Cyclin D2 is sufficient to drive ß cell self-renewal and regeneration.
Cell Cycle
; 16(22): 2183-2191, 2017.
Article
in En
| MEDLINE
| ID: mdl-28763258
ABSTRACT
Diabetes results from an inadequate mass of functional ß cells, due to either ß cell loss caused by autoimmune destruction (type I diabetes) or ß cell failure in response to insulin resistance (type II diabetes). Elucidating the mechanisms that regulate ß cell mass may be key to developing new techniques that foster ß cell regeneration as a cellular therapy to treat diabetes. While previous studies concluded that cyclin D2 is required for postnatal ß cell self-renewal in mice, it is not clear if cyclin D2 is sufficient to drive ß cell self-renewal. Using transgenic mice that overexpress cyclin D2 specifically in ß cells, we show that cyclin D2 overexpression increases ß cell self-renewal post-weaning and results in increased ß cell mass. ß cells that overexpress cyclin D2 are responsive to glucose stimulation, suggesting they are functionally mature. ß cells that overexpress cyclin D2 demonstrate an enhanced regenerative capacity after injury induced by streptozotocin toxicity. To understand if cyclin D2 overexpression is sufficient to drive ß cell self-renewal, we generated a novel mouse model where cyclin D2 is only expressed in ß cells of cyclin D2-/- mice. Transgenic overexpression of cyclin D2 in cyclin D2-/- ß cells was sufficient to restore ß cell mass, maintain normoglycaemia, and improve regenerative capacity when compared with cyclin D2-/- littermates. Taken together, our results indicate that cyclin D2 is sufficient to regulate ß cell self-renewal and that manipulation of its expression could be used to enhance ß cell regeneration.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Insulin-Secreting Cells
/
Cyclin D2
Limits:
Animals
Language:
En
Journal:
Cell Cycle
Year:
2017
Type:
Article
Affiliation country:
Canada