Conditional islet hypovascularisation does not preclude beta cell expansion during pregnancy in mice

Willem Staels, Yves Heremans, Gunter Leuckx, Naomi Van Gassen, Ciro Salinno, Sofie De Groef, Martine Cools, Eli Keshet, Yuval Dor, Harry Heimberg*, Nico De Leu

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Aims/hypothesis: Endothelial–endocrine cell interactions and vascular endothelial growth factor (VEGF)-A signalling are deemed essential for maternal islet vascularisation, glucose control and beta cell expansion during mouse pregnancy. The aim of this study was to assess whether pregnancy-associated beta cell expansion was affected under conditions of islet hypovascularisation. Methods: Soluble fms-like tyrosine kinase 1 (sFLT1), a VEGF-A decoy receptor, was conditionally overexpressed in maternal mouse beta cells from 1.5 to 14.5 days post coitum. Islet vascularisation, glycaemic control, beta cell proliferation, individual beta cell size and total beta cell volume were assessed in both pregnant mice and non-pregnant littermates. Results: Conditional overexpression of sFLT1 in beta cells resulted in islet hypovascularisation and glucose intolerance in both pregnant and non-pregnant mice. In contrast to non-pregnant littermates, glucose intolerance in pregnant mice was transient. sFLT1 overexpression did not affect pregnancy-associated changes in beta cell proliferation, individual beta cell size or total beta cell volume. Conclusions/interpretation: Reduced intra-islet VEGF-A signalling results in maternal islet hypovascularisation and impaired glycaemic control but does not preclude beta cell expansion during mouse pregnancy.

Original languageAmerican English
Pages (from-to)1051-1056
Number of pages6
JournalDiabetologia
Volume60
Issue number6
DOIs
StatePublished - 1 Jun 2017

Bibliographical note

Publisher Copyright:
© 2017, Springer-Verlag Berlin Heidelberg.

Keywords

  • Beta cell
  • FLT1
  • Islet
  • Pancreas
  • Pregnancy
  • VEGF
  • Vascularisation

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