UMMS Affiliation

Department of Medicine, Division of Diabetes, Diabetes Center of Excellence

Publication Date

2018-04-19

Document Type

Article

Disciplines

Cell Biology | Cellular and Molecular Physiology | Congenital, Hereditary, and Neonatal Diseases and Abnormalities | Endocrine System | Endocrine System Diseases | Endocrinology | Endocrinology, Diabetes, and Metabolism | Hormones, Hormone Substitutes, and Hormone Antagonists | Nutritional and Metabolic Diseases | Respiratory Tract Diseases

Abstract

Cystic fibrosis-related (CF-related) diabetes (CFRD) is an increasingly common and devastating comorbidity of CF, affecting approximately 35% of adults with CF. However, the underlying causes of CFRD are unclear. Here, we examined cystic fibrosis transmembrane conductance regulator (CFTR) islet expression and whether the CFTR participates in islet endocrine cell function using murine models of beta cell CFTR deletion and normal and CF human pancreas and islets. Specific deletion of CFTR from murine beta cells did not affect beta cell function. In human islets, CFTR mRNA was minimally expressed, and CFTR protein and electrical activity were not detected. Isolated CF/CFRD islets demonstrated appropriate insulin and glucagon secretion, with few changes in key islet-regulatory transcripts. Furthermore, approximately 65% of beta cell area was lost in CF donors, compounded by pancreatic remodeling and immune infiltration of the islet. These results indicate that CFRD is caused by beta cell loss and intraislet inflammation in the setting of a complex pleiotropic disease and not by intrinsic islet dysfunction from CFTR mutation.

Keywords

Cell Biology, Diabetes, Endocrinology, Genetic diseases, Islet cells

Rights and Permissions

Copyright © 2018, American Society for Clinical Investigation. Publisher pdf posted as allowed by the publisher's open access policy at https://insight.jci.org/kiosks/terms.

DOI of Published Version

10.1172/jci.insight.98240

Source

JCI Insight. 2018 Apr 19;3(8). pii: 98240. doi: 10.1172/jci.insight.98240. [Epub ahead of print] Link to article on publisher's site

Journal/Book/Conference Title

JCI insight

Comments

Full author list omitted for brevity. For the full list of authors, see article.

Related Resources

Link to Article in PubMed

PubMed ID

29669939

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