title: Proteomic analysis reveals cellular pathways regulating carbohydrate metabolism that are modulated in primary human skeletal muscle culture due to treatment with bioactives from Artemisia dracunculus L.
abstract: Insulin resistance is a major pathophysiologic abnormality that characterizes metabolic syndrome and type 2 diabetes. A well characterized ethanolic extract of Artemisia dracunculus L., termed PMI 5011, has been shown to improve insulin action in vitro and in vivo, but the cellular mechanisms remain elusive. Using differential proteomics, we have studied mechanisms by which PMI 5011 enhances insulin action in primary human skeletal muscle culture obtained by biopsy from obese, insulin-resistant individuals. Using iTRAQ™ labeling and LC-MS/MS, we have identified over 200 differentially regulated proteins due to treatment with PMI 5011 and insulin stimulation. Bioinformatics analyses determined that several metabolic pathways related to glycolysis, glucose transport and cell signaling were highly represented and differentially regulated in the presence of PMI 5011 indicating that this extract affects several pathways modulating carbohydrate metabolism, including translocation of GLUT4 to the plasma membrane. These findings provide a molecular mechanism by which a botanical extract improves insulin stimulated glucose uptake, transport and metabolism at the cellular level resulting in enhanced whole body insulin sensitivity.
authors.affiliation: Protein Structural Biology, Pennington Biomedical Research Center, Louisiana State University System, 6400 Perkins Road, Baton Rouge, LA 70808, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Scherp
authors.forename: Nagireddy
authors.initials: N
authors.lastname: Putluri
authors.forename: Gary J
authors.initials: GJ
authors.lastname: LeBlanc
authors.forename: Zhong Q
authors.initials: ZQ
authors.lastname: Wang
authors.forename: Xian H
authors.initials: XH
authors.lastname: Zhang
authors.forename: Yongmei
authors.initials: Y
authors.lastname: Yu
authors.forename: David
authors.initials: D
authors.lastname: Ribnicky
authors.forename: William T
authors.initials: WT
authors.lastname: Cefalu
authors.forename: Indu
authors.initials: I
authors.lastname: Kheterpal
mesh_terms: D000818:Animals; D019306:Artemisia / Q000737:chemistry*; D050260:Carbohydrate Metabolism / Q000187:drug effects*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D006801:Humans; D007333:Insulin Resistance; D009124:Muscle Proteins / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D040901:Proteomics / Q000379:methods; D046509:Tissue Culture Techniques
chemical_list: D009124:Muscle Proteins; D010936:Plant Extracts