title: Carnosic acid as a component of rosemary extract stimulates skeletal muscle cell glucose uptake via AMPK activation.
abstract: Compounds that increase the activity of the energy sensor AMP-activated kinase (AMPK) have the potential to regulate blood glucose levels. Although rosemary extract (RE) has been reported to activate AMPK and reduce blood glucose levels in vivo, the chemical components responsible for these effects are not known. In the present study, we measured the levels of the polyphenol carnosic acid (CA) in RE and examined the effects and the mechanism of action of CA on glucose transport system in muscle cells. High performance liquid chromatography (HPLC) was used to measure the levels of CA in RE. Parental and GLUT4myc or GLUT1myc overexpressing L6 rat myotubes were used. Glucose uptake was assessed using [3H]-2-deoxy-d-glucose. Total and phosphorylated levels of Akt and AMPK were measured by immunoblotting. Plasma membrane GLUT4myc and GLUT1myc levels were examined using a GLUT translocation assay. Statistics included analysis of variance (ANOVA) followed by Tukey's post-hoc test. At concentrations found in rosemary extract, CA stimulated glucose uptake in L6 myotubes. At 2.0 μmol/L CA a response (226 ± 9.62% of control, P=.001), similar to maximum insulin (201 ± 7.86% of control, P=.001) and metformin (213 ± 10.74% of control, P=.001) was seen. Akt phosphorylation was not affected by CA while AMPK and ACC phosphorylation was increased and the CA-stimulated glucose uptake was significantly reduced by the AMPK inhibitor compound C. Plasma membrane GLUT4 or GLUT1 glucose transporter levels were not affected by CA. Our study shows increased muscle cell glucose uptake and AMPK activation by low CA concentrations, found in rosemary extract, indicating that CA may be responsible for the antihyperglycemic properties of rosemary extract seen in vivo.
authors.affiliation: Department of Health Sciences, Brock University, St. Catharines, ON, Canada.
authors.forename: Madina
authors.initials: M
authors.lastname: Naimi
authors.affiliation: Department of Health Sciences, Brock University, St. Catharines, ON, Canada.
authors.forename: Filip
authors.initials: F
authors.lastname: Vlavcheski
authors.affiliation: Department of Chemistry, Brock University, St. Catharines, ON, Canada.
authors.forename: Brennan
authors.initials: B
authors.lastname: Murphy
authors.affiliation: Department of Chemistry, Brock University, St. Catharines, ON, Canada.
authors.forename: Tomas
authors.initials: T
authors.lastname: Hudlicky
authors.affiliation: Department of Health Sciences, Brock University, St. Catharines, ON, Canada.|Centre for Bone and Muscle Health, Brock University, St. Catharines, ON, Canada.
authors.forename: Evangelia
authors.initials: E
authors.lastname: Tsiani
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D045784:Abietanes / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000378:metabolism*; D032342:Muscle Cells / Q000187:drug effects / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology; D051381:Rats; D027542:Rosmarinus
chemical_list: D045784:Abietanes; D010936:Plant Extracts; D055372:AMP-Activated Protein Kinases; D005947:Glucose; C018381:salvin
keywords: 
  AMPK
  ; carnosic acid; glucose uptake; muscle