In Situ Analysis Reveals That CFTR Is Expressed in Only a Small Minority of ß-Cells in Normal Adult Human Pancreas.
J Clin Endocrinol Metab
; 105(5)2020 05 01.
Article
em En
| MEDLINE
| ID: mdl-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 ß-cell insulin secretion. Efforts toward improving the functional ß-cell deficit in cystic fibrosis-related diabetes (CFRD) have been hampered by an incomplete understanding of whether ß-cell function is intrinsically regulated by cystic fibrosis transmembrane conductance regulator (CFTR). Definitively excluding meaningful CFTR expression in human ß-cells in situ would contribute significantly to the understanding of CFRD pathogenesis. OBJECTIVE:
To determine CFTR messenger ribonucleic acid (mRNA) and protein expression within ß-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 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 ß-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.Palavras-chave
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Coleções:
01-internacional
Base de dados:
MEDLINE
Limite:
Adult
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Aged
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Animals
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article