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Insulin Inhibits Autophagy by Inhibiting the Binding of FoXO1 to the Promoter Region of GABARAPL1
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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Georg Thieme Verlag
2023
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10484641/ https://www.ncbi.nlm.nih.gov/pubmed/37380030 http://dx.doi.org/10.1055/a-2119-3301 |
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author | Hong, Tao Wen, Jie Mei, Lang Li, Ruixiang Zhou, Junlin Li, Jiaoyang Xiao, Xin-Hua |
author_facet | Hong, Tao Wen, Jie Mei, Lang Li, Ruixiang Zhou, Junlin Li, Jiaoyang Xiao, Xin-Hua |
author_sort | Hong, Tao |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-10484641 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Georg Thieme Verlag |
record_format | MEDLINE/PubMed |
spelling | pubmed-104846412023-09-08 Insulin Inhibits Autophagy by Inhibiting the Binding of FoXO1 to the Promoter Region of GABARAPL1 Hong, Tao Wen, Jie Mei, Lang Li, Ruixiang Zhou, Junlin Li, Jiaoyang Xiao, Xin-Hua Horm Metab Res 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. Georg Thieme Verlag 2023-09-07 /pmc/articles/PMC10484641/ /pubmed/37380030 http://dx.doi.org/10.1055/a-2119-3301 Text en 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/). https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License, which permits unrestricted reproduction and distribution, for non-commercial purposes only; and use and reproduction, but not distribution, of adapted material for non-commercial purposes only, provided the original work is properly cited. |
spellingShingle | Hong, Tao Wen, Jie Mei, Lang Li, Ruixiang Zhou, Junlin Li, Jiaoyang Xiao, Xin-Hua Insulin Inhibits Autophagy by Inhibiting the Binding of FoXO1 to the Promoter Region of GABARAPL1 |
title | Insulin Inhibits Autophagy by Inhibiting the Binding of FoXO1 to the
Promoter Region of GABARAPL1 |
title_full | Insulin Inhibits Autophagy by Inhibiting the Binding of FoXO1 to the
Promoter Region of GABARAPL1 |
title_fullStr | Insulin Inhibits Autophagy by Inhibiting the Binding of FoXO1 to the
Promoter Region of GABARAPL1 |
title_full_unstemmed | Insulin Inhibits Autophagy by Inhibiting the Binding of FoXO1 to the
Promoter Region of GABARAPL1 |
title_short | Insulin Inhibits Autophagy by Inhibiting the Binding of FoXO1 to the
Promoter Region of GABARAPL1 |
title_sort | insulin inhibits autophagy by inhibiting the binding of foxo1 to the
promoter region of gabarapl1 |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10484641/ https://www.ncbi.nlm.nih.gov/pubmed/37380030 http://dx.doi.org/10.1055/a-2119-3301 |
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