title: Mice deficient in GEM GTPase show abnormal glucose homeostasis due to defects in beta-cell calcium handling.
abstract: OBJECTIVE
  Glucose-stimulated insulin secretion from beta-cells is a tightly regulated process that requires calcium flux to trigger exocytosis of insulin-containing vesicles. Regulation of calcium handling in beta-cells remains incompletely understood. Gem, a member of the RGK (Rad/Gem/Kir) family regulates calcium channel handling in other cell types, and Gem over-expression inhibits insulin release in insulin-secreting Min6 cells. The aim of this study was to explore the role of Gem in insulin secretion. We hypothesised that Gem may regulate insulin secretion and thus affect glucose tolerance in vivo.
  
  
  METHODS
  Gem-deficient mice were generated and their metabolic phenotype characterised by in vivo testing of glucose tolerance, insulin tolerance and insulin secretion. Calcium flux was measured in isolated islets.
  
  
  RESULTS
  Gem-deficient mice were glucose intolerant and had impaired glucose stimulated insulin secretion. Furthermore, the islets of Gem-deficient mice exhibited decreased free calcium responses to glucose and the calcium oscillations seen upon glucose stimulation were smaller in amplitude and had a reduced frequency.
  
  
  CONCLUSIONS
  These results suggest that Gem plays an important role in normal beta-cell function by regulation of calcium signalling.
authors: Diabetes and Transcription Factors Group, Garvan Institute of Medical Research, Sydney, Australia. j.gunton@garvan.org.au
authors: Jenny E
authors: JE
authors: Gunton
authors: Mary
authors: M
authors: Sisavanh
authors: Rebecca A
authors: RA
authors: Stokes
authors: Jon
authors: J
authors: Satin
authors: Leslie S
authors: LS
authors: Satin
authors: Min
authors: M
authors: Zhang
authors: Sue M
authors: SM
authors: Liu
authors: Weikang
authors: W
authors: Cai
authors: Kim
authors: K
authors: Cheng
authors: Gregory J
authors: GJ
authors: Cooney
authors: D Ross
authors: DR
authors: Laybutt
authors: Trina
authors: T
authors: So
authors: Juan-Carlos
authors: JC
authors: Molero
authors: Shane T
authors: ST
authors: Grey
authors: Douglas A
authors: DA
authors: Andres
authors: Michael S
authors: MS
authors: Rolph
authors: Charles R
authors: CR
authors: Mackay
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000235:genetics; D005947:Glucose / Q000378:metabolism*; D018149:Glucose Intolerance / Q000235:genetics / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000235:genetics; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D020559:Monomeric GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D007328:Insulin; C088119:Gem protein, mouse; D020559:Monomeric GTP-Binding Proteins; D005947:Glucose; D002118:Calcium