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Acta Diabetologica

Published in:

27-12-2023 | Insulins | Original Article

Downregulation of Sirt3 contributes to β-cell dedifferentiation via FoxO1 in type 2 diabetic mellitus

Authors: Yaxing Nie, Yunye Zhang, Shuqing Liu, Zhi Xu, Chunya Xia, Lei Du, Xiaoxing Yin, Jianyun Wang

Published in: Acta Diabetologica | Issue 4/2024

Abstract

Aims

FoxO1 is an important factor in the β-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 β-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 β-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 β-cell dedifferentiation and decreased function of insulin secretion under high glucose conditions. When Sirt3 was knocked down in INS1 cells, increased β-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 β-cell dedifferentiation in high glucose via FoxO1. Intervention of Sirt3 may be an effective approach to prevent β-cell failure in T2DM.

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Title: Downregulation of Sirt3 contributes to β-cell dedifferentiation via FoxO1 in type 2 diabetic mellitus
Authors: Yaxing Nie
Yunye Zhang
Shuqing Liu
Zhi Xu
Chunya Xia
Lei Du
Xiaoxing Yin
Jianyun Wang
Publication date: 27-12-2023
Publisher: Springer Milan
Keywords: Insulins
Insulins
Published in: Acta Diabetologica / Issue 4/2024
Print ISSN: 0940-5429
Electronic ISSN: 1432-5233
DOI: https://doi.org/10.1007/s00592-023-02221-w

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Abstract

Aims

Methods

Results

Conclusion

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