Insulin deficiency is a common feature of cystic fibrosis (CF), resulting in CF-related diabetes (CFRD) in ~20% of adolescents and ~50% of adults with the disease. The clinical consequences of insulin deficiency in CF are significant – CFRD is associated with worsened CF lung disease and increased morbidity and mortality. The loss of exocrine pancreatic tissue in CF is extensive, with its destruction being initiated around/before birth and resulting in pancreatic insufficiency in 85% of CF patients. In contrast, while most studies describe some loss of β cells, islets generally survive. This suggests that enhancing endogenous insulin secretion may be a viable therapeutic strategy in CF. However, the mechanisms underlying impaired insulin release in CF are poorly understood.