Format

Send to

Choose Destination
Diabetologia. 2016 Jul;59(7):1350-1355. doi: 10.1007/s00125-016-3936-1. Epub 2016 Mar 31.

Islet-intrinsic effects of CFTR mutation.

Author information

1
Northern Ireland Centre for Stratified Medicine, University of Ulster, C-TRIC, Altnagelvin Hospital Site, Glenshane Road, Derry/Londonderry, BT47 6SB, Northern Ireland, UK.
2
School of Biomedical Sciences, University of Ulster, Coleraine, Northern Ireland, UK.
3
Institute for Science and Technology in Medicine, Keele University, Guy Hilton Research Centre, Stoke-on-Trent, UK.
4
Northern Ireland Centre for Stratified Medicine, University of Ulster, C-TRIC, Altnagelvin Hospital Site, Glenshane Road, Derry/Londonderry, BT47 6SB, Northern Ireland, UK. c.kelly@ulster.ac.uk.

Abstract

Cystic fibrosis-related diabetes (CFRD) is the most significant extra-pulmonary comorbidity in cystic fibrosis (CF) patients, and accelerates lung decline. In addition to the traditional view that CFRD is a consequence of fibrotic destruction of the pancreas as a whole, emerging evidence may implicate a role for cystic fibrosis transmembrane-conductance regulator (CFTR) in the regulation of insulin secretion from the pancreatic islet. Impaired first-phase insulin responses and glucose homeostasis have also been reported in CF patients. CFTR expression in both human and mouse beta cells has been confirmed, and recent studies have shown differences in endocrine pancreatic morphology from birth in CF. Recent experimental evidence suggests that functional CFTR channels are required for insulin exocytosis and the regulation of membrane potential in the pancreatic beta cell, which may account for the impairments in insulin secretion observed in many CF patients. These novel insights suggest that the pathogenesis of CFRD is more complicated than originally thought, with implications for diabetes treatment and screening in the CF population. This review summarises recent emerging evidence in support of a primary role for endocrine pancreatic dysfunction in the development of CFRD. Summary • CF is an autosomal recessive disorder caused by mutations in the CFTR gene • The vast majority of morbidity and mortality in CF results from lung disease. However CFRD is the largest extra-pulmonary co-morbidity and rapidly accelerates lung decline • Recent experimental evidence shows that functional CFTR channels are required for normal patterns of first phase insulin secretion from the pancreatic beta cell • Current clinical recommendations suggest that insulin is more effective than oral glucose-lowering drugs for the treatment of CFRD. However, the emergence of CFTR corrector and potentiator drugs may offer a personalised approach to treating diabetes in the CF population.

KEYWORDS:

Beta cells; CFTR; Cystic fibrosis; Diabetes; Endocrine; Review

PMID:
27033560
PMCID:
PMC4901107
DOI:
10.1007/s00125-016-3936-1
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Springer Icon for PubMed Central
Loading ...
Support Center