title: Conditional islet hypovascularisation does not preclude beta cell expansion during pregnancy in mice.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Beta Cell Neogenesis (BENE), Vrije Universiteit Brussel, Laarbeeklaan 103, 1090, Brussels, Belgium.|Department of Paediatrics, Division of Paediatric Endocrinology, Ghent University Hospital and Ghent University, Ghent, Belgium.
authors.forename: Willem
authors.initials: W
authors.lastname: Staels
authors.affiliation: Beta Cell Neogenesis (BENE), Vrije Universiteit Brussel, Laarbeeklaan 103, 1090, Brussels, Belgium.
authors.forename: Yves
authors.initials: Y
authors.lastname: Heremans
authors.affiliation: Beta Cell Neogenesis (BENE), Vrije Universiteit Brussel, Laarbeeklaan 103, 1090, Brussels, Belgium.
authors.forename: Gunter
authors.initials: G
authors.lastname: Leuckx
authors.affiliation: Beta Cell Neogenesis (BENE), Vrije Universiteit Brussel, Laarbeeklaan 103, 1090, Brussels, Belgium.
authors.forename: Naomi
authors.initials: N
authors.lastname: Van Gassen
authors.affiliation: Beta Cell Neogenesis (BENE), Vrije Universiteit Brussel, Laarbeeklaan 103, 1090, Brussels, Belgium.
authors.forename: Ciro
authors.initials: C
authors.lastname: Salinno
authors.affiliation: Beta Cell Neogenesis (BENE), Vrije Universiteit Brussel, Laarbeeklaan 103, 1090, Brussels, Belgium.
authors.forename: Sofie
authors.initials: S
authors.lastname: De Groef
authors.affiliation: Department of Paediatrics, Division of Paediatric Endocrinology, Ghent University Hospital and Ghent University, Ghent, Belgium.
authors.forename: Martine
authors.initials: M
authors.lastname: Cools
authors.affiliation: Department of Developmental Biology and Cancer Research, Institute of Medical Research Israel-Canada, Hebrew University Hadassah Medical School, Jerusalem, Israel.
authors.forename: Eli
authors.initials: E
authors.lastname: Keshet
authors.affiliation: Department of Developmental Biology and Cancer Research, Institute of Medical Research Israel-Canada, Hebrew University Hadassah Medical School, Jerusalem, Israel.
authors.forename: Yuval
authors.initials: Y
authors.lastname: Dor
authors.affiliation: Beta Cell Neogenesis (BENE), Vrije Universiteit Brussel, Laarbeeklaan 103, 1090, Brussels, Belgium. Harry.Heimberg@vub.ac.be.
authors.forename: Harry
authors.initials: H
authors.lastname: Heimberg
authors.affiliation: Beta Cell Neogenesis (BENE), Vrije Universiteit Brussel, Laarbeeklaan 103, 1090, Brussels, Belgium. Nico.De.Leu@vub.ac.be.|Department of Endocrinology, Universitair Ziekenhuis Brussel, Brussels, Belgium. Nico.De.Leu@vub.ac.be.|Department of Endocrinology, Algemeen Stedelijk Ziekenhuis Aalst, Aalst, Belgium. Nico.De.Leu@vub.ac.be.
authors.forename: Nico
authors.initials: N
authors.lastname: De Leu
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000235:genetics / Q000502:physiology; D048429:Cell Size; D005260:Female; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D007515:Islets of Langerhans / Q000378:metabolism; D051379:Mice; D011247:Pregnancy; D051381:Rats; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics / Q000378:metabolism
chemical_list: D042461:Vascular Endothelial Growth Factor A; C501163:Flt1 protein, mouse; D040281:Vascular Endothelial Growth Factor Receptor-1
keywords: Beta cell; FLT1; Islet; Pancreas; Pregnancy; VEGF; Vascularisation