Glycaemic regulation of glucose transporter expression and activity in the human placenta.
To determine whether the expression and activity of glucose transporters in human trophoblast are regulated by glucose, syncytiotrophoblast cells, choriocarcinoma cells, and villous fragments were incubated with a range of glucose concentrations (0-20 mM, 24 h). Expression of GLUT1 and GLUT3 glucose transporters was measured by immunoblotting, while glucose transporter activity was determined by [3H]2-deoxyglucose uptake in the cultured cells. GLUT1 expression in syncytial cells was enhanced following incubation in absence of glucose, reduced by incubation in 20 mM glucose but was not altered by incubation at 1 or 12 mM glucose. Transporter activity was inversely related to extracellular glucose over the entire range of concentrations tested (0-20 mM). Incubation of villous fragments in 20 mM glucose produced a limited suppression of GLUT1 expression, but no effects were noted following incubation at 0 or 1 mM glucose. Neither GLUT1 expression in JAr and JEG-3 choriocarcinoma cells nor transport activity in JEG-3 cells was affected by extracellular glucose concentration. Unlike syncytial cells, JAr, JEG-3 and BeWo all expressed GLUT3 protein in addition to GLUT1. These results show that while syncytiotrophoblast GLUT1 expression is altered at the extremes of extracellular glucose concentration, it is refractory to glucose alone at lower concentrations. By contrast, an inverse relationship exists between glucose transporter activity and extracellular glucose. This suggests that there are post-translational regulatory mechanisms which may respond to changes in extracellular glucose concentration.
Department of Obstetrics and Gynecology, UMDNJ-New Jersey Medical School, Newark 07103-2714, USA. illsleni@umdnj.edu
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Illsley
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Sellers
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Wright
D000328:Adult; D015153:Blotting, Western; D002460:Cell Line; D002478:Cells, Cultured; D002822:Choriocarcinoma / Q000378:metabolism; D003847:Deoxyglucose / Q000378:metabolism; D005260:Female; D005947:Glucose / Q000494:pharmacology*; D051272:Glucose Transporter Type 1; D051274:Glucose Transporter Type 3; D006801:Humans; D009004:Monosaccharide Transport Proteins / Q000378:metabolism*; D009419:Nerve Tissue Proteins; D010920:Placenta / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011247:Pregnancy; D014407:Tumor Cells, Cultured
D051272:Glucose Transporter Type 1; D051274:Glucose Transporter Type 3; D009004:Monosaccharide Transport Proteins; D009419:Nerve Tissue Proteins; C495677:SLC2A1 protein, human; C495687:SLC2A3 protein, human; D003847:Deoxyglucose; D005947:Glucose