Transepithelial glucose transport and metabolism in H441 human airway epithelial cells

Abstract

Increased airway glucose is associated with increased risk of lung infection. The aim of this study was to characterise transepithelial glucose transport and metabolism in a model of human airway epithelial cells. Transepithelial transport of glucose from the basolateral compartment (B) to the apical compartment (A) or from A to B was traced using 3H‐D‐glucose or non‐metabolizable 14C‐L‐glucose. More apical radiolabel accumulated (B to A) than basolateral (A to B) with 5mM 3H‐D‐glucose (0.103 ± 0.013 μmoles and 0.04 ± 0.01 μmoles per hour cm−2 p < 0.05, n = 4 respectively). Apical (B to A) and basolateral (A to B) radiolabel accumulation was similar with 5mM 14C‐L‐glucose (0.03 ± 0.01 μmoles per hour cm‐2 and 0.03 ± 0.02 μmoles per hour cm‐2 respectively). However, HPLC analysis revealed that transepithelial apical glucose accumulation (B to A) was significantly less with 5mM D‐glucose (0.01 ± 0.02 μmoles per hour cm‐2) compared to 5mM L‐glucose (0.16 ± 0.05 μmoles per hour cm‐2, p<0.05, n = 4). To try and account for this discrepancy we used proton NMR and identified metabolites formed from D‐glucose such as lactate, alanine, acetate and scyllo‐inositol (a phospholipid precursor) in the apical chamber. These data indicate that transepithelial transport and apical accumulation of glucose in the lung epithelium is reduced by intracellular metabolism and the production and release of glucose metabolites. Funded by Wellcome.