@article{d9d5b1c6bd8444aab6ca2f9356dd84fa,
title = "Lipoic acid protects against oxidative stress induced impairment in insulin stimulation of protein kinase B and glucose transport in 3T3-L1 adipocytes",
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-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-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.",
keywords = "GLUT4 translocation, Insulin resistance, Troglitazone, Vitamin C, Vitamin E",
author = "A. Rudich and A. Tirosh and R. Potashnik and M. Khamaisi and N. Bashan",
note = "Funding Information: Acknowledgements. This work was supported by grants from the Israeli Ministry of Health and from the Israeli Academy of Sciences (both to N. Bashan and A. Rudich) and by the American Physician Fellowship Edward H. Kass Fund Award (to A. Rudich).",
year = "1999",
doi = "10.1007/s001250051253",
language = "אנגלית",
volume = "42",
pages = "949--957",
journal = "Diabetologia",
issn = "0012-186X",
publisher = "Springer Verlag",
number = "8",
}