Downregulation of Sirt3 contributes to ß-cell dedifferentiation via FoxO1 in type 2 diabetic mellitus.
Acta Diabetol
; 61(4): 485-494, 2024 Apr.
Article
en 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.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Diabetes Mellitus Tipo 2
/
Células Secretoras de Insulina
/
Sirtuina 3
Límite:
Animals
Idioma:
En
Revista:
Acta Diabetol
Asunto de la revista:
ENDOCRINOLOGIA
Año:
2024
Tipo del documento:
Article
País de afiliación:
China