title: Lipoic acid protects against oxidative stress induced impairment in insulin stimulation of protein kinase B and glucose transport in 3T3-L1 adipocytes.
abstract: OBJECTIVE
  Oxidative stress has been shown to impair insulin-stimulated glucose transporter 4 translocation in 3T3-L1 adipocytes. This study explores the potential of the antioxidant lipoic acid to protect the cells against the induction of insulin resistance when given before exposure to oxidative stress.
  
  
  METHODS
  3T3-L1 were exposed for 16 h to lipoic acid after which cells were exposed for 2 h to continuous production of H2O2 by adding glucose oxidase to the culture medium.
  
  
  RESULTS
  These conditions resulted in a 50-70% reduction in insulin-stimulated glucose transport activity associated with a decrease in reduced glutathione content from 37.4 +/- 3.1 to 26.4 +/- 4.9 nmol/mg protein, (p < 0.005). Lipoic acid pretreatment increased insulin-stimulated glucose transport following oxidative stress, reaching 84.8 +/- 4.4% of the control, associated with an increase in reduced glutathione content. Oxidation impaired the 4.89 +/- 0.36-fold insulin-stimulated increase in glucose transporter 4 content in plasma membrane lawns of control cells. Lipoic acid pretreatment was, however, associated with preserved insulin-induced glucose transporter 4 translocation in cells exposed to oxidation, yielding 80% of its content in controls. Although tyrosine phosphorylation patterns were not affected by lipoic acid pretreatment, insulin-stimulated protein kinase B/Akt serine 473 phosphorylation and activity were considerably impaired by oxidation but protected by lipoic acid pretreatment. A protective effect was not observed with either troglitazone, its isolated vitamin E moiety, or with vitamin C.
  
  
  CONCLUSIONS
  This study shows the ability of lipoic acid to provide partial protection against the impaired insulin-stimulated glucose transporter 4 translocation and protein kinase B/Akt activation induced by oxidative stress, potentially by its capacity to maintain intracellular redox state.
authors.affiliation: S. Daniel Abraham International Centre for Health and Nutrition, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
authors.forename: A
authors.initials: A
authors.lastname: Rudich
authors.forename: A
authors.initials: A
authors.lastname: Tirosh
authors.forename: R
authors.initials: R
authors.lastname: Potashnik
authors.forename: M
authors.initials: M
authors.lastname: Khamaisi
authors.forename: N
authors.initials: N
authors.lastname: Bashan
mesh_terms: D016475:3T3 Cells; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D002839:Chromans / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism*; D005949:Glucose Oxidase / Q000494:pharmacology; D051275:Glucose Transporter Type 4; D005978:Glutathione / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology*; D051379:Mice; D009004:Monosaccharide Transport Proteins / Q000378:metabolism; D009124:Muscle Proteins; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D013844:Thiazoles / Q000494:pharmacology; D045162:Thiazolidinediones; D008063:Thioctic Acid / Q000494:pharmacology*; D000077288:Troglitazone; D014810:Vitamin E / Q000494:pharmacology
chemical_list: D002839:Chromans; D051275:Glucose Transporter Type 4; D007004:Hypoglycemic Agents; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D011518:Proto-Oncogene Proteins; C495693:Slc2a4 protein, mouse; D013844:Thiazoles; D045162:Thiazolidinediones; D014810:Vitamin E; D008063:Thioctic Acid; D006861:Hydrogen Peroxide; D005949:Glucose Oxidase; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D005978:Glutathione; D000077288:Troglitazone; D005947:Glucose; D001205:Ascorbic Acid