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Islet Interleukin-1β Immunoreactivity Is an Early Feature of Cystic Fibrosis That May Contribute to β-Cell Failure.

Citation
Hull, R. L., et al. “Islet Interleukin-1Β Immunoreactivity Is An Early Feature Of Cystic Fibrosis That May Contribute To Β-Cell Failure.”. Diabetes Care, pp. 823-830.
Center University of Washington
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Author Rebecca L Hull, Ronald L Gibson, Sharon McNamara, Gail H Deutsch, Corinne L Fligner, Charles W Frevert, Bonnie W Ramsey, Srinath Sanda
Abstract

OBJECTIVE: Cystic fibrosis-related diabetes (CFRD) is a common complication of cystic fibrosis (CF), increasing patient morbidity and mortality. Poor understanding of CFRD pathogenesis limits the development of targeted therapies to treat and/or prevent the disease. The aim of this study was to evaluate islet pathology, specifically, inflammation, amyloid deposition, and endocrine cell composition in subjects with CF with diabetes and with CF without diabetes.

RESEARCH DESIGN AND METHODS: A retrospective analysis of archived pancreas tissue collected at autopsy was conducted using pancreas tissue from subjects with CF and diabetes (CFRD) ( = 18) and CF without diabetes (CF-no DM) ( = 17). Two cohorts of control non-CF subjects were identified, each matched to CFRD and CF-no DM subjects for age, sex, and BMI (non-CF older, = 20, and non-CF younger, = 20), respectively. Immunohistochemistry was performed to assess interleukin-1β (IL-1β) and islet hormone (insulin, glucagon, somatostatin, and pancreatic polypeptide) immunoreactivity; histochemistry was performed to quantify amyloid deposition.

RESULTS: Islet IL-1β immunoreactivity was substantially increased in both CFRD and CF-no DM subjects compared with non-CF subjects and was common in young subjects with CF (≤10 years of age). In contrast, islet amyloid deposition was increased only in CFRD subjects. We also observe abnormal islet hormone immunoreactivity, characterized by increased glucagon immunoreactivity, in CF-no DM and CFRD subjects compared with non-CF subjects.

CONCLUSIONS: These findings reveal novel molecular pathways and therapeutic targets underlying islet pathology in CF subjects and may be important in developing new approaches to treat CFRD.

Year of Publication
2018
Journal
Diabetes care
Volume
41
Issue
4
Number of Pages
823-830
Date Published
12/2018
ISSN Number
1935-5548
DOI
10.2337/dc17-1387
Alternate Journal
Diabetes Care
PMID
29437698
PMCID
PMC5860832
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