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

• Published in: PloS one Vol. 7; no. 8; p. e44570
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 31.08.2012; Public Library of Science (PLoS)
• Subjects: Activation; Adenosine Monophosphate - metabolism; Adenosine Triphosphate - metabolism; Adipocytes; AMP; AMP-activated protein kinase; AMP-Activated Protein Kinases - metabolism; Analysis; Animals; Atherosclerosis; Biology; Biphenyl; Biphenyl Compounds - pharmacology; Blotting, Western; Cell Line; Cytosol - metabolism; Development and progression; Diabetes; Drug dosages; Enzyme Activation - drug effects; Fatty Acid Binding Protein 3; Fatty acid-binding protein; Fatty Acid-Binding Proteins - metabolism; Fatty acids; Gene Knockdown Techniques; Genetic aspects; Glucose; Glucose - metabolism; Kinases; Laboratories; Lipids; Medical treatment; Medicine; Membrane potential; Membrane Potential, Mitochondrial - drug effects; Metabolic disorders; Mice; Mitochondria; Muscle Fibers, Skeletal - drug effects; Muscle Fibers, Skeletal - enzymology; Musculoskeletal system; Myotubes; Obesity; p38 Mitogen-Activated Protein Kinases - metabolism; Phosphorylation; Phosphorylation - drug effects; Physiological aspects; Protein kinases; Proteins; Pyrazoles - pharmacology; Signal transduction; Signal Transduction - drug effects; Signaling; Time Factors; China
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0044570

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.