title: Insulin secretion from human beta cells is heterogeneous and dependent on cell-to-cell contacts.
abstract: OBJECTIVE
  We assessed the heterogeneity of insulin secretion from human isolated beta cells and its regulation by cell-to-cell contacts.
  
  
  METHODS
  Insulin secretion from single and paired cells was assessed by a reverse haemolytic plaque assay. The percentage of plaque-forming cells, the mean plaque area and the total plaque development were evaluated after 1 h of stimulation with different secretagogues.
  
  
  RESULTS
  Not all beta cells were surrounded by a haemolytic plaque under all conditions tested. A small fraction of the beta cell population (20%) secreted more than 90% and 70% of total insulin at 2.2 and 22.2 mmol/l glucose, respectively. Plaque-forming cells, mean plaque area and total plaque development were increased at 12.2 and 22.2 compared with 2.2 mmol/l glucose. Insulin secretion of single beta cells was similar at 12.2 and 22.2 mmol/l glucose. Insulin secretion of beta cell pairs was increased compared with that of single beta cells and was higher at 22.2 than at 12.2 mmol/l glucose. Insulin secretion of beta cells in contact with alpha cells was also increased compared with single beta cells, but was similar at 22.2 compared with 12.2 mmol/l glucose. Delta and other non-beta cells did not increase insulin secretion of contacting beta cells compared with that of single beta cells. Differences in insulin secretion between 22.2 and 12.2 mmol/l glucose were observed in murine but not in human islets.
  
  
  CONCLUSIONS
  Human beta cells are highly heterogeneous in terms of insulin secretion so that a small fraction of beta cells contributes to the majority of insulin secreted. Homologous and heterologous intercellular contacts have a significant impact on insulin secretion and this could be related to the particular architecture of human islets.
authors.affiliation: Cell Isolation and Transplantation Center, Department of Surgery, Geneva University Hospitals, 1 rue Michel Servet, Genève-4, Switzerland.
authors.forename: A
authors.initials: A
authors.lastname: Wojtusciszyn
authors.forename: M
authors.initials: M
authors.lastname: Armanet
authors.forename: P
authors.initials: P
authors.lastname: Morel
authors.forename: T
authors.initials: T
authors.lastname: Berney
authors.forename: D
authors.initials: D
authors.lastname: Bosco
mesh_terms: D000818:Animals; D002450:Cell Communication / Q000502:physiology*; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000378:metabolism*; D007515:Islets of Langerhans / Q000166:cytology / Q000378:metabolism*; D008297:Male; D051379:Mice
chemical_list: D007328:Insulin; D005947:Glucose