Expression of Na(+)-coupled sugar transport in HT-29 cells: modulation by glucose.

The human colon carcinoma cell line HT-29 adapted to grow in absence of glucose exhibits a typical enterocytic differentiation. In contrast, cells grown in glucose always remain undifferentiated. To investigate whether differentiated HT-29 cells express a Na(+)-dependent sugar transporter, isotopic tracer flux measurements of a non-metabolizable sugar analogue methyl alpha-D-glucoside (AMG) were undertaken. AMG accumulation in confluent monolayer of differentiated HT-29 cells was inhibited by replacement of sodium, phlorizin, phloretin, and glucose. Kinetic studies demonstrate the presence of only one Na(+)-dependent phlorizin-sensitive sugar transporter in differentiated HT-29 cells. Undifferentiated HT-29 cells cultured in the presence of glucose did not show a Na(+)-dependent AMG accumulation. As previously demonstrated for other markers of the enterocytic differentiation, this transporter has a growth-related expression. Moreover, it shares similar properties with the Na(+)-dependent glucose transport in the human fetal small intestine and colon. To demonstrate that the expression of the Na(+)-dependent sugar cotransporter can be modulated by glucose, differentiated HT-29 cells grown in glucose-free medium were switched to 25 mM glucose. In that condition the Na(+)-dependent AMG uptake was almost abolished. However, when these cells were switched back to glucose-free medium, the Na(+)-dependent AMG uptake was restored, although at a lower level. These experiments show that differentiated HT-29 cells are a good cellular model to study the regulation of the Na(+)-dependent sugar transporter.