title: Glucose principally regulates insulin secretion in mouse islets by controlling the numbers of granule fusion events per cell.
abstract: OBJECTIVE
  In dispersed single beta cells the response of each cell to glucose is heterogeneous. In contrast, within an islet, cell-to-cell communication leads to glucose inducing a more homogeneous response. For example, increases in NAD(P)H and calcium are relatively uniform across the cells of the islet. These data suggest that secretion of insulin from single beta cells within an islet should also be relatively homogeneous. The aim of this study was to test this hypothesis by determining the glucose dependence of single-cell insulin responses within an islet.
  
  
  METHODS
  Two-photon microscopy was used to detect the glucose-induced fusion of single insulin granules within beta cells in intact mouse islets.
  
  
  RESULTS
  First, we validated our assay and showed that the measures of insulin secretion from whole islets could be explained by the time course and numbers of granule fusion events observed. Subsequent analysis of the patterns of granule fusion showed that cell recruitment is a significant factor, accounting for a fourfold increase from 3 to 20 mmol/l glucose. However, the major factor is the regulation of the numbers of granule fusion events within each cell, which increase ninefold over the range of 3 to 20 mmol/l glucose. Further analysis showed that two types of granule fusion event occur: 'full fusion' and 'kiss and run'. We show that the relative frequency of each type of fusion is independent of glucose concentration and is therefore not a factor in the control of insulin secretion.
  
  
  CONCLUSIONS
  Within an islet, glucose exerts its main effect through increasing the numbers of insulin granule fusion events within a cell.
authors.affiliation: School of Biomedical Sciences, University of Queensland, St Lucia, QLD, 4072, Australia.
authors.forename: Jiun T
authors.initials: JT
authors.lastname: Low
authors.forename: Justin M
authors.initials: JM
authors.lastname: Mitchell
authors.forename: Oanh H
authors.initials: OH
authors.lastname: Do
authors.forename: Jacinda
authors.initials: J
authors.lastname: Bax
authors.forename: Alicia
authors.initials: A
authors.lastname: Rawlings
authors.forename: Michael
authors.initials: M
authors.lastname: Zavortink
authors.forename: Garry
authors.initials: G
authors.lastname: Morgan
authors.forename: Robert G
authors.initials: RG
authors.lastname: Parton
authors.forename: Herbert Y
authors.initials: HY
authors.lastname: Gaisano
authors.forename: Peter
authors.initials: P
authors.lastname: Thorn
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism*; D005089:Exocytosis / Q000502:physiology; D005947:Glucose / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism*; D008561:Membrane Fusion / Q000502:physiology; D051379:Mice; D008815:Mice, Inbred Strains; D008856:Microscopy, Fluorescence; D008954:Models, Biological
chemical_list: D001786:Blood Glucose; D007328:Insulin; D005947:Glucose