Journal article
In Situ Analysis Reveals That CFTR Is Expressed in Only a Small Minority of beta-Cells in Normal Adult Human Pancreas
The journal of clinical endocrinology and metabolism, Vol.105(5), pp.1366-1374
05/01/2020
DOI: 10.1210/clinem/dgz209
PMCID: PMC7341165
PMID: 31748811
Abstract
Context: Although diabetes affects 40% to 50% of adults with cystic fibrosis, remarkably little is known regarding the underlying mechanisms leading to impaired pancreatic beta-cell insulin secretion. Efforts toward improving the functional beta-cell deficit in cystic fibrosis-related diabetes (CFRD) have been hampered by an incomplete understanding of whether beta-cell function is intrinsically regulated by cystic fibrosis transmembrane conductance regulator (CFTR). Definitively excluding meaningful CFTR expression in human beta-cells in situ would contribute significantly to the understanding of CFRD pathogenesis.
Objective: To determine CFTR messenger ribonucleic acid (mRNA) and protein expression within beta-cells in situ in the unmanipulated human pancreas of donors without any known pancreatic pathology.
Design: 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.
Results: 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 insulinpositive 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 beta-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.
Details
- Title: Subtitle
- In Situ Analysis Reveals That CFTR Is Expressed in Only a Small Minority of beta-Cells in Normal Adult Human Pancreas
- Creators
- Michael G. White - Newcastle Univ, Inst Cellular Med, Med Sch, Diabet Regenerat Med Res Grp, Framlington Pl, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, EnglandRashmi R. Maheshwari - Newcastle Univ, Inst Cellular Med, Med Sch, Diabet Regenerat Med Res Grp, Framlington Pl, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, EnglandScott J. Anderson - University of Newcastle AustraliaRolando Berlinguer-Palmini - Newcastle Univ, Bioimaging Unit, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, EnglandClaire Jones - Proxim (United States)Sarah J. Richardson - University of ExeterPavana G. Rotti - Univ Iowa, Fraternal Order Eagles Diabet Res Ctr, Iowa City, IA USASarah L. Armour - Newcastle Univ, Inst Cellular Med, Med Sch, Diabet Regenerat Med Res Grp, Framlington Pl, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, EnglandYuchun Ding - Newcastle Univ, Sch Comp, Interdisciplinary Comp & Complex Biosyst ICOS Res, Urban Sci Bldg,1 Sci Sq, Newcastle Upon Tyne NE4 5TG, Tyne & Wear, EnglandNatalio Krasnogor - Newcastle Univ, Sch Comp, Interdisciplinary Comp & Complex Biosyst ICOS Res, Urban Sci Bldg,1 Sci Sq, Newcastle Upon Tyne NE4 5TG, Tyne & Wear, EnglandJohn F. Engelhardt - Univ Iowa, Fraternal Order Eagles Diabet Res Ctr, Iowa City, IA USAMike A. Gray - Newcastle Univ, Fac Med Sci, Inst Cell & Mol Biosci, Epithelial Res Grp, Newcastle Upon Tyne, Tyne & Wear, EnglandNoel G. Morgan - University of ExeterJames A. M. Shaw - Newcastle Univ, Inst Cellular Med, Med Sch, Diabet Regenerat Med Res Grp, Framlington Pl, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England
- Resource Type
- Journal article
- Publication Details
- The journal of clinical endocrinology and metabolism, Vol.105(5), pp.1366-1374
- DOI
- 10.1210/clinem/dgz209
- PMID
- 31748811
- PMCID
- PMC7341165
- NLM abbreviation
- J Clin Endocrinol Metab
- ISSN
- 0021-972X
- eISSN
- 1945-7197
- Publisher
- Endocrine Soc
- Number of pages
- 9
- Grant note
- MR/R014132/1 / Medical Research Council (MRC); UK Research & Innovation (UKRI); Medical Research Council UK (MRC) SRC007 / Cystic Fibrosis Trust (Cystic Fibrosis Related Diabetes Strategic Research Centre) MR/R014132/1 / MRC; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) National Institute for Health Research Newcastle Biomedical Research Centre
- Language
- English
- Date published
- 05/01/2020
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Anatomy and Cell Biology; Radiation Oncology; Internal Medicine
- Record Identifier
- 9984284353702771
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