Title: In Situ Analysis Reveals That CFTR Is Expressed in Only a Small Minority of β-Cells in Normal Adult Human Pancreas.

Authors: White, Michael G; Maheshwari, Rashmi R; Anderson, Scott J; Berlinguer-Palmini, Rolando; Jones, Claire; Richardson, Sarah J; Rotti, Pavana G; Armour, Sarah L; Ding, Yuchun; Krasnogor, Natalio; Engelhardt, John F; Gray, Mike A; Morgan, Noel G; Shaw, James A M

Published In J Clin Endocrinol Metab, (2020 05 01)

Abstract: Although diabetes affects 40% to 50% of adults with cystic fibrosis, remarkably little is known regarding the underlying mechanisms leading to impaired pancreatic β-cell insulin secretion. Efforts toward improving the functional β-cell deficit in cystic fibrosis-related diabetes (CFRD) have been hampered by an incomplete understanding of whether β-cell function is intrinsically regulated by cystic fibrosis transmembrane conductance regulator (CFTR). Definitively excluding meaningful CFTR expression in human β-cells in situ would contribute significantly to the understanding of CFRD pathogenesis.To determine CFTR messenger ribonucleic acid (mRNA) and protein expression within β-cells in situ in the unmanipulated human pancreas of donors without any known pancreatic pathology.In situ hybridization for CFTR mRNA expression in parallel with insulin immunohistochemical staining and immunofluorescence co-localization of CFTR with insulin and the ductal marker, Keratin-7 (KRT7), were undertaken in pancreatic tissue blocks from 10 normal adult, nonobese deceased organ donors over a wide age range (23-71 years) with quantitative image analysis.CFTR mRNA was detectable in a mean 0.45% (range 0.17%-0.83%) of insulin-positive cells. CFTR protein expression was co-localized with KRT7. One hundred percent of insulin-positive cells were immunonegative for CFTR.For the first time, in situ CFTR mRNA expression in the unmanipulated pancreas has been shown to be present in only a very small minority (<1%) of normal adult β-cells. These data signal a need to move away from studying endocrine-intrinsic mechanisms and focus on elucidation of exocrine-endocrine interactions in human cystic fibrosis.

PubMed ID: 31748811

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