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

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

Diabetologia

journal_title

Diabetologia

authors

Staels W,Heremans Y,Leuckx G,Van Gassen N,Salinno C,De Groef S,Cools M,Keshet E,Dor Y,Heimberg H,De Leu N

doi

10.1007/s00125-017-4243-1

subject

Has Abstract

pub_date

2017-06-01 00:00:00

pages

1051-1056

issue

6

eissn

0012-186X

issn

1432-0428

pii

10.1007/s00125-017-4243-1

journal_volume

60

pub_type

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