title: The role of the transcription factor ETV5 in insulin exocytosis.
abstract: OBJECTIVE
  Genome-wide association studies have revealed an association of the transcription factor ETS variant gene 5 (ETV5) with human obesity. However, its role in glucose homeostasis and energy balance is unknown.
  
  
  METHODS
  Etv5 knockout (KO) mice were monitored weekly for body weight (BW) and food intake. Body composition was measured at 8 and 16 weeks of age. Glucose metabolism was studied, and glucose-stimulated insulin secretion was measured in vivo and in vitro.
  
  
  RESULTS
  Etv5 KO mice are smaller and leaner, and have a reduced BW and lower fat mass than their wild-type controls on a chow diet. When exposed to a high-fat diet, KO mice are resistant to diet-induced BW gain. Despite a greater insulin sensitivity, KO mice have profoundly impaired glucose tolerance associated with impaired insulin secretion. Morphometric analysis revealed smaller islets and a reduced beta cell size in the pancreatic islets of Etv5 KO mice. Knockdown of ETV5 in an insulin-secreting cell line or beta cells from human donors revealed intact mitochondrial and Ca(2+) channel activity, but reduced insulin exocytosis.
  
  
  CONCLUSIONS
  This work reveals a critical role for ETV5 in specifically regulating insulin secretion both in vitro and in vivo.
authors.affiliation: Department of Internal Medicine, University of Cincinnati, 2170 East Galbraith Road, Cincinnati, OH, 45237, USA.
authors.forename: Ruth
authors.initials: R
authors.lastname: Gutierrez-Aguilar
authors.forename: Dong-Hoon
authors.initials: DH
authors.lastname: Kim
authors.forename: Marina
authors.initials: M
authors.lastname: Casimir
authors.forename: Xiao-Qing
authors.initials: XQ
authors.lastname: Dai
authors.forename: Paul T
authors.initials: PT
authors.lastname: Pfluger
authors.forename: Jongsun
authors.initials: J
authors.lastname: Park
authors.forename: April
authors.initials: A
authors.lastname: Haller
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Donelan
authors.forename: Jisoo
authors.initials: J
authors.lastname: Park
authors.forename: David
authors.initials: D
authors.lastname: D'Alessio
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Woods
authors.forename: Patrick E
authors.initials: PE
authors.lastname: MacDonald
authors.forename: Randy J
authors.initials: RJ
authors.lastname: Seeley
mesh_terms: D000818:Animals; D001823:Body Composition; D001835:Body Weight; D002096:C-Peptide / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D059305:Diet, High-Fat; D004435:Eating; D005089:Exocytosis / Q000502:physiology*; D055106:Genome-Wide Association Study; D005947:Glucose / Q000378:metabolism*; D005951:Glucose Tolerance Test; D006706:Homeostasis / Q000502:physiology*; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D000078790:Insulin Secretion; D051379:Mice; D018345:Mice, Knockout; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D002096:C-Peptide; D004268:DNA-Binding Proteins; C513242:Etv5 protein, mouse; D007328:Insulin; D014157:Transcription Factors; D005947:Glucose