Expression of the gene encoding the high-Km glucose transporter 2 by the early postimplantation mouse embryo is essential for neural tube defects associated with diabetic embryopathy.

Détails

ID Serval
serval:BIB_21E6655D5012
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Expression of the gene encoding the high-Km glucose transporter 2 by the early postimplantation mouse embryo is essential for neural tube defects associated with diabetic embryopathy.
Périodique
Diabetologia
Auteur(s)
Li R., Thorens B., Loeken M.R.
ISSN
0012-186X[print], 0012-186X[linking]
Statut éditorial
Publié
Date de publication
2007
Peer-reviewed
Oui
Volume
50
Numéro
3
Pages
682-689
Langue
anglais
Résumé
AIMS/HYPOTHESIS: Excess glucose transport to embryos during diabetic pregnancy causes congenital malformations. The early postimplantation embryo expresses the gene encoding the high-Km GLUT2 (also known as SLC2A2) glucose transporter. The hypothesis tested here is that high-Km glucose transport by GLUT2 causes malformations resulting from maternal hyperglycaemia during diabetic pregnancy. MATERIALS AND METHODS: Glut2 mRNA was assayed by RT-PCR. The Km of embryo glucose transport was determined by measuring 0.5-20 mmol/l 2-deoxy[3H]glucose transport. To test whether the GLUT2 transporter is required for neural tube defects resulting from maternal hyperglycaemia, Glut2+/- mice were crossed and transient hyperglycaemia was induced by glucose injection on day 7.5 of pregnancy. Embryos were recovered on day 10.5, and the incidence of neural tube defects in wild-type, Glut2+/- and Glut2-/- embryos was scored. RESULTS: Early postimplantation embryos expressed Glut2, and expression was unaffected by maternal diabetes. Moreover, glucose transport by these embryos showed Michaelis-Menten kinetics of 16.19 mmol/l, consistent with transport mediated by GLUT2. In pregnancies made hyperglycaemic on day 7.5, neural tube defects were significantly increased in wild-type embryos, but Glut2+/- embryos were partially protected from neural tube defects, and Glut2-/- embryos were completely protected from these defects. The frequency of occurrence of wild-type, Glut2+/- and Glut2-/- embryos suggests that the presence of Glut2 alleles confers a survival advantage in embryos before day 10.5. CONCLUSIONS/INTERPRETATIONS: High-Km glucose transport by the GLUT2 glucose transporter during organogenesis is responsible for the embryopathic effects of maternal diabetes.
Mots-clé
Animals, Biological Transport, Crosses, Genetic, Deoxyglucose/metabolism, Diabetes Mellitus/genetics, Embryonic Development, Female, Gene Expression Regulation, Developmental, Glucose Transporter Type 2/genetics, Glucose Transporter Type 2/metabolism, Kinetics, Male, Mice, Neural Tube Defects/genetics, Pregnancy, RNA, Messenger/genetics, Reverse Transcriptase Polymerase Chain Reaction
Pubmed
Web of science
Open Access
Oui
Création de la notice
24/01/2008 13:41
Dernière modification de la notice
20/08/2019 12:58
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