Willem Staels1,2, Yves Heremans1, Gunter Leuckx1, Naomi Van Gassen1, Ciro Salinno1, Sofie De Groef1, Martine Cools2, Eli Keshet3, Yuval Dor3, Harry Heimberg4, Nico De Leu5,6,7. 1. Beta Cell Neogenesis (BENE), Vrije Universiteit Brussel, Laarbeeklaan 103, 1090, Brussels, Belgium. 2. Department of Paediatrics, Division of Paediatric Endocrinology, Ghent University Hospital and Ghent University, Ghent, Belgium. 3. Department of Developmental Biology and Cancer Research, Institute of Medical Research Israel-Canada, Hebrew University Hadassah Medical School, Jerusalem, Israel. 4. Beta Cell Neogenesis (BENE), Vrije Universiteit Brussel, Laarbeeklaan 103, 1090, Brussels, Belgium. Harry.Heimberg@vub.ac.be. 5. Beta Cell Neogenesis (BENE), Vrije Universiteit Brussel, Laarbeeklaan 103, 1090, Brussels, Belgium. Nico.De.Leu@vub.ac.be. 6. Department of Endocrinology, Universitair Ziekenhuis Brussel, Brussels, Belgium. Nico.De.Leu@vub.ac.be. 7. Department of Endocrinology, Algemeen Stedelijk Ziekenhuis Aalst, Aalst, Belgium. Nico.De.Leu@vub.ac.be.
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.
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.
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