Downregulation of Sirt3 contributes to ß-cell dedifferentiation via FoxO1 in type 2 diabetic mellitus.
Acta Diabetol
; 61(4): 485-494, 2024 Apr.
Article
in En
| MEDLINE
| ID: mdl-38150004
ABSTRACT
AIMS:
FoxO1 is an important factor in the ß-cell differentiation in type 2 diabetes mellitus (T2DM). Sirt3 is found to be involved in FoxO1 function. This study investigated the role of Sirt3 in the ß-cell dedifferentiation and its mechanism.METHODS:
Twelve-week-old db/db mice and INS1 cells transfected with Sirt3-specific short hairpin RNA (shSirt3) were used to evaluate the dedifferentiation of ß-cell. Insulin levels were measured by enzyme linked immunosorbent assay. The proteins of Sirt3, T-FoxO1, Ac-FoxO1 and differentiation indexes such as NGN3, OCT4, MAFA were determined by western blot or immunofluorescence staining. The combination of Sirt3 and FoxO1 was determined by the co-immunoprecipitation assay. The transcriptional activity of FoxO1 was detected by dual luciferase reporter assay.RESULTS:
Both the in vivo and in vitro results showed that Sirt3 was decreased along with ß-cell dedifferentiation and decreased function of insulin secretion under high glucose conditions. When Sirt3 was knocked down in INS1 cells, increased ß-cell dedifferentiation and lowered insulin secretion were observed. This effect was closely related to the amount loss and the decreased deacetylation of FoxO1, which resulted in a reduction in transcriptional activity.CONCLUSION:
Downregulation of Sirt3 contributes to ß-cell dedifferentiation in high glucose via FoxO1. Intervention of Sirt3 may be an effective approach to prevent ß-cell failure in T2DM.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Diabetes Mellitus, Type 2
/
Insulin-Secreting Cells
/
Sirtuin 3
Limits:
Animals
Language:
En
Journal:
Acta Diabetol
Journal subject:
ENDOCRINOLOGIA
Year:
2024
Document type:
Article
Affiliation country:
China