Transepithelial Glucose Transport and Metabolism in BeWo Choriocarcinoma Cells

Abstract

Glucose transporters in the placental, epithelial syncytiotrophoblast barrier are asymmetrically arranged (microvillous>basal), leading to the hypothesis of a rate-limiting role for the basal membrane in transepithelial transport. This is significant since the changes which have been observed in basal membrane glucose transporter expression over gestation and in conditions such as diabetes would generate changes in maternal-to-foetal glucose transport. This study was designed to test whether the basal membrane of the syncytiotrophoblast is the rate-limiting step in transepithelial transport and to investigate the effects of metabolism on transpithelial transport. In the absence of a transporting syncytiotrophoblast monolayer, the BeWo choriocarcinoma cell line, derived from trophoblast and plated on a permeable support, was used as a model since it has an asymmetric distribution of glucose transporter activity, similar to the syncytiotrophoblast. Inhibition of basal membrane glucose transport with p -chloromercuribenzene-sulfonate (p CMBS) produced a proportional change in transepithelial transport, whereas this latter parameter was relatively insensitive to inhibition of microvillous membrane glucose transporters. These data demonstrate that the basal membrane is the rate-limiting step in transepithelial glucose transport. Experiments involving stimulation and inhibition of cellular glucose consumption demonstrated that there is a single intracellular glucose pool in BeWo cells, supplying both metabolism and transcellular transport.