Abstract
Mitochondria serve as sensors of energy regulation and glucose levels, which are impaired by diabetes progression. Catalpol is an iridoid glycoside that exerts a hypoglycemic effect by improving mitochondrial function, but the underlying mechanism has not been fully elucidated. In the current study we explored the effects of catalpol on mitochondrial function in db/db mice and C2C12 myotubes in vitro. After oral administration of catalpol (200 mg·kg−1·d−1) for 8 weeks, db/db mice exhibited a decreased fasting blood glucose level and restored mitochondrial function in skeletal muscle. Catalpol increased mitochondrial biogenesis, evidenced by significant elevations in the number of mitochondria, mitochondrial DNA levels, and the expression of three genes associated with mitochondrial biogenesis: peroxisome proliferator-activated receptor gammaco-activator 1 (PGC-1α), mitochondrial transcription factor A (TFAM) and nuclear respiratory factor 1 (NRF1). In C2C12 myotubes, catalpol significantly increased glucose uptake and ATP production. These effects depended on activation of AMP-activated protein kinase (AMPK)-mediated mitochondrial biogenesis. Thus, catalpol improves skeletal muscle mitochondrial function by activating AMPK-mediated mitochondrial biogenesis. These findings may guide the development of a new therapeutic approach for type 2 diabetes.
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Acknowledgements
This work was supported by grants from the National Natural Science Foundation of China (No. 81403154, 81773827, 81573514, 81773995, 81873084, 81573690); the Scholar of the 14th Batch of “Six Talents Peak” High-level Talent Selection program (SWYY-094); the Postgraduate Research Practice Innovation Program of Jiangsu Province (KYCX19-0763); the “Double First-Class” University project (CPU2018GY33); the Qinghai Province High-End Innovative Thousand Talents Program; and the Tianshan Cedar Project of the Xinjiang Uygur Autonomous Region (2018XS21).
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DQX and LW analyzed the data, contributed to discussions and wrote the manuscript. DQX, CJL, and SSF collected the data. ZJL and HFH analyzed the data. LXS reviewed the manuscript. TW and ZZJ conceived the experiments, analyzed the data and edited/reviewed the manuscript. LYZ is the guarantor of this work, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
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Xu, Dq., Li, Cj., Jiang, Zz. et al. The hypoglycemic mechanism of catalpol involves increased AMPK-mediated mitochondrial biogenesis. Acta Pharmacol Sin 41, 791–799 (2020). https://doi.org/10.1038/s41401-019-0345-2
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DOI: https://doi.org/10.1038/s41401-019-0345-2
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