CF-related diabetes: new insights from ferrets

Individuals with cystic fibrosis (CF) frequently also suffer from diabetes, which worsens CF prognosis. CF is caused by mutation of the CFTR chloride channel, leading to dysfunction of several internal organs, including the pancreas. Recently, engineered ferret and pig models of CF have been developed that more closely recapitulate the disease than rodent models used previously. Olivier et al. now report on the early stages of pancreatic pathology and diabetes development in CF ferrets, which are more similar to humans than are pigs with respect to the progression of pancreatic disease after birth. The authors found early signs of abnormal insulin secretion and glucose tolerance in neonatal CF ferrets, before overt histopathological changes occurred in the pancreas. Pancreas pathology that was associated with inflammation and fibrosis progressed in the first month of life, with an age-dependent rise in blood glucose. Compared with non-CF ferrets, newborn CF ferrets had fewer large islets and, in vitro, islets from newborn CF ferrets showed abnormal glucose-responsive insulin secretion, despite high insulin content. These results suggest an intrinsic defect in islets of CF ferrets that is present at birth. Further studies could help to develop strategies for treatment or prevention of CF-related diabetes in humans.