Importance of gestational hypoglycaemia for foetal malformations and skeletal development in rats
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
The aim was to investigate embryo-foetal effects of continuous maternal insulin-induced hypoglycaemia extending throughout gestation or until gestation day (GD)17 (typical last day of dosing during pre-clinical evaluation) providing comparator data for safety assessment of longer-acting insulin analogues in non-diabetic rats. Pregnant rats received human insulin (HI)-infusion during gestation until either GD20 or GD17 (HI-GD20; HI-GD17). On GD20, foetal abnormalities and skeletal ossification/mineralisation were evaluated. HI-infusion induced continuous hypoglycaemia. Foetal skeletal and eye malformations (e.g. bent ribs, microphthalmia) were common in both groups. Foetal size and skeletal ossification/mineralisation decreased, particularly with infusion throughout gestation. Concluding, insulin-induced hypoglycaemia during gestation in non-diabetic rats is damaging to embryo-foetal growth and skeletal development, particularly after GD17. Three days without HI-infusion after GD17 allows for some developmental catch-up. Eye development is sensitive to HI-infusion before GD17. These results should serve as a benchmark during pre-clinical safety assessment of longer-acting insulin analogues tested in rats.
Originalsprog | Engelsk |
---|---|
Tidsskrift | Reproductive Toxicology |
Vol/bind | 91 |
Sider (fra-til) | 14-26 |
Antal sider | 13 |
ISSN | 0890-6238 |
DOI | |
Status | Udgivet - 2020 |
ID: 234210000