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Hepatic AMPK signaling dynamic activation in response to REDOX balance are sentinel biomarkers of exercise and antioxidant intervention to improve blood glucose control

Antioxidant intervention is considered to inhibit reactive oxygen species (ROS) and alleviate hyperglycemia. Paradoxically, moderate exercise can produce ROS to improve diabetes. The exact redox mechanism of these two different approaches remains largely unclear. Here, by comparing exercise and anti...

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Autores principales: Wu, Meiling, Zhao, Anda, Yan, Xingchen, Gao, Hongyang, Zhang, Chunwang, Liu, Xiaomin, Luo, Qiwen, Xie, Feizhou, Liu, Shanlin, Shi, Dongyun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9645808/
https://www.ncbi.nlm.nih.gov/pubmed/36155132
http://dx.doi.org/10.7554/eLife.79939
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author Wu, Meiling
Zhao, Anda
Yan, Xingchen
Gao, Hongyang
Zhang, Chunwang
Liu, Xiaomin
Luo, Qiwen
Xie, Feizhou
Liu, Shanlin
Shi, Dongyun
author_facet Wu, Meiling
Zhao, Anda
Yan, Xingchen
Gao, Hongyang
Zhang, Chunwang
Liu, Xiaomin
Luo, Qiwen
Xie, Feizhou
Liu, Shanlin
Shi, Dongyun
author_sort Wu, Meiling
collection PubMed
description Antioxidant intervention is considered to inhibit reactive oxygen species (ROS) and alleviate hyperglycemia. Paradoxically, moderate exercise can produce ROS to improve diabetes. The exact redox mechanism of these two different approaches remains largely unclear. Here, by comparing exercise and antioxidant intervention on type 2 diabetic rats, we found moderate exercise upregulated compensatory antioxidant capability and reached a higher level of redox balance in the liver. In contrast, antioxidant intervention achieved a low-level redox balance by inhibiting oxidative stress. Both of these two interventions could promote glucose catabolism and inhibit gluconeogenesis through activation of hepatic AMP-activated protein kinase (AMPK) signaling; therefore, ameliorating diabetes. During exercise, different levels of ROS generated by exercise have differential regulations on the activity and expression of hepatic AMPK. Moderate exercise-derived ROS promoted hepatic AMPK glutathionylation activation. However, excessive exercise increased oxidative damage and inhibited the activity and expression of AMPK. Overall, our results illustrate that both exercise and antioxidant intervention improve blood glucose control in diabetes by promoting redox balance, despite different levels of redox state(s). These results indicate that the AMPK signaling activation, combined with oxidative damage markers, could act as sentinel biomarkers, reflecting the threshold of redox balance that is linked to effective glucose control in diabetes. These findings provide theoretical evidence for the precise management of diabetes by antioxidants and exercise.
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spelling pubmed-96458082022-11-15 Hepatic AMPK signaling dynamic activation in response to REDOX balance are sentinel biomarkers of exercise and antioxidant intervention to improve blood glucose control Wu, Meiling Zhao, Anda Yan, Xingchen Gao, Hongyang Zhang, Chunwang Liu, Xiaomin Luo, Qiwen Xie, Feizhou Liu, Shanlin Shi, Dongyun eLife Biochemistry and Chemical Biology Antioxidant intervention is considered to inhibit reactive oxygen species (ROS) and alleviate hyperglycemia. Paradoxically, moderate exercise can produce ROS to improve diabetes. The exact redox mechanism of these two different approaches remains largely unclear. Here, by comparing exercise and antioxidant intervention on type 2 diabetic rats, we found moderate exercise upregulated compensatory antioxidant capability and reached a higher level of redox balance in the liver. In contrast, antioxidant intervention achieved a low-level redox balance by inhibiting oxidative stress. Both of these two interventions could promote glucose catabolism and inhibit gluconeogenesis through activation of hepatic AMP-activated protein kinase (AMPK) signaling; therefore, ameliorating diabetes. During exercise, different levels of ROS generated by exercise have differential regulations on the activity and expression of hepatic AMPK. Moderate exercise-derived ROS promoted hepatic AMPK glutathionylation activation. However, excessive exercise increased oxidative damage and inhibited the activity and expression of AMPK. Overall, our results illustrate that both exercise and antioxidant intervention improve blood glucose control in diabetes by promoting redox balance, despite different levels of redox state(s). These results indicate that the AMPK signaling activation, combined with oxidative damage markers, could act as sentinel biomarkers, reflecting the threshold of redox balance that is linked to effective glucose control in diabetes. These findings provide theoretical evidence for the precise management of diabetes by antioxidants and exercise. eLife Sciences Publications, Ltd 2022-09-26 /pmc/articles/PMC9645808/ /pubmed/36155132 http://dx.doi.org/10.7554/eLife.79939 Text en © 2022, Wu, Zhao, Yan et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Biochemistry and Chemical Biology
Wu, Meiling
Zhao, Anda
Yan, Xingchen
Gao, Hongyang
Zhang, Chunwang
Liu, Xiaomin
Luo, Qiwen
Xie, Feizhou
Liu, Shanlin
Shi, Dongyun
Hepatic AMPK signaling dynamic activation in response to REDOX balance are sentinel biomarkers of exercise and antioxidant intervention to improve blood glucose control
title Hepatic AMPK signaling dynamic activation in response to REDOX balance are sentinel biomarkers of exercise and antioxidant intervention to improve blood glucose control
title_full Hepatic AMPK signaling dynamic activation in response to REDOX balance are sentinel biomarkers of exercise and antioxidant intervention to improve blood glucose control
title_fullStr Hepatic AMPK signaling dynamic activation in response to REDOX balance are sentinel biomarkers of exercise and antioxidant intervention to improve blood glucose control
title_full_unstemmed Hepatic AMPK signaling dynamic activation in response to REDOX balance are sentinel biomarkers of exercise and antioxidant intervention to improve blood glucose control
title_short Hepatic AMPK signaling dynamic activation in response to REDOX balance are sentinel biomarkers of exercise and antioxidant intervention to improve blood glucose control
title_sort hepatic ampk signaling dynamic activation in response to redox balance are sentinel biomarkers of exercise and antioxidant intervention to improve blood glucose control
topic Biochemistry and Chemical Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9645808/
https://www.ncbi.nlm.nih.gov/pubmed/36155132
http://dx.doi.org/10.7554/eLife.79939
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