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In situ analysis reveals that CFTR is expressed in only a small minority of β-cells in normal adult human pancreas

Lookup NU author(s): Dr Michael White, Dr Rashmi Maheshwari, Dr Scott Anderson, Dr Rolando Berlinguer PalminiORCiD, Claire Jones, Sarah Armour, Dr Yuchun Ding, Professor Natalio KrasnogorORCiD, Dr Michael Gray, Professor James Shaw



This is the authors' accepted manuscript of an article that has been published in its final definitive form by Oxford University Press, 2020.

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Context: Although diabetes affects 40-50% of adults with cystic fibrosis, remarkably little is known regarding the underlying mechanisms leading to impaired pancreatic β-cell insulin secretion. Efforts towards 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 CFTR. Definitively excluding meaningful CFTR expression in human -cells in situ would contribute significantly to the understanding of CFRD pathogenesis. Objective: To determine CFTR mRNA and protein expression within β-cells in situ in the unmanipulated human pancreas of donors without any known pancreatic pathology. Design: In situ hybridisation for CFTR mRNA expression in parallel with insulin immunohistochemical staining; and immunofluorescence co-localisation of CFTR with insulin and the ductal marker, Keratin-7, were undertaken in pancreatic tissue blocks from 10 normal adult, non-obese deceased organ donors over a wide age range (23-71 years) with quantitative image analysis. Results: CFTR mRNA was detectable in 0.45 (0.17-0.83)% (mean(range)) of insulin-positive cells. CFTR protein expression was co-localised with Keratin-7. 100% of insulin-positive cells were immunonegative for CFTR. Conclusions: 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

Publication metadata

Author(s): White MG, Maheshwari RR, Anderson SJ, Berlinguer-Palmini R, Jones C, Richardson SJ, Rotti PG, Armour SL, Ding Y, Krasnogor N, Engelhardt JF, Gray MA, Morgan NG, Shaw JAM

Publication type: Article

Publication status: Published

Journal: Journal of Clinical Endocrinology and Metabolism

Year: 2020

Volume: 105

Issue: 5

Pages: 1366-1374

Print publication date: 01/05/2020

Online publication date: 21/11/2019

Acceptance date: 15/11/2019

Date deposited: 22/11/2019

ISSN (print): 0021-972X

ISSN (electronic): 1945-7197

Publisher: Oxford University Press


DOI: 10.1210/clinem/dgz209


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Funder referenceFunder name
MR/R014132/1Medical Research Council (MRC)