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Islet Interleukin-1β Immunoreactivity Is an Early Feature of Cystic Fibrosis That May Contribute to β-Cell Failure
- Source :
- Diabetes care, vol 41, iss 4, Diabetes Care
- Publication Year :
- 2018
- Publisher :
- American Diabetes Association, 2018.
-
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) (n = 18) and CF without diabetes (CF-no DM) (n = 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, n = 20, and non-CF younger, n = 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.
- Subjects :
- Male
0301 basic medicine
Cystic Fibrosis
Endocrinology, Diabetes and Metabolism
medicine.medical_treatment
Interleukin-1beta
Medical and Health Sciences
Cystic fibrosis
Gastroenterology
Body Mass Index
Pathogenesis
Congenital
0302 clinical medicine
Insulin-Secreting Cells
Insulin
2.1 Biological and endogenous factors
Pancreatic polypeptide
Aetiology
Child
Lung
Pediatric
geography.geographical_feature_category
Diabetes
Islet
medicine.anatomical_structure
Female
Somatostatin
Pancreas
Type 2
Lung Transplantation
Adult
medicine.medical_specialty
Adolescent
030209 endocrinology & metabolism
Pancreatic Polypeptide
Glucagon
Young Adult
Endocrinology & Metabolism
03 medical and health sciences
Rare Diseases
Clinical Research
Internal medicine
Diabetes mellitus
Diabetes Mellitus
Internal Medicine
medicine
Humans
Pathophysiology/Complications
Metabolic and endocrine
Retrospective Studies
Advanced and Specialized Nursing
geography
business.industry
medicine.disease
030104 developmental biology
Diabetes Mellitus, Type 2
business
Subjects
Details
- ISSN :
- 19355548 and 01495992
- Volume :
- 41
- Database :
- OpenAIRE
- Journal :
- Diabetes Care
- Accession number :
- edsair.doi.dedup.....9a8f2a5e161ad0fe81f14483baa506d5