Glucose Transport in H441 Lung Epithelial Cells

Glucose concentration in the fluid that lines the lumen of the airways (~0.5mM) is normally lower than that of blood (5mM). This implies that glucose is actively transported out of the airway lumen. We have shown that people with hyperglycemia have increased glucose levels in airway secretions which are associated with the presence of dangerous respiratory pathogens including MRSA (Thorax 2005; 60:–764). Glucose transporters can be divided into two groups: the facilitative glucose transporters (GLUT), and the sodium/glucose co-transporters (SGLT). The aim of this study was to establish the expression, distribution and activity of glucose transporters in polarized and non-polarized human bronchiolar epithelial H441 cells. We have detected the presence of SGLT1, GLUT2 and GLUT4 transporter isoforms in this cell line by Western blotting. A greater abundance of SGLT1 protein was localized to the basolateral membrane, GLUT2 was equally distributed to the apical and basolateral membranes and the 45KDa product for GLUT4 remained predominantly within an intracellular pool. However, a 50kD product was detected in the apical and basolateral membranes which could represent a glycosylated form of GLUT4. Functional transport studies in non-polarized cells have shown that glucose transport (10 mM) is preferentially via GLUTs. When the cells are polarized facilitative transport remains the principal mechanism of glucose uptake, however, an SGLT transport component appears, predominantly on the basolateral side. These data indicate that the process of polarization activated SGLT-mediated glucose transport. We speculate that GLUT-mediated transport could be important in removing glucose from the airway lumen. Funded by the Wellcome Trust 075049/Z/04/Z