Insulin resistance is a key factor of metabolic syndrome and can lead to pre-diabetes, diabetes and cardiovascular disease. PMI-5011, an ethanolic extract from Russian Tarragon (Artemisia dracunculus L.) has been shown to increase insulin signaling in skeletal muscle of humans and rodents, resulting in improved insulin sensitivity. Despite extensive research, the exact mode of action of PMI-5011 has not been established. Here we present results from proteomic analyses of human skeletal muscle cell cultures (HSMC) derived from obese, insulin-resistant individuals. Using isobaric tagging for relative and absolute quantification (iTRAQ), we analyzed four treatments (baseline control; control with insulin stimulation; PMI-5011 treated; PMI-5011 treated with insulin stimulation) simultaneously using strong cation exchange chromatography and reverse-phase liquid chromatography-tandem mass spectrometry. Our results show that HSMCs retained the intrinsic properties of skeletal muscle cells; thus, HSMC from obese insulin resistant individuals showed a blunted response to insulin stimulation in vitro. Treatment of cells with PMI-5011 in the presence of insulin resulted in an increase of proteins involved in glycolysis/gluconeogenesis pathway, actin cytoskeleton signaling and interleukin signaling. Furthermore, we detected reduction in levels of proteins from inflammatory networks that involve tumor necrosis factor receptor that reduces activity of nuclear factor kappa B (NFκB). These results show that PMI-5011 increases protein abundance in key metabolic pathways of glucose metabolism and modulates proteins that lead to reduced inflammatory cytokine signaling, likely resulting in observed increase in insulin sensitivity.
