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

Aims/hypothesis. Oxidative stress has been shown to impair insulin-stimulat ed glucose transporter 4 translocation in 3T3-L1 adipocytes. This study exp lores the potential of the antioxidant lipoic acid to protect the cells aga inst the induction of insulin resistance when given before exposure to oxid ative stress. Methods. 3T3-LI 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-stimula ted glucose transport activity associated with a decrease in reduced glutat hione 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, associat ed with an increase in reduced glutathione content. Oxidation impaired the 4.89 +/- 0.36-fold insulin-stimulated increase in glucose transporter 4 con tent in plasma membrane lawns of control cells. Lipoic acid pretreatment wa s, 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 b y lipoic acid pretreatment, insulin-stimulated protein kinase B/Akt serine 473 phosphorylation and activity were considerably impaired by oxidation bu t protected by lipoic acid pretreatment. A protective effect was not observ ed with either troglitazone, its isolated vitamin E moiety, or with vitamin C. Conclusion/interpretation. This study shows the ab iii ty 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 re dox state.