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CC BY-NC-ND 4.0 · Horm Metab Res 2023; 55(09): 634-641
DOI: 10.1055/a-2119-3301
Original Article: Endocrine Research

Insulin Inhibits Autophagy by Inhibiting the Binding of FoXO1 to the Promoter Region of GABARAPL1

Tao Hong  ‡
1   The Second Affiliated Hospital, Department of Endocrinology and Metabolism, University of South China Medical College, Hengyang, China
,
Jie Wen‡
2   The First Affiliated Hospital, Department of Endocrinology and Metabolism, University of South China Medical College, Hengyang, China
,
Lang Mei
2   The First Affiliated Hospital, Department of Endocrinology and Metabolism, University of South China Medical College, Hengyang, China
,
Ruixiang Li
2   The First Affiliated Hospital, Department of Endocrinology and Metabolism, University of South China Medical College, Hengyang, China
,
Junlin Zhou
3   The First Affiliated Hospital, Health Management Center, University of South China Medical College, Hengyang, China
,
Jiaoyang Li
2   The First Affiliated Hospital, Department of Endocrinology and Metabolism, University of South China Medical College, Hengyang, China
,
Xin-Hua Xiao
2   The First Affiliated Hospital, Department of Endocrinology and Metabolism, University of South China Medical College, Hengyang, China
› Institutsangaben Funding Information Natural Science Foundation of Hunan Province — http://dx.doi. org/10.13039/501100004735; No. 2020JJ4544; National Natural Science Foundation of China — http://dx.doi.org/10.13039/ 501100001809; No. 81870595; Health Commission of Hunan Province — http://dx.doi.org/10.13039/100017695; No. A2017011
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Erratum zu diesem Artikel:

Correction: Insulin Inhibits Autophagy by Inhibiting the Binding of FoXO1 to the Promoter Region of GABARAPL1Horm Metab Res 2023; 55(09): e3-e3
DOI: 10.1055/a-2175-8370

Abstract

Hyperinsulinemia and insulin resistance in T2D have a potent suppressive effect on hepatic autophagy, however, the underlying mechanisms remain unclear. To explore the effect of insulin on hepatic autophagy and its possible signaling pathways, HL-7702 cells were treated with insulin with or without insulin signaling inhibitors. The interaction between insulin and the promoter region of GABARAPL1 was assessed through luciferase assay and EMSA. There were significant dose-dependent decreases in the number of intracellular autophagosomes and the protein levels of GABARAPL1 and beclin1 in insulin-treated HL-7702 cells. Insulin signaling inhibitors reversed the inhibitory effect of insulin on rapamycin-induced autophagy and autophagy-related gene upregulation. Insulin blocks the binding of FoxO1 to putative insulin response elements in GABARAPL1 gene promoter, leading to the repressed transcription of GABARAPL1 gene and the suppression of hepatic autophagy. Our study identified GABARAPL1 as a novel target of insulin in suppressing hepatic autophagy.

Key words

autophagy - insulin, diabetes - forkhead box protein O1 - gamma-aminobutyric acid A receptor-associated protein-like 1 - hepatocellular carcinoma - type 2 diabetes


Publikationsverlauf

Eingereicht: 18. Januar 2023
Eingereicht: 24. Juni 2023

Angenommen nach Revision: 28. Juni 2023

Accepted Manuscript online:
28. Juni 2023

Artikel online veröffentlicht:
07. September 2023

© 2023. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).

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