title: Ameliorative effects of polyunsaturated fatty acids against palmitic acid-induced insulin resistance in L6 skeletal muscle cells.
abstract: BACKGROUND
  Fatty acid-induced insulin resistance and impaired glucose uptake activity in muscle cells are fundamental events in the development of type 2 diabetes and hyperglycemia. There is an increasing demand for compounds including drugs and functional foods that can prevent myocellular insulin resistance.
  
  
  METHODS
  In this study, we established a high-throughput assay to screen for compounds that can improve myocellular insulin resistance, which was based on a previously reported non-radioisotope 2-deoxyglucose (2DG) uptake assay. Insulin-resistant muscle cells were prepared by treating rat L6 skeletal muscle cells with 750 μM palmitic acid for 14 h. Using the established assay, the impacts of several fatty acids on myocellular insulin resistance were determined.
  
  
  RESULTS
  In normal L6 cells, treatment with saturated palmitic or stearic acid alone decreased 2DG uptake, whereas unsaturated fatty acids did not. Moreover, co-treatment with oleic acid canceled the palmitic acid-induced decrease in 2DG uptake activity. Using the developed assay with palmitic acid-induced insulin-resistant L6 cells, we determined the effects of other unsaturated fatty acids. We found that arachidonic, eicosapentaenoic and docosahexaenoic acids improved palmitic acid-decreased 2DG uptake at lower concentrations than the other unsaturated fatty acids, including oleic acid, as 10 μM arachidonic acid showed similar effects to 750 μM oleic acid.
  
  
  CONCLUSIONS
  We have found that polyunsaturated fatty acids, in particular arachidonic and eicosapentaenoic acids prevent palmitic acid-induced myocellular insulin resistance.
authors.affiliation: Department of Agrobioscience, Graduate School of Agricultural Science, Kobe University, Kobe, Hyogo 657-8501, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Sawada
authors.forename: Kyuichi
authors.initials: K
authors.lastname: Kawabata
authors.forename: Takatoshi
authors.initials: T
authors.lastname: Yamashita
authors.forename: Kengo
authors.initials: K
authors.lastname: Kawasaki
authors.forename: Norio
authors.initials: N
authors.lastname: Yamamoto
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Ashida
mesh_terms: D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003847:Deoxyglucose / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D051275:Glucose Transporter Type 4 / Q000235:genetics / Q000378:metabolism; D057166:High-Throughput Screening Assays / Q000379:methods*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007333:Insulin Resistance; D018485:Muscle Fibers, Skeletal / Q000187:drug effects* / Q000378:metabolism; D019308:Palmitic Acid; D051381:Rats; D011972:Receptor, Insulin / Q000235:genetics / Q000378:metabolism
chemical_list: D005231:Fatty Acids, Unsaturated; D051275:Glucose Transporter Type 4; D007004:Hypoglycemic Agents; C495694:Slc2a4 protein, rat; D019308:Palmitic Acid; D003847:Deoxyglucose; D011972:Receptor, Insulin