Importance of gestational hypoglycaemia for foetal malformations and skeletal development in rats
(2020) In Reproductive Toxicology 91. p.14-26- Abstract
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,... (More)
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.
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- author
- Jensen, Vivi Flou Hjorth LU ; Mølck, Anne Marie ; Lykkesfeldt, Jens ; Fels, Johannes Josef ; Andersen, Lene ; Renaut, Ruth ; McGuigan, Fiona LU ; Åkesson, Kristina E. LU and Bøgh, Ingrid Brück
- organization
- publishing date
- 2020
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Embryo-foetal development, Human insulin, Hypoglycaemia, Pre-clinical, Toxicology
- in
- Reproductive Toxicology
- volume
- 91
- pages
- 13 pages
- publisher
- Elsevier
- external identifiers
-
- pmid:31644949
- scopus:85074344927
- ISSN
- 0890-6238
- DOI
- 10.1016/j.reprotox.2019.10.003
- language
- English
- LU publication?
- yes
- id
- 1f90583a-49cf-4b6e-94e8-8c6cfce1f767
- date added to LUP
- 2021-01-15 10:23:07
- date last changed
- 2024-08-08 10:17:29
@article{1f90583a-49cf-4b6e-94e8-8c6cfce1f767, abstract = {{<p>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.</p>}}, author = {{Jensen, Vivi Flou Hjorth and Mølck, Anne Marie and Lykkesfeldt, Jens and Fels, Johannes Josef and Andersen, Lene and Renaut, Ruth and McGuigan, Fiona and Åkesson, Kristina E. and Bøgh, Ingrid Brück}}, issn = {{0890-6238}}, keywords = {{Embryo-foetal development; Human insulin; Hypoglycaemia; Pre-clinical; Toxicology}}, language = {{eng}}, pages = {{14--26}}, publisher = {{Elsevier}}, series = {{Reproductive Toxicology}}, title = {{Importance of gestational hypoglycaemia for foetal malformations and skeletal development in rats}}, url = {{http://dx.doi.org/10.1016/j.reprotox.2019.10.003}}, doi = {{10.1016/j.reprotox.2019.10.003}}, volume = {{91}}, year = {{2020}}, }