title: The lipid peroxidation end-product and oxidant 4-hydroxynonenal induces insulin resistance in rat slow-twitch skeletal muscle.
abstract: BACKGROUND
  The lipid peroxidation end-product and oxidant 4-hydroxynonenal (4-HNE) impairs cell function. However, the impact of 4-HNE on the glucose transport system in mammalian slow-twitch skeletal muscle is not known.
  
  
  OBJECTIVE
  We assessed the effects of 4-HNE on insulin signalling and glucose transport activity in slow-twitch muscle by incubating soleus strips from lean Zucker rats with 4-HNE (50 µM) in the absence or presence of insulin (5 mU/ml) for up to 6 hr.
  
  
  RESULTS
  Insulin-stimulated glucose transport activity was significantly (p<0.05) decreased by 4-HNE at 2 hr. AS160 Thr(642) phosphorylation was decreased at 2 hr, whereas Akt Ser473 phosphorylation and IRS-1 protein expression were not substantially changed until 4 hr. IRS-2 protein expression was slightly decreased only at 6 hr.
  
  
  CONCLUSIONS
  The lipid peroxidation end-product and oxidant 4-HNE induces insulin resistance of glucose transport activity in rat slow-twitch skeletal muscle, initially associated with impaired phosphorylation of AS160.
authors.affiliation: Muscle Metabolism Laboratory, Department of Physiology, University of Arizona College of Medicine , Tucson, AZ , USA.
authors.forename: Mujalin
authors.initials: M
authors.lastname: Prasannarong
authors.forename: Fernando R
authors.initials: FR
authors.lastname: Santos
authors.forename: Payam
authors.initials: P
authors.lastname: Hooshmand
authors.forename: Paria
authors.initials: P
authors.lastname: Hooshmand
authors.forename: Franchesca J
authors.initials: FJ
authors.lastname: Giovannini
authors.forename: Erik J
authors.initials: EJ
authors.lastname: Henriksen
mesh_terms: D000447:Aldehydes / Q000494:pharmacology*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D005260:Female; D020690:GTPase-Activating Proteins / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D066298:In Vitro Techniques; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism; D007333:Insulin Resistance; D015227:Lipid Peroxidation / Q000187:drug effects*; D018482:Muscle, Skeletal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D016877:Oxidants / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D011924:Rats, Zucker; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000447:Aldehydes; D020690:GTPase-Activating Proteins; D055504:Insulin Receptor Substrate Proteins; D016877:Oxidants; C533101:TBC1D4 protein, rat; D051057:Proto-Oncogene Proteins c-akt; D005947:Glucose; C027576:4-hydroxy-2-nonenal