Glyburide treatment in gestational diabetes is associated with increased placental glucose transporter 1 expression and higher birth weight
Author
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Paredes Díaz, Paula Andrea
Author
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Dimasuay, Kris Genelyn
Author
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Koele Schmidt, Lindsey
Author
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Jang, Brian
Author
dc.contributor.author
Barbour, Linda A.
Author
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Jansson, Thomas
Author
dc.contributor.author
Powell, Theresa L.
Admission date
dc.date.accessioned
2018-06-27T15:02:14Z
Available date
dc.date.available
2018-06-27T15:02:14Z
Publication date
dc.date.issued
2017
Cita de ítem
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Placenta, 57 (2017): 52-59
es_ES
Identifier
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10.1016/j.placenta.2017.05.016
Identifier
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https://repositorio.uchile.cl/handle/2250/149286
Abstract
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Use of glyburide in gestational diabetes (GDM) has raised concerns about fetal and neonatal side effects, including increased birth weight. Placental nutrient transport is a key determinant of fetal growth, however the effect of glyburide on placental nutrient transporters is largely unknown. We hypothesized that glyburide treatment in GDM pregnancies is associated with increased expression of nutrient transporters in the syncytiotrophoblast plasma membranes.
We collected placentas from GDM pregnancies who delivered at term and were treated with either diet modification (n = 15) or glyburide (n = 8). Syncytiotrophoblast microvillous (MVM) and basal (BM) plasma membranes were isolated and expression of glucose (glucose transporter 1; GLUT1), amino acid (sodium-coupled neutral amino acid transporter 2; SNAT2 and L-type amino acid transporter 1; LAT1) and fatty acid (fatty acid translocase; FAT/CD36, fatty acid transporter 2 and 4; FATP2, FATP4) transporters was determined by Western blot. Additionally, we determined GLUT1 expression by confocal microscopy in cultured primary human trophoblasts (PHT) after exposure to glyburide.
Birth weight was higher in the glyburide-treated group as compared to diet-treated GDM women (3764 +/- 126 g vs. 3386 +/- 75 g; p < 0.05). GLUT1 expression was increased in both MVM (+50%; p < 0.01) and BM (+75%; p < 0.01). In contrast, MVM FAT/CD36 (-65%; p = 0.01) and FATP2 (-65%; p = 0.02) protein expression was reduced in mothers treated with glyburide. Glyburide increased membrane expression of GLUT1 in a dose-dependent manner in cultured PHT.
This data is the first to show that glyburide increases GLUT1 expression in syncytiotrophoblast MVM and BM in GDM pregnancies, and may promote transplacental glucose delivery contributing to fetal overgrowth.
es_ES
Patrocinador
dc.description.sponsorship
NIH
DK89989
National Fund for Scientific and Technological Development (FONDECYT)-Chile postdoctoral grant
3170140