Islet-intrinsic effects of CFTR mutation

Fiona N. Manderson Koivula, Neville H. McClenaghan, Alan G. S. Harper, Catriona Kelly

Research output: Contribution to journalArticle

21 Citations (Scopus)

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 arole 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 morecomplicated 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.
LanguageEnglish
Pages1350-1355
JournalDiabetologia
Volume59
Early online date31 Mar 2016
DOIs
Publication statusE-pub ahead of print - 31 Mar 2016

Fingerprint

Cystic Fibrosis Transmembrane Conductance Regulator
Cystic Fibrosis
Mutation
Insulin
Lung
Exocytosis
Insulin-Secreting Cells
Islets of Langerhans
Membrane Potentials
Comorbidity
Pancreas
Homeostasis
Parturition
Glucose

Keywords

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

Cite this

Manderson Koivula, F. N., McClenaghan, N. H., Harper, A. G. S., & Kelly, C. (2016). Islet-intrinsic effects of CFTR mutation. Diabetologia, 59, 1350-1355. https://doi.org/10.1007/s00125-016-3936-1
Manderson Koivula, Fiona N. ; McClenaghan, Neville H. ; Harper, Alan G. S. ; Kelly, Catriona. / Islet-intrinsic effects of CFTR mutation. In: Diabetologia. 2016 ; Vol. 59. pp. 1350-1355.
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Manderson Koivula, FN, McClenaghan, NH, Harper, AGS & Kelly, C 2016, 'Islet-intrinsic effects of CFTR mutation', Diabetologia, vol. 59, pp. 1350-1355. https://doi.org/10.1007/s00125-016-3936-1

Islet-intrinsic effects of CFTR mutation. / Manderson Koivula, Fiona N.; McClenaghan, Neville H.; Harper, Alan G. S.; Kelly, Catriona.

In: Diabetologia, Vol. 59, 31.03.2016, p. 1350-1355.

Research output: Contribution to journalArticle

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Manderson Koivula FN, McClenaghan NH, Harper AGS, Kelly C. Islet-intrinsic effects of CFTR mutation. Diabetologia. 2016 Mar 31;59:1350-1355. https://doi.org/10.1007/s00125-016-3936-1