Replication confers ß cell immaturity.
Nat Commun
; 9(1): 485, 2018 02 02.
Article
in En
| MEDLINE
| ID: mdl-29396395
ABSTRACT
Pancreatic ß cells are highly specialized to regulate systemic glucose levels by secreting insulin. In adults, increase in ß-cell mass is limited due to brakes on cell replication. In contrast, proliferation is robust in neonatal ß cells that are functionally immature as defined by a lower set point for glucose-stimulated insulin secretion. Here we show that ß-cell proliferation and immaturity are linked by tuning expression of physiologically relevant, non-oncogenic levels of c-Myc. Adult ß cells induced to replicate adopt gene expression and metabolic profiles resembling those of immature neonatal ß that proliferate readily. We directly demonstrate that priming insulin-producing cells to enter the cell cycle promotes a functionally immature phenotype. We suggest that there exists a balance between mature functionality and the ability to expand, as the phenotypic state of the ß cell reverts to a less functional one in response to proliferative cues.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Proto-Oncogene Proteins c-myc
/
Cell Proliferation
/
Insulin-Secreting Cells
Limits:
Animals
Language:
En
Journal:
Nat Commun
Journal subject:
BIOLOGIA
/
CIENCIA
Year:
2018
Document type:
Article
Affiliation country:
United States