Figure 8. Proposed mechanisms controlling glucose concentrations in airway surface liquid.

Normal airway: Under normal conditions, glucose predominantly diffuses from blood/interstitial fluid across the respiratory epithelium into airway surface liquid (ASL) via paracellular pathways and this is limited by the permeability of the epithelium. Apical and basolateral facilitative GLUT-mediated transport restricts glucose accumulation in ASL (there is little evidence for Na⁺-glucose co-transport in these airway cells). Glucose taken up into the cell is rapidly metabolised. This is critical to maintain low intracellular glucose concentrations which provide a driving force for glucose uptake via GLUT transporters. It also limits the transcellular transport of glucose and predicts that ASL glucose concentrations equilibrate with intracellular glucose concentration. Airway treated with pro-inflammatory mediators: Pro-inflammatory mediators reduce transepithelial resistance and increase paracellular diffusion of glucose across the epithelium into ASL. Whilst apical GLUT-mediated glucose transport and GLUT2 and 10 abundance is increased, this is insufficient to prevent a rise in glucose concentration in the ASL.