Figure 1.

Fixed versus CFTR (cystic fibrosis transmembrane conductance regulator)-reversible pathology contributing to CF-related diabetes. (A) Timeline of irreversible pathology contributing to CF-related diabetes. Exocrine pancreatic damage begins in utero, such that by 1–4 years of age most individuals with CF have developed pancreatic insufficiency. The endocrine pancreas survives, albeit in a remodeled state surrounded by an abnormal environment. (B) Restoration of CFTR function might reduce pancreatic inflammation and thus improve β-cell function. Likewise, restoration of CFTR action in the gut might improve incretin secretion and thus enhance β-cell function. Alternatively, enhancement of CFTR function in pancreas ductal epithelium might restore a paracrine environment conducive to β-cell function. Not shown are various potential mechanisms by which ivacaftor might improve glycemia by improving insulin sensitivity in CF.