title: Bioactives of Artemisia dracunculus L. enhance insulin sensitivity by modulation of ceramide metabolism in rat skeletal muscle cells.
abstract: OBJECTIVE
  An increase in ectopic lipids in peripheral tissues has been implicated in attenuating insulin action. The botanical extract of Artemisia dracunculus L. (PMI 5011) improves insulin action, yet the precise mechanism is unknown. The aim of this study was to determine whether the mechanism by which the bioactive compounds in PMI 5011 improve insulin signaling is through regulation of ceramide metabolism.
  
  
  METHODS
  L6 Myotubes were separately preincubated with 250 μM palmitic acid with or without PMI 5011 or four bioactive compounds isolated from PMI 5011 and postulated to be responsible for the effect. The effects on insulin signaling, ceramide, and glucosylceramide profiles were determined.
  
  
  RESULTS
  Treatment of L6 myotubes with palmitic acid resulted in increased levels of total ceramides and glucosylceramides, and cell surface expression of gangliosides. Palmitic acid also inhibited insulin-stimulated phosphorylation of protein kinase B/Akt and reduced glycogen accumulation. Bioactives from PMI 5011 had no effect on ceramide formation but one active compound (DMC-2) and its synthetic analog significantly reduced glucosylceramide accumulation and increased insulin sensitivity via restoration of Akt phosphorylation.
  
  
  CONCLUSIONS
  The observations suggest that insulin sensitization by PMI 5011 is partly mediated through moderation of glycosphingolipid accumulation.
authors.affiliation: Diabetes and Nutrition Research Laboratory, Pennington Biomedical Research Center, LSU System, Baton Rouge, Louisiana, USA.
authors.forename: Diana N
authors.initials: DN
authors.lastname: Obanda
authors.affiliation: Department of Plant Biology and Pathology, Rutgers University, The State University of New Jersey, The Biotech Center, New Brunswick, New Jersey, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Ribnicky
authors.affiliation: Department of Plant Biology and Pathology, Rutgers University, The State University of New Jersey, The Biotech Center, New Brunswick, New Jersey, USA.
authors.forename: Ilya
authors.initials: I
authors.lastname: Raskin
authors.affiliation: Diabetes and Nutrition Research Laboratory, Pennington Biomedical Research Center, LSU System, Baton Rouge, Louisiana, USA. Electronic address: Cefaluwt@pbrc.edu.
authors.forename: William T
authors.initials: WT
authors.lastname: Cefalu
mesh_terms: D000818:Animals; D019306:Artemisia / Q000737:chemistry*; D002518:Ceramides / Q000096:biosynthesis / Q000378:metabolism; D047188:Chalcones / Q000494:pharmacology*; D005963:Glucosylceramides / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000378:metabolism; D018482:Muscle, Skeletal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D019308:Palmitic Acid / Q000494:pharmacology; D010766:Phosphorylation; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats
chemical_list: C514624:2',4'-dihydroxy-4-methoxydihydrochalcone; D002518:Ceramides; D047188:Chalcones; D005963:Glucosylceramides; D007328:Insulin; C541449:PMI-5011; D010936:Plant Extracts; D019308:Palmitic Acid; D051057:Proto-Oncogene Proteins c-akt
keywords: Akt phosphorylation; Botanicals; Glycosphingolipids; Insulin resistance