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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Detalles Bibliográficos
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
Descripción
Sumario: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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