title: Delta cell secretory responses to insulin secretagogues are not mediated indirectly by insulin.
abstract: OBJECTIVE
  Somatostatin from islet delta cells inhibits insulin and glucagon secretion, but knowledge of the regulation of pancreatic somatostatin release is limited. Some insulin secretagogues stimulate somatostatin secretion, and here we investigated whether delta cell secretory responses are indirectly regulated in a paracrine manner by insulin released from beta cells.
  
  
  METHODS
  Hormone release from static incubations of primary mouse islets or somatostatin-secreting TGP52 cells was measured by RIA. mRNA expression was assessed by RT-PCR.
  
  
  RESULTS
  Glucose and a range of other physiological and pharmacological agents stimulated insulin and somatostatin release, and insulin receptor mRNA was expressed in islets, MIN6 beta cells and TGP52 cells. However, exogenous insulin did not modulate basal or glucose-induced somatostatin secretion from islets, nor did pre-incubation with an antibody against the insulin receptor or with the insulin receptor tyrosine kinase inhibitor, HNMPA(AM)(3). Glucose and tolbutamide stimulated somatostatin release from TGP52 cells, whereas a range of receptor-operating agents had no effect, the latter being consistent with a lack of corresponding receptor mRNA expression in these cells. Parasympathetic activation stimulated insulin, but inhibited somatostatin release from mouse islets in accordance with differences in muscarinic receptor mRNA expression in islets, MIN6 and TGP52 cells. The inhibitory effect on somatostatin secretion was reversed by pertussis toxin or the muscarinic receptor 2 antagonist, methoctramine.
  
  
  CONCLUSIONS
  A number of insulin secretagogues have analogous effects on insulin and somatostatin release, but this similarity of response is not mediated by an indirect, paracrine action of insulin on delta cells.
authors.affiliation: Diabetes Research Group, Division of Diabetes and Nutritional Sciences, School of Medicine, King's College London, Guy's Campus, London Bridge, London SE1 1UL, UK. astrid.hauge_evans@kcl.ac.uk
authors.forename: A C
authors.initials: AC
authors.lastname: Hauge-Evans
authors.forename: R L
authors.initials: RL
authors.lastname: Anderson
authors.forename: S J
authors.initials: SJ
authors.lastname: Persaud
authors.forename: P M
authors.initials: PM
authors.lastname: Jones
mesh_terms: D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D007328:Insulin / Q000378:metabolism* / Q000494:pharmacology; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D011972:Receptor, Insulin / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019864:Somatostatin-Secreting Cells / Q000378:metabolism*
chemical_list: D007328:Insulin; D011972:Receptor, Insulin