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Hepatic AMPK activation in response to dynamic REDOX balance is a biomarker of exercise to improve blood glucose control

Meiling Wu, Anda Zhao, Xingchen Yan, Hongyang Gao, Chunwang Zhang, Xiaomin Liu, Qiwen Luo, Feizhou Xie, Shanlin Liu, Dongyun Shi
doi: https://doi.org/10.1101/2022.05.15.491995
Meiling Wu
1Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, People’s Republic of China
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Anda Zhao
1Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, People’s Republic of China
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Xingchen Yan
1Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, People’s Republic of China
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Hongyang Gao
2Institute of Electronmicroscopy, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, People’s Republic of China
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Chunwang Zhang
1Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, People’s Republic of China
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Xiaomin Liu
1Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, People’s Republic of China
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Qiwen Luo
1Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, People’s Republic of China
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Feizhou Xie
3Changning Maternity and Infant Health Hospital, East China Normal University, Shanghai, 200032, People’s Republic of China
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Shanlin Liu
1Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, People’s Republic of China
4Free Radical Regulation and Application Research Center of Fudan University, Shanghai, 200032, People’s Republic of China
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  • For correspondence: dyshi@fudan.edu.cn slliu@shmu.edu.cn
Dongyun Shi
1Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, People’s Republic of China
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  • For correspondence: dyshi@fudan.edu.cn slliu@shmu.edu.cn
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Abstract

Antioxidant intervention is considered to inhibit reactive oxygen species (ROS) and alleviates 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 antioxidants 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 glycolysis and aerobic oxidation mediated by hepatic AMPK activation, 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, excess 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 in diabetes by promoting redox balance, despite the levels of redox balance are different. Moreover, the activation and expression of AMPK could act as a biomarker to reflect the effective treatment range for diabetes. This finding provides theoretical evidence for the precise regulation of diabetes by antioxidants and exercise.

Competing Interest Statement

The authors have declared no competing interest.

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Posted May 15, 2022.
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Hepatic AMPK activation in response to dynamic REDOX balance is a biomarker of exercise to improve blood glucose control
Meiling Wu, Anda Zhao, Xingchen Yan, Hongyang Gao, Chunwang Zhang, Xiaomin Liu, Qiwen Luo, Feizhou Xie, Shanlin Liu, Dongyun Shi
bioRxiv 2022.05.15.491995; doi: https://doi.org/10.1101/2022.05.15.491995
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Hepatic AMPK activation in response to dynamic REDOX balance is a biomarker of exercise to improve blood glucose control
Meiling Wu, Anda Zhao, Xingchen Yan, Hongyang Gao, Chunwang Zhang, Xiaomin Liu, Qiwen Luo, Feizhou Xie, Shanlin Liu, Dongyun Shi
bioRxiv 2022.05.15.491995; doi: https://doi.org/10.1101/2022.05.15.491995

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