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Lookup NU author(s): Professor James Shaw
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2024 The Author(s)CF-related diabetes (CFRD) is a prevalent comorbidity in people with Cystic Fibrosis (CF), significantly impacting morbidity and mortality rates. This review article critically evaluates the current understanding of CFRD molecular mechanisms, including the role of CFTR protein, oxidative stress, unfolded protein response (UPR) and intracellular communication. CFRD manifests from a complex interplay between exocrine pancreatic damage and intrinsic endocrine dysfunction, further complicated by the deleterious effects of misfolded CFTR protein on insulin secretion and action. Studies indicate that ER stress and subsequent UPR activation play critical roles in both exocrine and endocrine pancreatic cell dysfunction, contributing to β-cell loss and insulin insufficiency. Additionally, oxidative stress and altered calcium flux, exacerbated by CFTR dysfunction, impair β-cell survival and function, highlighting the significance of antioxidant pathways in CFRD pathogenesis. Emerging evidence underscores the importance of exosomal microRNAs (miRNAs) in mediating inflammatory and stress responses, offering novel insights into CFRD's molecular landscape. Despite insulin therapy remaining the cornerstone of CFRD management, the variability in response to CFTR modulators underscores the need for personalized treatment approaches. The review advocates for further research into non-CFTR therapeutic targets, emphasizing the need to address the multifaceted pathophysiology of CFRD. Understanding the intricate mechanisms underlying CFRD will pave the way for innovative treatments, moving beyond insulin therapy to target the disease's root causes and improve the quality of life for individuals with CF.
Author(s): Umashankar B, Eliasson L, Ooi CY, Kim KW, Shaw JAM, Waters SA
Publication type: Review
Publication status: Published
Journal: Journal of Cystic Fibrosis
Year: 2024
Pages: epub ahead of print
Online publication date: 18/06/2024
Acceptance date: 04/06/2024
ISSN (print): 1569-1993
ISSN (electronic): 1873-5010
Publisher: Elsevier B.V.
URL: https://doi.org/10.1016/j.jcf.2024.06.004
DOI: 10.1016/j.jcf.2024.06.004
