Islet Interleukin-1ß Immunoreactivity Is an Early Feature of Cystic Fibrosis That May Contribute to ß-Cell Failure.
Diabetes Care
; 41(4): 823-830, 2018 04.
Article
in En
| MEDLINE
| ID: mdl-29437698
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 ANDMETHODS:
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-1ß (IL-1ß) and islet hormone (insulin, glucagon, somatostatin, and pancreatic polypeptide) immunoreactivity; histochemistry was performed to quantify amyloid deposition.RESULTS:
Islet IL-1ß 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.
Full text:
1
Collection:
01-internacional
Health context:
6_ODS3_enfermedades_notrasmisibles
Database:
MEDLINE
Main subject:
Cystic Fibrosis
/
Insulin-Secreting Cells
/
Interleukin-1beta
Type of study:
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limits:
Adolescent
/
Adult
/
Child
/
Female
/
Humans
/
Male
Language:
En
Journal:
Diabetes Care
Year:
2018
Document type:
Article