BMS309403 stimulates glucose uptake in myotubes through activation of AMP-activated protein kinase

  • PLoS One. 2012;7(8):e44570. doi: 10.1371/journal.pone.0044570.
Wanhua Lin  1 ,  Xiaoli Huang ,  Lina Zhang ,  Dongmei Chen ,  Dongye Wang ,  Qilong Peng ,  Lei Xu ,  Jingya Li ,  Xiujie Liu ,  Kuai Li ,  Ke Ding ,  Shouguang Jin ,  Jia Li ,  Donghai Wu
Affiliations
  • 1. The Key Laboratory of Regenerative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
PMID: 22952994 DOI: 10.1371/journal.pone.0044570
Abstract

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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