OVEREXPRESSION OF GLUT3 PLACENTAL GLUCOSE-TRANSPORTER IN DIABETIC RATS

The localization of the two major placental glucose transporter isofor ms, GLUT1 and GLUT3 was studied in 20-d pregnant rats. Immunocytochemi cal studies revealed that GLUT1 protein is expressed ubiquitously in t he junctional zone (maternal side) and the labyrinthine zone (fetal si de) of the placenta. In contrast, expression of GLUT3 protein is restr icted to the labyrinthine zone, specialized in nutrient transfer. Afte r 19-d maternal insulinopenic diabetes (streptozotocin), placental GLU T3 mRNA and protein levels were increased four-to-fivefold compared to nondiabetic rats, whereas GLUT1 mRNA and protein levels remained unmo dified, Placental 2-deoxyglucose uptake and glycogen concentration wer e also increased fivefold in diabetic rats, These data suggest that GL UT3 plays a major role in placental glucose uptake and metabolism. The role of hyperglycemia in the regulation of GLUT3 expression was asses sed by lowering the glycemia of diabetic pregnant rats, After a 5-d ph lorizin infusion to pregnant diabetic rats, placental GLUT3 mRNA and p rotein levels returned to levels similar to those observed in nondiabe tic rats. Furthermore, a short-term hyperglycemia (12 h), achieved by performing hyperglycemic clamps induced a fourfold increase in placent al GLUT3 mRNA and protein with no concomitant change in GLUT1 expressi on. This study provides the first evidence that placental GLUT3 mRNA a nd protein expression can be stimulated in vivo under hyperglycemic co nditions. Thus, GLUT3 transporter isoform appears to be highly sensiti ve to ambient glucose levels and may play a pivotal role in the severe alterations of placental function observed diabetic pregnancies.