Hart, Nathaniel J.Babon, Jenny Aurielle BDeNicola, Megan E.Kent, Sally CPowers, Alvin C.2022-08-232022-08-232018-04-192018-06-15<p>JCI Insight. 2018 Apr 19;3(8). pii: 98240. doi: 10.1172/jci.insight.98240. [Epub ahead of print] <a href="https://doi.org/10.1172/jci.insight.98240">Link to article on publisher's site</a></p>2379-3708 (Linking)10.1172/jci.insight.9824029669939https://hdl.handle.net/20.500.14038/40643<p>Full author list omitted for brevity. For the full list of authors, see article.</p>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.en-USCopyright © 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.Cell BiologyDiabetesEndocrinologyGenetic diseasesIslet cellsCell BiologyCellular and Molecular PhysiologyCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesEndocrine SystemEndocrine System DiseasesEndocrinologyEndocrinology, Diabetes, and MetabolismHormones, Hormone Substitutes, and Hormone AntagonistsNutritional and Metabolic DiseasesRespiratory Tract DiseasesJournal Articlehttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=4457&amp;context=oapubs&amp;unstamped=1https://escholarship.umassmed.edu/oapubs/344612326429oapubs/3446