (Sst-/-) and control mouse islets were assessed in static incubation studies. Glucagon and SST release was measured by radioimmunoassay (RIA).
  
  
  RESULTS
  Arginine stimulated both glucagon and SST release from control mouse islets whereas the sympathetic neurotransmitter noradrenaline (NA) increased glucagon secretion but inhibited SST release in the presence of 2 mmol/l glucose or 20 mmol/l arginine. Experiments were performed using Sst-/- islets to assess whether the reduction of SST secretion by NA offers an indirect mechanism of enhancing glucagon release in response to sympathetic activation. Arginine-induced but not NA-induced glucagon release from Sst-/- islets was significantly increased compared to controls. In combination, NA enhanced arginine-induced release from both groups of mouse islets but to a greater extent in control islets, leading to similar overall levels of glucagon release. The responsiveness of Sst-/- islets to NA was thus blunted under stimulatory but not sub-stimulatory conditions of SST release.
  
  
  CONCLUSIONS
  Our data suggest that sympathetic activation of glucagon release may be partly mediated by an indirect effect on SST secretion, where the tonic inhibition by δ-cell SST on α-cells is removed, facilitating precise and substantial changes in glucagon release in response to NA.
authors.affiliation: Diabetes Research Group, 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: Keith
authors.initials: K
authors.lastname: Fairhall
authors.forename: Shanta J
authors.initials: SJ
authors.lastname: Persaud
authors.forename: Peter M
authors.initials: PM
authors.lastname: Jones
mesh_terms: D000818:Animals; D001120:Arginine / Q000378:metabolism; D005260:Female; D005934:Glucagon / Q000378:metabolism*; D050416:Glucagon-Secreting Cells / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000378:metabolism; D007515:Islets of Langerhans / Q000294:innervation* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D009638:Norepinephrine / Q000378:metabolism; D009924:Organ Culture Techniques; D019899:Paracrine Communication; D013004:Somatostatin / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D013564:Sympathetic Nervous System / Q000378:metabolism*; D009435:Synaptic Transmission
chemical_list: D013004:Somatostatin; D005934:Glucagon; D001120:Arginine; D005947:Glucose; D009638:Norepinephrine