title: Artemisia dracunculus L. extract ameliorates insulin sensitivity by attenuating inflammatory signalling in human skeletal muscle culture.
abstract: OBJECTIVE
  Bioactives of Artemisia dracunculus L. (termed PMI 5011) have been shown to improve insulin action by increasing insulin signalling in skeletal muscle. However, it was not known if PMI 5011's effects are retained during an inflammatory condition. We examined the attenuation of insulin action and whether PMI 5011 enhances insulin signalling in the inflammatory environment with elevated cytokines.
  
  
  METHODS
  Muscle cell cultures derived from lean, overweight and diabetic-obese subjects were used. Expression of pro-inflammatory genes and inflammatory response of human myotubes were evaluated by real-time polymerase chain reaction (RT-PCR). Insulin signalling and activation of inflammatory pathways in human myotubes were evaluated by multiplex protein assays.
  
  
  RESULTS
  We found increased gene expression of monocyte chemoattractant protein 1 (MCP1) and TNFα (tumour necrosis factor alpha), and basal activity of the NFkB (nuclear factor kappa-light-chain-enhancer of activated B cells) pathway in myotubes derived from diabetic-obese subjects as compared with myotubes derived from normal-lean subjects. In line with this, basal Akt phosphorylation (Ser473) was significantly higher, while insulin-stimulated phosphorylation of Akt (Ser473) was lower in myotubes from normal-overweight and diabetic-obese subjects compared with normal-lean subjects. PMI 5011 treatment reduced basal phosphorylation of Akt and enhanced insulin-stimulated phosphorylation of Akt in the presence of cytokines in human myotubes. PMI 5011 treatment led to an inhibition of cytokine-induced activation of inflammatory signalling pathways such as Erk1/2 and IkBα (nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha)-NFkB and moreover, NFkB target gene expression, possibly by preventing further propagation of the inflammatory response within muscle tissue.
  
  
  CONCLUSIONS
  PMI 5011 improved insulin sensitivity in diabetic-obese myotubes to the level of normal-lean myotubes despite the presence of pro-inflammatory cytokines.
authors: Gene Nutrient Interactions Laboratory, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LA, USA.
authors: B
authors: B
authors: Vandanmagsar
authors: K R
authors: KR
authors: Haynie
authors: S E
authors: SE
authors: Wicks
authors: E M
authors: EM
authors: Bermudez
authors: T M
authors: TM
authors: Mendoza
authors: D
authors: D
authors: Ribnicky
authors: W T
authors: WT
authors: Cefalu
authors: R L
authors: RL
authors: Mynatt
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D019440:Anti-Obesity Agents / Q000494:pharmacology; D019306:Artemisia / Q000737:chemistry*; D015992:Body Mass Index; D002478:Cells, Cultured; D016207:Cytokines / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D048909:Diabetes Complications / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007333:Insulin Resistance; D018485:Muscle Fibers, Skeletal / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D009765:Obesity / Q000150:complications / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D050177:Overweight / Q000150:complications / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D010936:Plant Extracts / Q000494:pharmacology*; D018515:Plant Leaves / Q000737:chemistry; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D019440:Anti-Obesity Agents; D016207:Cytokines; D007004:Hypoglycemic Agents; C541449:PMI-5011; D010936:Plant Extracts; C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt
keywords: Akt; Artemisia dracunculus L; Erk1/2; IL6; IRS1; IkBα; NFkB; PMI 5011; TNF; chemokines; cytokine signaling; cytokines; insulin resistance; insulin signaling; skeletal muscle inflammation