Is cystic fibrosis-related diabetes an apoptotic consequence of ER stress in pancreatic cells?

Research output: Contribution to journalArticlepeer-review

27 Citations (Scopus)

Abstract

Cystic fibrosis-related diabetes (CFRD) has emerged in the last thirty years as a critical complication of cystic fibrosis (CF) and is present in about 15% of CF patients with increasing prevalence with age approaching 50 for over 30 year olds. The mechanism of diabetes development in this group of patients is not very well defined but it seems to involve pancreatic insufficiency and loss of β-cells in the pancreas. I propose that loss of β-cell mass and thus the development of diabetes in CF patients is likely due to an apoptotic mechanism in pancreatic β-cells resulting from chronic endoplasmic reticulum stress due to the presence of malfolded CFTR in islet cells. The proposed mechanism is supported by several pieces of evidence including: (1) the absolute essentiality of an intact unfolded protein response (UPR) machinery for survival of pancreatic β-cells, (2) the high susceptibility of β-cells to prolonged ER stress leading to induction of pro-apoptotic factors and apoptosis pathways in β-cells, (3) CF patients with mutations in CFTR gene that are engaging the ER quality control system (ERAD) and hence UPR signalling are twenty time more likely to develop diabetes than those with other types of CF-causing mutations, and (4) the high levels of CFTR gene expression in pancreatic islet cells. Establishing the exact mechanism underlying the development of diabetes in CF patients is likely to have positive implications for the treatment and the development of prevention strategies of this condition. Furthermore, this paper offers a testable hypothesis to enhance our understanding of the mechanism of CFRD.

Original languageEnglish
Pages (from-to)55-57
Number of pages3
JournalMedical Hypotheses
Volume72
Issue number1
DOIs
Publication statusPublished - Jan 2009

ASJC Scopus subject areas

  • General Medicine

Fingerprint

Dive into the research topics of 'Is cystic fibrosis-related diabetes an apoptotic consequence of ER stress in pancreatic cells?'. Together they form a unique fingerprint.

Cite this