Mitochondrial complex I subunit deficiency promotes pancreatic α-cell proliferation.
Mol Metab
; 60: 101489, 2022 06.
Article
in En
| MEDLINE
| ID: mdl-35390502
ABSTRACT
OBJECTIVE:
There is strong evidence that mitochondrial DNA mutations and mitochondrial dysfunction play a role in diabetes pathogenesis. The homozygous knock-in mtDNA mutator mouse is a model of premature aging due to the accumulation of mitochondrial DNA mutations. We used this mouse model to investigate the relationship between mitochondrial subunit expression and pancreatic islet cell composition.METHODS:
Quadruple immunofluorescence was used to quantify mitochondrial subunit expression (complex I and IV) and cell composition in pancreatic islets from mitochondrial DNA mutator mice (PolgAmut/mut) and control C57BL/6 mice at 12 and 44 weeks of age.RESULTS:
Mitochondrial complex I subunit expression was decreased in islets from 12 week PolgAmut/mut mice. This complex I deficiency persisted with age and was associated with decreased insulin staining intensity at 44 weeks. Complex I deficiency was greater in α-cells compared with ß-cells in islets from 44 week PolgAmut/mut mice. Islet cell composition was normal in 12 week PolgAmut/mut mice, but the ß α cell ratio was decreased in islets from 44 week PolgAmut/mut mice. This was due to an increase in α-cell number linked to an increase in α-cell proliferation.CONCLUSION:
Complex I deficiency promotes α-cell proliferation and alters islet cell composition.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Mitochondrial Diseases
Limits:
Animals
Language:
En
Journal:
Mol Metab
Year:
2022
Document type:
Article
Affiliation country:
United kingdom