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Evolving Mechanistic Views and Emerging Therapeutic Strategies for Cystic Fibrosis–Related Diabetes

Diabetes is a common and important complication of cystic fibrosis, an autosomal recessive genetic disease due to mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Cystic fibrosis–related diabetes (CFRD) is associated with profound detrimental effects on the disease c...

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Detalles Bibliográficos
Autor principal: Yoon, John C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Endocrine Society 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5686691/
https://www.ncbi.nlm.nih.gov/pubmed/29264462
http://dx.doi.org/10.1210/js.2017-00362
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author Yoon, John C.
author_facet Yoon, John C.
author_sort Yoon, John C.
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description Diabetes is a common and important complication of cystic fibrosis, an autosomal recessive genetic disease due to mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Cystic fibrosis–related diabetes (CFRD) is associated with profound detrimental effects on the disease course and mortality and is expected to increase in prevalence as the survival of patients with cystic fibrosis continues to improve. Despite progress in the functional characterization of CFTR molecular defects, the mechanistic basis of CFRD is not well understood, in part because of the relative inaccessibility of the pancreatic tissue and the limited availability of representative animal models. This review presents a concise overview of the current understanding of CFRD pathogenesis and provides a cutting-edge update on novel findings from human and animal studies. Potential contributions from paracrine mechanisms and β-cell compensatory mechanisms are highlighted, as well as functional β-cell and α-cell defects, incretin defects, exocrine pancreatic insufficiency, and loss of islet cell mass. State-of-the-art and emerging treatment options are explored, including advances in insulin administration, CFTR modulators, cell replacement, gene replacement, and gene editing therapies.
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spelling pubmed-56866912017-12-20 Evolving Mechanistic Views and Emerging Therapeutic Strategies for Cystic Fibrosis–Related Diabetes Yoon, John C. J Endocr Soc Mini-review Diabetes is a common and important complication of cystic fibrosis, an autosomal recessive genetic disease due to mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Cystic fibrosis–related diabetes (CFRD) is associated with profound detrimental effects on the disease course and mortality and is expected to increase in prevalence as the survival of patients with cystic fibrosis continues to improve. Despite progress in the functional characterization of CFTR molecular defects, the mechanistic basis of CFRD is not well understood, in part because of the relative inaccessibility of the pancreatic tissue and the limited availability of representative animal models. This review presents a concise overview of the current understanding of CFRD pathogenesis and provides a cutting-edge update on novel findings from human and animal studies. Potential contributions from paracrine mechanisms and β-cell compensatory mechanisms are highlighted, as well as functional β-cell and α-cell defects, incretin defects, exocrine pancreatic insufficiency, and loss of islet cell mass. State-of-the-art and emerging treatment options are explored, including advances in insulin administration, CFTR modulators, cell replacement, gene replacement, and gene editing therapies. Endocrine Society 2017-10-30 /pmc/articles/PMC5686691/ /pubmed/29264462 http://dx.doi.org/10.1210/js.2017-00362 Text en Copyright © 2017 Endocrine Society https://creativecommons.org/licenses/by-nc-nd/4.0/ This article has been published under the terms of the Creative Commons Attribution Non-Commercial, No-Derivatives License (CC BY-NC-ND; https://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Mini-review
Yoon, John C.
Evolving Mechanistic Views and Emerging Therapeutic Strategies for Cystic Fibrosis–Related Diabetes
title Evolving Mechanistic Views and Emerging Therapeutic Strategies for Cystic Fibrosis–Related Diabetes
title_full Evolving Mechanistic Views and Emerging Therapeutic Strategies for Cystic Fibrosis–Related Diabetes
title_fullStr Evolving Mechanistic Views and Emerging Therapeutic Strategies for Cystic Fibrosis–Related Diabetes
title_full_unstemmed Evolving Mechanistic Views and Emerging Therapeutic Strategies for Cystic Fibrosis–Related Diabetes
title_short Evolving Mechanistic Views and Emerging Therapeutic Strategies for Cystic Fibrosis–Related Diabetes
title_sort evolving mechanistic views and emerging therapeutic strategies for cystic fibrosis–related diabetes
topic Mini-review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5686691/
https://www.ncbi.nlm.nih.gov/pubmed/29264462
http://dx.doi.org/10.1210/js.2017-00362
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