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Antidiabetic effects of betulinic acid mediated by the activation of the AMP-activated protein kinase pathway.
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- Author(s): Song, Tae-Jun1 (AUTHOR); Park, Choon-Ho2 (AUTHOR); In, Kyu-Ree3 (AUTHOR); Kim, Jong-Bae1 (AUTHOR); Kim, Joo Hee4 (AUTHOR); Kim, Miran5 (AUTHOR); Chang, Hye Jin5 (AUTHOR)
- Source:
PLoS ONE. 4/5/2021, Vol. 16 Issue 4, p1-16. 16p.- Subject Terms:
- Source:
- Additional Information
- Abstract: Betulinic acid (BA) is a naturally arising pentacyclic triterpenoid that has anti-malarial, anti-retroviral, anti-inflammatory, and anti-cancer biological effects. More recently, it has been reported to possess anti-obesity activity mediated by the activation of AMP-activated protein kinase (AMPK). We further investigated antidiabetic activity of BA in mouse tissues at the cellular and systemic levels. We found that BA stimulated AMPK in a similar fashion to the known AMPK activators, such as 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside and metformin. Notably, the level of glucose uptake by BA was not altered by wortmannin, suggesting that this activation did not depend on phosphoinositide 3-kinase. Furthermore, BA diminished blood glucose levels in alloxane-treated ICR mice and in untreated mice during the glucose tolerance test. BA also stimulated mRNA expression of glucose transporter 4, which could partly explain increased glucose uptake. BA also increased AS160 phosphorylation by insulin-independent mechanisms in the extensor digitorum longus muscle. These results indicate that BA may serve as a promising therapeutic agent for diabetes by activating AMPK, like metformin. Notably, BA also enhanced mouse endurance capacity, indicating that it also affects metabolic regulation in addition to its antidiabetic activity. [ABSTRACT FROM AUTHOR]
- Abstract: Copyright of PLoS ONE is the property of Public Library of Science and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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