Lipoic acid protects against oxidative stress induced impairment in insulin stimulation of protein kinase B and glucose transport in 3T3-L1 adipocytes

Diabetologia. 1999 Aug;42(8):949-57. doi: 10.1007/s001250051253.

Abstract

Aims/hypothesis: 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.

Conclusion/interpretation: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Adipocytes / cytology
  • Adipocytes / drug effects
  • Adipocytes / metabolism*
  • Animals
  • Ascorbic Acid / pharmacology
  • Biological Transport / drug effects
  • Biological Transport / physiology
  • Chromans / pharmacology
  • Glucose / metabolism*
  • Glucose Oxidase / pharmacology
  • Glucose Transporter Type 4
  • Glutathione / metabolism
  • Hydrogen Peroxide / pharmacology
  • Hypoglycemic Agents / pharmacology
  • Insulin / pharmacology*
  • Mice
  • Monosaccharide Transport Proteins / metabolism
  • Muscle Proteins*
  • Oxidative Stress / drug effects
  • Oxidative Stress / physiology*
  • Protein-Serine-Threonine Kinases*
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins c-akt
  • Thiazoles / pharmacology
  • Thiazolidinediones*
  • Thioctic Acid / pharmacology*
  • Troglitazone
  • Vitamin E / pharmacology

Substances

  • Chromans
  • Glucose Transporter Type 4
  • Hypoglycemic Agents
  • Insulin
  • Monosaccharide Transport Proteins
  • Muscle Proteins
  • Proto-Oncogene Proteins
  • Slc2a4 protein, mouse
  • Thiazoles
  • Thiazolidinediones
  • Vitamin E
  • Thioctic Acid
  • Hydrogen Peroxide
  • Glucose Oxidase
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • Glutathione
  • Troglitazone
  • Glucose
  • Ascorbic Acid