Short-term overexpression of VEGF-A in mouse beta cells indirectly stimulates their proliferation and protects against diabetes

Nico De Leu, Yves Heremans, Violette Coppens, Naomi Van Gassen, Ying Cai, Joke D'Hoker, Judith Magenheim, Seth Salpeter, Avital Swisa, Abed Khalaileh, Carole Arnold, Gerard Gradwohl, Mark Van De Casteele, Eli Keshet, Yuval Dor, Henry Heimberg

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)

Abstract

AIMS/HYPOTHESIS: 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/INTERPRETATION: 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.

Original languageEnglish
Pages (from-to)140-147
Number of pages8
JournalDiabetologia
Volume57
Issue number1
DOIs
Publication statusPublished - Jan 2014

Keywords

  • Animals
  • Cell Proliferation
  • Cell Survival/physiology
  • Diabetes Mellitus/metabolism
  • Insulin-Secreting Cells/cytology
  • Islets of Langerhans/blood supply
  • Mice
  • Mice, Transgenic
  • Rats
  • Vascular Endothelial Growth Factor A/genetics

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