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.
journal_name
Diabetologiajournal_title
Diabetologiaauthors
Staels W,Heremans Y,Leuckx G,Van Gassen N,Salinno C,De Groef S,Cools M,Keshet E,Dor Y,Heimberg H,De Leu Ndoi
10.1007/s00125-017-4243-1subject
Has Abstractpub_date
2017-06-01 00:00:00pages
1051-1056issue
6eissn
0012-186Xissn
1432-0428pii
10.1007/s00125-017-4243-1journal_volume
60pub_type
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