Time-dependent physiological regulation of rodent and ovine placental glucose transporter (GLUT-1) protein.
To examine the in vivo and in vitro time-dependent effects of glucose on placental glucose transporter (GLUT-1) protein levels, we employed Western blot analysis using placenta from the short-term streptozotocin-induced diabetic pregnancy (STZ-D), uterine artery ligation-intrauterine growth restriction (IUGR) rat models, pregnant sheep exposed to chronic maternal glucose and insulin infusions, and the HRP.1 rat trophoblastic cell line exposed to differing concentrations of glucose. In the rat, 6 days of STZ-D with maternal and fetal hyperglycemia caused no substantive change, whereas 72 h of IUGR with fetal hypoglycemia and ischemic hypoxia resulted in a 50% decline in placental GLUT-1 levels (P < 0.05). In late-gestation ewes, maternal and fetal hyperglycemia caused an initial threefold increase at 48 h (P < 0.05), with a persistent decline between 10 to 21 days, whereas maternal and fetal hypoglycemia led to a 30-50% decline in placental GLUT-1 levels (P < 0.05). Studies in vitro demonstrated no effect of 0 mM, whereas 100 mM glucose caused a 60% decline (P < 0.05; 48 h) in HRP.1 GLUT-1 levels compared with 5 mM of glucose. The added effect of hypoxia on 0 and 100 mM glucose concentrations appeared to increase GLUT-1 concentrations compared with normoxic cells (P < 0.05; 100 mM at 18 h). We conclude that abnormal glucose concentrations alter rodent and ovine placental GLUT-1 levels in a time- and concentration-dependent manner; hypoxia may upregulate this effect. The changes in placental GLUT-1 concentrations may contribute toward the process of altered maternoplacentofetal transport of glucose, thereby regulating placental and fetal growth.
Das
U G
UG
Department of Pediatrics, University of Pittsburgh, Magee-Womens Research Institute, Pennsylvania 15213, USA.
Sadiq
H F
HF
Soares
M J
MJ
Hay
W W
WW
Devaskar
S U
SU
D000818:Animals; D001158:Arteries / Q000601:surgery; D015153:Blotting, Western; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D005260:Female; D005317:Fetal Growth Retardation / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology*; D051272:Glucose Transporter Type 1; D008026:Ligation; D009004:Monosaccharide Transport Proteins / Q000378:metabolism*; D010920:Placenta / Q000187:drug effects / Q000378:metabolism*; D011247:Pregnancy; D011254:Pregnancy in Diabetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012756:Sheep; D013997:Time Factors; D014327:Trophoblasts / Q000378:metabolism; D014599:Uterus / Q000098:blood supply
D051272:Glucose Transporter Type 1; D009004:Monosaccharide Transport Proteins; C495679:Slc2a1 protein, rat; D005947:Glucose