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Hahn, T; Barth, S; Weiss, U; Mosgoeller, W; Desoye, G.
Sustained hyperglycemia in vitro down-regulates the GLUT1 glucose transport system of cultured human term placental trophoblast: a mechanism to protect fetal development?
FASEB J 1998 12: 1221-1231. Doi: 10.1096/fasebj.12.12.1221 [OPEN ACCESS]
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Leading authors Med Uni Graz
Hahn Tom
Co-authors Med Uni Graz
Barth Sonja
Desoye Gernot
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Abstract:
The trophoblast of human placenta is directly exposed to the maternal circulation. It forms the main barrier to maternal-fetal glucose transport. The present study investigated the effect of sustained hyperglycemia in vitro on the glucose transport system of these cells. Trophoblasts isolated from term placentas and immunopurified were cultured for 24, 48, and 96 h in DMEM containing either 5.5 (normoglycemia) or 25 mmol/l D-glucose (hyperglycemia), respectively. Initial uptake of glucose was measured using 3-O-[14C]methyl-D-glucose. Kinetic parameters were calculated as K(M) = 73 mmol/l and Vmax = 29 fmol s(-1) per trophoblast cell. Uptake rates of cells cultured under hyperglycemic conditions did not differ at exogenous D-glucose concentrations in the physiological range (1, 5.5, 10, and 15 mmol/l), but were significantly decreased by 25% (P<0.05) at diabetes-like concentrations (20 and 25 mmol/l) as compared to normoglycemic conditions. This effect was due to a decrease in Vmax (-50%), whereas K(M) remained virtually unaffected. GLUT1 mRNA levels were lower by 50% (P<0.05; Northern blotting) and GLUT1 protein was reduced by 16% (P<0.05; Western blotting) in trophoblast cells cultured under hyperglycemic vs. normoglycemic conditions. We conclude that prolonged hyperglycemia in vitro reduces trophoblast glucose uptake at substrate concentrations corresponding to blood levels of poorly controlled diabetic gravidas. This effect is due to diminished GLUT1 mRNA and protein expression in the trophoblast.
Find related publications in this database (using NLM MeSH Indexing)
3-O-Methylglucose - metabolism
Biological Transport - metabolism
Cell Survival - metabolism
Cells, Cultured - metabolism
Embryonic and Fetal Development - physiology
Female - physiology
Glucose - metabolism
Glucose Transporter Type 1 - metabolism
Humans - metabolism
Hyperglycemia - metabolism
Kinetics - metabolism
Microvilli - ultrastructure
Monosaccharide Transport Proteins - biosynthesis
Pregnancy - biosynthesis
RNA, Messenger - biosynthesis
Time Factors - biosynthesis
Transcription, Genetic - biosynthesis
Trophoblasts - cytology

Find related publications in this database (Keywords)
Placenta
Glucose
Transport
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