title: Endoplasmic reticulum stress does not mediate palmitate-induced insulin resistance in mouse and human muscle cells.
abstract: OBJECTIVE
  Recent experiments in liver and adipocyte cell lines indicate that palmitate can induce endoplasmic reticulum (ER) stress. Since it has been shown that ER stress can interfere with insulin signalling, our hypothesis was that the deleterious action of palmitate on the insulin signalling pathway in muscle cells could also involve ER stress.
  
  
  METHODS
  We used C2C12 and human myotubes that were treated either with palmitate or tunicamycin. Total lysates and RNA were prepared for western blotting or quantitative RT-PCR respectively. Glycogen synthesis was assessed by [¹⁴C]glucose incorporation.
  
  
  RESULTS
  Incubation of myotubes with palmitate or tunicamycin inhibited insulin-stimulated protein kinase B (PKB)/ v-akt murine thymoma viral oncogene homologue 1 (Akt). In parallel, an increase in ER stress markers was observed. Pre-incubation with chemical chaperones that reduce ER stress only prevented tunicamycin but not palmitate-induced insulin resistance. We hypothesised that ER stress activation levels induced by palmitate may not be high enough to induce insulin resistance, in contrast with tunicamycin-induced ER stress. Indeed, tunicamycin induced a robust activation of the inositol-requiring enzyme 1 (IRE-1)/c-JUN NH₂-terminal kinase (JNK) pathway, leading to serine phosphorylation of insulin receptor substrate 1 (IRS-1) and a decrease in IRS-1 tyrosine phosphorylation. In contrast, palmitate only induced a very weak activation of the IRE1/JNK pathway, with no IRS1 serine phosphorylation.
  
  
  CONCLUSIONS
  These data show that insulin resistance induced by palmitate is not related to ER stress in muscle cells.
authors: Inserm, UMR-S 872, Centre de Recherche des Cordeliers, Paris 75006, France.
authors: R
authors: R
authors: Hage Hassan
authors: I
authors: I
authors: Hainault
authors: J-T
authors: JT
authors: Vilquin
authors: C
authors: C
authors: Samama
authors: F
authors: F
authors: Lasnier
authors: P
authors: P
authors: Ferré
authors: F
authors: F
authors: Foufelle
authors: E
authors: E
authors: Hajduch
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D004722:Endoribonucleases / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D006031:Glycosylation / Q000187:drug effects; D006801:Humans; D007333:Insulin Resistance; D051379:Mice; D032342:Muscle Cells / Q000187:drug effects / Q000378:metabolism*; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000378:metabolism; D032446:Myoblasts / Q000187:drug effects / Q000378:metabolism; D019308:Palmitic Acid / Q000009:adverse effects*; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014415:Tunicamycin / Q000494:pharmacology
chemical_list: D015415:Biomarkers; D014415:Tunicamycin; D019308:Palmitic Acid; D006003:Glycogen; C528229:ERN1 protein, human; C510185:Ern1 protein, mouse; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D004722:Endoribonucleases