title: Oleuropein activated AMPK and induced insulin sensitivity in C2C12 muscle cells.
abstract: OBJECTIVE
  Oleuropein has been recognized as an important medicinal compound because of its various biological properties, including anti-cancer, antidiabetic and anti-atherosclerotic activities. Here, we evaluate the antioxidant activity as well as the mechanism of the hypoglycemic effects of oleuropein in C2C12 cells and we establish the mechanism underlying these effects.
  
  
  METHODS
  To perform this study, C2C12 cells viability was analyzed via MTT assay and the antioxidant activity was investigated by ROS and TBARS assays. Also, the effect of oleuropein on AMPK and PI3 kinase signaling pathways was evaluated.
  
  
  RESULTS
  Treatment with oleuropein was able to protect cells against H2O2 induced stress in cells. On the other hand, the molecular bases of its actions have been scarcely understood. Oleuropein significantly enhanced glucose consumption and the phosphorylation of AMPK (AMP-activated protein kinase/ACC (acetyl-CoA carboxylase)) and MAPKs (mitogen-activated protein kinases), but not PI3 kinase (Phosphatidylinositol 3-kinase)/Akt. However, the co-treatment of oleuropein and insulin improved the insulin sensitivity via insulin-dependent (PI3 kinase/Akt) and insulin independent (AMPK/ACC) pathways. These results could be confirmed from the findings of GLUT4 translocation which was strongly enhanced in the case of oleuropein.
  
  
  CONCLUSIONS
  Our results provide important insights for the possible mechanism of action of oleuropein as a therapeutic agent in diabetic patients.
authors.affiliation: Environmental Bioprocesses Laboratory, Laboratoire Mixte International (LMI-COSYS-MED), Sfax Biotechnology Center, P.O. Box 1177, Sfax 3038, Tunisia.
authors.forename: Fatma
authors.initials: F
authors.lastname: Hadrich
authors.affiliation: INSERM UMR S938, Centre de Recherche Saint-Antoine, F-75012 Paris, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Garcia
authors.affiliation: Environmental Bioprocesses Laboratory, Laboratoire Mixte International (LMI-COSYS-MED), Sfax Biotechnology Center, P.O. Box 1177, Sfax 3038, Tunisia.
authors.forename: Amina
authors.initials: A
authors.lastname: Maalej
authors.affiliation: INSERM UMR S938, Centre de Recherche Saint-Antoine, F-75012 Paris, France.
authors.forename: Marthe
authors.initials: M
authors.lastname: Moldes
authors.affiliation: Alliance for Research on North Africa (ARENA), University of Tsukuba, Tsukuba, Ibaraki 305-8572, Japan; Faculty of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8572, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Isoda
authors.affiliation: INSERM UMR S938, Centre de Recherche Saint-Antoine, F-75012 Paris, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Feve
authors.affiliation: Environmental Bioprocesses Laboratory, Laboratoire Mixte International (LMI-COSYS-MED), Sfax Biotechnology Center, P.O. Box 1177, Sfax 3038, Tunisia.. Electronic address: sami.sayadi@cbs.rnrt.tn.
authors.forename: Sami
authors.initials: S
authors.lastname: Sayadi
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000378:metabolism; D004357:Drug Synergism; D004789:Enzyme Activation / Q000187:drug effects; D006861:Hydrogen Peroxide / Q000633:toxicity; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D057888:Iridoid Glucosides; D039823:Iridoids / Q000494:pharmacology*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D018482:Muscle, Skeletal / Q000166:cytology* / Q000201:enzymology / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D020011:Protective Agents / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D007004:Hypoglycemic Agents; D007328:Insulin; D057888:Iridoid Glucosides; D039823:Iridoids; D020011:Protective Agents; D017382:Reactive Oxygen Species; C480633:SLC2A4RG protein, human; D017392:Thiobarbituric Acid Reactive Substances; D014157:Transcription Factors; C002769:oleuropein; D006861:Hydrogen Peroxide; D058539:Phosphatidylinositol 3-Kinase; D020928:Mitogen-Activated Protein Kinases; D055372:AMP-Activated Protein Kinases
keywords: AMPK; Insulin sensitivity; MAPK; Oleuropein; Skeletal muscle cells