Fig. 9.

Model for CFTR-mediated regulation of the airway glucose barrier. A: in normal airway epithelia without insulin stimulation, nutrients like glucose (red) slowly traverse the tight junction-regulated paracellular pathway (purple) while constitutive glucose transporters (blue) mediate baseline glucose metabolism and clearance from the paracellular space. Activity of CFTR (green) is normal, whereas Glut4 transporter (yellow) is stored in GSVs near the apical plasma membrane. B: airway epithelia stimulated with insulin decrease the rate of paracellular flux while simultaneously reducing the amount of glucose in the apical space through the activity of translocated Glut4 in the apical plasma membrane. C: in cystic fibrosis airway epithelia, the paracellular route is less stringent (dashed purple box) compared with normal epithelia. This results in more glucose being transported through the tight junction-mediated barrier, where the constitutive glucose transporters act to reduce the amount of glucose in the apical space. CFTR activity is reduced, effectively changing the fluid and ion balance of CF airway epithelia. D: in CF epithelia, insulin fails to activate GSV translocation, effectively reducing insulin-stimulated Glut4 activity while simultaneously allowing small molecules <10 kDa through the paracellular barrier, effectively allowing nutrient accumulation in the apical space.