High concentration of glucose decreases glucose transporter-1 expression in mouse placenta in vitro and in vivo

Facilitative glucose transporter-1 (GLUT1) is expressed abundantly and has an important role in glucose transfer in placentas. However, little is know n about the regulation of GLUT1 expression in placental cells. We studied t he changes in placental GLUT1 levels in relation to changes in glucose conc entration in vitvo and in vivo. In in vitvo experiments, dispersed mouse pl acental cells were incubated under control (5.5 mM) and moderately high (22 mM) glucose concentrations, and 2-deoxyglucose uptake into cells was studi ed on days 1-5 of culture. After 4 days of incubation under both conditions , GLUT1 mRNA and proten levels were examined by Northern and immunoblot ana lyses. Treatment of cells with 22 mM glucose resulted in a significant decr ease in 2-deoxyglucose uptake compared with control, from day 2 to day 5 of culture. Moreover, GLUT1 mRNA and protein levels on day 4 of culture were significantly reduced in cells incubated with 22 mM glucose compared with c ontrol. Next, we rendered mice diabetic by administering 200 mu g/g body we ight streptozotocin (STZ) on day 8 of pregnancy. Animals were killed on day 12 of pregnancy and placental tissues were obtained. [H-3]Cytochalasin B b inding study was carried out to assess total GLUTs, and GLUT1 mRNA and prot ein were measured as above. [H-3]Cytochalasin B binding sites in placentas from STZ-treated mice were significantly less than those in control mice. N orthern and immunoblot analyses revealed a significant decrease in GLUT1 mR NA and protein levels in diabetic mice compared with the controls. These fi ndings suggest that the glucose concentration may regulate the expression o f placental GLUT1.