Department of Medicine, Division of Diabetes, Diabetes Center of Excellence
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
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.
Cell Biology, Diabetes, Endocrinology, Genetic diseases, Islet cells
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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
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
Hart NJ, Babon JA, DeNicola ME, Kent SC, Powers AC. (2018). Cystic fibrosis-related diabetes is caused by islet loss and inflammation. Open Access Publications by UMMS Authors. https://doi.org/10.1172/jci.insight.98240. Retrieved from https://escholarship.umassmed.edu/oapubs/3446
Cell Biology Commons, Cellular and Molecular Physiology Commons, Congenital, Hereditary, and Neonatal Diseases and Abnormalities Commons, Endocrine System Commons, Endocrine System Diseases Commons, Endocrinology Commons, Endocrinology, Diabetes, and Metabolism Commons, Hormones, Hormone Substitutes, and Hormone Antagonists Commons, Nutritional and Metabolic Diseases Commons, Respiratory Tract Diseases Commons