TIME-DEPENDENT PHYSIOLOGICAL REGULATION OF RODENT AND OVINE PLACENTALGLUCOSE-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 streptozotoci n-induced diabetic pregnancy (STZ-D), uterine artery ligation-intraute rine growth restriction (IUGR) rat models, pregnant sheep exposed to c hronic maternal glucose and insulin infusions, and the HRP.1 rat troph oblastic 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 an d ischemic hypoxia resulted in a 50% decline in placental GLUT-1 level s (P < 0.05). In late-gestation ewes, maternal and fetal hyperglycemia caused an initial threefold increase at 48 h (P < 0.05), with a persi stent decline between 10 to 21 days, whereas maternal and fetal hypogl ycemia 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 glucos e caused a 60% decline (P < 0.05; 48 h) in HRP.1 GLUT-1 levels compare d with 5 mM of glucose. The added effect of hypoxia on 0 and 100 mM gl ucose concentrations appeared to increase GLUT-1 concentrations compar ed with normoxic cells (P < 0.05; 100 mM at 18 h). We conclude that ab normal glucose concentrations alter rodent and ovine placental GLUT-1 levels in a time- and concentration-dependent manner; hypoxia may upre gulate this effect. The changes in placental GLUT-1 concentrations may contribute toward the process of altered maternoplacentofetal transpo rt of glucose, thereby regulating placental and fetal growth.