title: Short-term overexpression of VEGF-A in mouse beta cells indirectly stimulates their proliferation and protects against diabetes.
abstract: OBJECTIVE
  Vascular endothelial growth factor (VEGF) has been recognised by loss-of-function experiments as a pleiotropic factor with importance in embryonic pancreas development and postnatal beta cell function. Chronic, nonconditional overexpression of VEGF-A has a deleterious effect on beta cell development and function. We report, for the first time, a conditional gain-of-function study to evaluate the effect of transient VEGF-A overexpression by adult pancreatic beta cells on islet vasculature and beta cell proliferation and survival, under both normal physiological and injury conditions.
  
  
  METHODS
  In a transgenicmouse strain, overexpressing VEGF-A in a doxycycline-inducible and beta cell-specific manner, we evaluated the ability of VEGF-A to affect islet vessel density, beta cell proliferation and protection of the adult beta cell mass from toxin-induced injury.
  
  
  RESULTS
  Short-term VEGF-A overexpression resulted in islet hypervascularisation, increased beta cell proliferation and protection from toxin-mediated beta cell death, and thereby prevented the development of hyperglycaemia. Extended overexpression of VEGF-A led to impaired glucose tolerance, elevated fasting glycaemia and a decreased beta cell mass.
  
  
  CONCLUSIONS
  Overexpression of VEGF-A in beta cells time-dependently affects glycometabolic control and beta cell protection and proliferation. These data nourish further studies to examine the role of controlled VEGF delivery in (pre)clinical applications aimed at protecting and/or restoring the injured beta cell mass.
authors.forename: Nico
authors.initials: N
authors.lastname: De Leu
authors.forename: Yves
authors.initials: Y
authors.lastname: Heremans
authors.forename: Violette
authors.initials: V
authors.lastname: Coppens
authors.forename: Naomi
authors.initials: N
authors.lastname: Van Gassen
authors.forename: Ying
authors.initials: Y
authors.lastname: Cai
authors.forename: Joke
authors.initials: J
authors.lastname: D'Hoker
authors.forename: Judith
authors.initials: J
authors.lastname: Magenheim
authors.forename: Seth
authors.initials: S
authors.lastname: Salpeter
authors.forename: Avital
authors.initials: A
authors.lastname: Swisa
authors.forename: Abed
authors.initials: A
authors.lastname: Khalaileh
authors.forename: Carole
authors.initials: C
authors.lastname: Arnold
authors.forename: Gerard
authors.initials: G
authors.lastname: Gradwohl
authors.forename: Mark
authors.initials: M
authors.lastname: Van de Casteele
authors.forename: Eli
authors.initials: E
authors.lastname: Keshet
authors.forename: Yuval
authors.initials: Y
authors.lastname: Dor
authors.forename: Harry
authors.initials: H
authors.lastname: Heimberg
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D002470:Cell Survival / Q000502:physiology; D003920:Diabetes Mellitus / Q000378:metabolism / Q000517:prevention & control*; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000378:metabolism*; D007515:Islets of Langerhans / Q000098:blood supply / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D051381:Rats; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*
chemical_list: D042461:Vascular Endothelial Growth Factor A