Effect of insulin on D-glucose transport by human placental brush border membranes.

We studied the effect of insulin on the uptake of D-glucose by human placental brush border membranes (BBM) in vitro. D-glucose transport through placental BBM is a Na(+)-independent transport, inhibited by 0.5 mM phloretin. Increasing the substrate concentration from 1 to 50 mM resulted in an increase in glucose uptake according to an S-shaped relationship. Hill plot analysis suggests that at least two molecules of D-glucose are transported at the same time by the carrier. Preincubation of the placental tissue with insulin for 45 min at 22 degrees C significantly enhanced the D-glucose influx into the membrane vesicles, without influencing the slope of the Hill plot. A dose-response curve of the effect of insulin revealed that although the effect was already significant at 10(-9) M, the maximal activity was reached at 10(-8) M. The influence of insulin on D-glucose uptake was present only when preincubation of the placental tissue with the hormone was performed in the presence of Mn2+. Incubation of placental tissue with 10(-8) M insulin did not influence D-glucose efflux from the BBM vesicles. Finally, direct incubation of the membranes with insulin had no effect on the glucose influx into these membrane vesicles. We conclude that insulin, at physiological concentrations, enhances glucose uptake by the BBM, and that such a regulation might contribute to the glucose homeostasis in the fetal circulation, independent of the maternal variations in glycemia.