BMS309403 Stimulates Glucose Uptake in Myotubes through Activation of AMP-Activated Protein Kinase

BMS309403 is a biphenyl azole inhibitor against fatty acid binding protein 4 (FABP4) and regarded as a lead compound for effective treatment of obesity related cardio-metabolic diseases. Here we discovered an off-target activity of BMS309403 in that it stimulates glucose uptake in C2C12 myotubes in...

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Autores principales: Lin, Wanhua, Huang, Xiaoli, Zhang, Lina, Chen, Dongmei, Wang, Dongye, Peng, Qilong, Xu, Lei, Li, Jingya, Liu, Xiujie, Li, Kuai, Ding, Ke, Jin, Shouguang, Li, Jia, Wu, Donghai
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Research Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3432117/
https://www.ncbi.nlm.nih.gov/pubmed/22952994
http://dx.doi.org/10.1371/journal.pone.0044570
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author Lin, Wanhua
Huang, Xiaoli
Zhang, Lina
Chen, Dongmei
Wang, Dongye
Peng, Qilong
Xu, Lei
Li, Jingya
Liu, Xiujie
Li, Kuai
Ding, Ke
Jin, Shouguang
Li, Jia
Wu, Donghai
author_facet Lin, Wanhua
Huang, Xiaoli
Zhang, Lina
Chen, Dongmei
Wang, Dongye
Peng, Qilong
Xu, Lei
Li, Jingya
Liu, Xiujie
Li, Kuai
Ding, Ke
Jin, Shouguang
Li, Jia
Wu, Donghai
author_sort Lin, Wanhua
collection PubMed
description BMS309403 is a biphenyl azole inhibitor against fatty acid binding protein 4 (FABP4) and regarded as a lead compound for effective treatment of obesity related cardio-metabolic diseases. Here we discovered an off-target activity of BMS309403 in that it stimulates glucose uptake in C2C12 myotubes in a temporal and dose dependent manner via activation of AMP-activated protein kinase (AMPK) signaling pathway but independent of FABPs. Further analysis indicated that BMS309403 activates AMPK through increasing the ratio of intracellular AMP:ATP while decreasing mitochondrial membrane potential. These findings provide mechanistic insights on the action of BMS309403.
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spelling pubmed-34321172012-09-05 BMS309403 Stimulates Glucose Uptake in Myotubes through Activation of AMP-Activated Protein Kinase Lin, Wanhua Huang, Xiaoli Zhang, Lina Chen, Dongmei Wang, Dongye Peng, Qilong Xu, Lei Li, Jingya Liu, Xiujie Li, Kuai Ding, Ke Jin, Shouguang Li, Jia Wu, Donghai PLoS One Research Article BMS309403 is a biphenyl azole inhibitor against fatty acid binding protein 4 (FABP4) and regarded as a lead compound for effective treatment of obesity related cardio-metabolic diseases. Here we discovered an off-target activity of BMS309403 in that it stimulates glucose uptake in C2C12 myotubes in a temporal and dose dependent manner via activation of AMP-activated protein kinase (AMPK) signaling pathway but independent of FABPs. Further analysis indicated that BMS309403 activates AMPK through increasing the ratio of intracellular AMP:ATP while decreasing mitochondrial membrane potential. These findings provide mechanistic insights on the action of BMS309403. Public Library of Science 2012-08-31 /pmc/articles/PMC3432117/ /pubmed/22952994 http://dx.doi.org/10.1371/journal.pone.0044570 Text en © 2012 Lin et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Lin, Wanhua
Huang, Xiaoli
Zhang, Lina
Chen, Dongmei
Wang, Dongye
Peng, Qilong
Xu, Lei
Li, Jingya
Liu, Xiujie
Li, Kuai
Ding, Ke
Jin, Shouguang
Li, Jia
Wu, Donghai
BMS309403 Stimulates Glucose Uptake in Myotubes through Activation of AMP-Activated Protein Kinase
title BMS309403 Stimulates Glucose Uptake in Myotubes through Activation of AMP-Activated Protein Kinase
title_full BMS309403 Stimulates Glucose Uptake in Myotubes through Activation of AMP-Activated Protein Kinase
title_fullStr BMS309403 Stimulates Glucose Uptake in Myotubes through Activation of AMP-Activated Protein Kinase
title_full_unstemmed BMS309403 Stimulates Glucose Uptake in Myotubes through Activation of AMP-Activated Protein Kinase
title_short BMS309403 Stimulates Glucose Uptake in Myotubes through Activation of AMP-Activated Protein Kinase
title_sort bms309403 stimulates glucose uptake in myotubes through activation of amp-activated protein kinase
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3432117/
https://www.ncbi.nlm.nih.gov/pubmed/22952994
http://dx.doi.org/10.1371/journal.pone.0044570
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