Lipoic Acid, a Metabolic Antioxidant Stimulates the Insulin Signaling Pathway in Adipocytes and Counteracts Oxidative Stress and Age Related Mitochondrial and Cognitive Dysfunction

  • Lester Packer
Conference paper
Part of the NATO Science Series book series (NAII, volume 129)


Healthy aging and disease prevention by antioxidant nutrition is increasingly a subject of academic and public health interest and research. Antioxidants play an important role in maintaining physiological redox status of cellular constituents against free radicals. Antioxidants may change their redox state, be targeted for destruction, regulate oxidative processes involved in signal transduction, affect gene expression and pathways of cell proliferation, as well as differentiation and death. This chapter will provide an overview of the antioxidant defense system with special relevance to the brain and aging.


Insulin Receptor Lipoic Acid Insulin Signaling Pathway Redox Regulation Thioctic Acid 
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  1. 1.
    Coran, M.H., Watanabe, H., Wolffram, S., Ader, P., Rimbach, G., Packer, L., Maguire, J.J., Schultz, P.G., and Gohil, K. (2001), The in vivo Neuromodulatory Effect of the Herbal Medicine Ginkgo Biloba, Proc. Natl. Acad. Sci. 98, 6577–6580.CrossRefGoogle Scholar
  2. 2.
    Fuchs, J., Packer, L., and Zimmer, G (1997) Lipoic Acid in Health and Disease, Marcel Dekker Inc., New York.Google Scholar
  3. 3.
    Lipoic acid in health and disease, (Fuchs, J., Packer, L. and Zimmer, G., eds.), Marcel Dekker, New York, Vol. 6, 1–496Google Scholar
  4. 4.
    Han, D., Handelman, G., Marcocci, L., Sen, C. K., Roy, S., Kobuchi, H., Tritschler, H. J., Flohé, L. and Packer, L (1997), Lipoic acid increases de novo synthesis of cellular glutathione by improving cystine utilization, BioFactors, 6, 321–338.CrossRefGoogle Scholar
  5. 5.
    Haramaki, N., Han, D., Handelman, G. J., Tritschler, H. J. and Packer, L (1997), Cytosolic and mitochondrial systems for NADH-and NADPH-dependent reduction of lipoic acid, Free Radic Biol Med, 22, 535–542.CrossRefGoogle Scholar
  6. 6.
    Haramaki, N., Packer, L., Assadnazari, H. and Zimmer, G (1993)., Cardiac recovery during post-ischemic reperfusion is improved by combination of vitamin E with dihydrolipoic acid, Biochem Biophys Res Commun, 196, 1101–7.CrossRefGoogle Scholar
  7. 7.
    Hendricksen, E (2000), Oxidative stress and antioxidant treatment: effects on muscle glucose transport in animal models of type 1 & type 2 diabetes in Lester Packer, Peter Rosen, Hans J Tritscler, George L King, and Angelo Azzi (Eds.), Antioxidants in diabetes management Marcel Dekker Inc., New York, NY, 303-317.Google Scholar
  8. 8.
    Liu, J, Atamna, H, and Ames, B.N (2001)., Delaying Brain Mitochondrial Decay and Aging with Mitochondrial Antioxidants and Metabolites, In: Increasing Healthy Life Span: Conventional Measures and Slowing the Innate Aging Process, (Ed: Harman, D.), Ann. N. Y. Acad. Sciences, in press.Google Scholar
  9. 9.
    Moini H, Tirosh O, Park YC, Cho KJ, Packer L (2002).,R-alpha-lipoic acid action on cell redox status, the insulin receptor, and glucose uptake in 3T3-L1 adipocytes. Arch Biochem Biophys, 397, 384–91.CrossRefGoogle Scholar
  10. 10.
    Packer, L., Rosen, P., Tritschler, H.J. King, G. and Azzi, A., Eds (2000), Antioxidants in Diabetes Management,, In: Oxidative Stress and Disease Series (Packer,L and Cadenas, E, volume editors) Marcel Dekker Inc New York 1-349.Google Scholar
  11. 11.
    Packer, L. and Tritschler, H. J.(1996), Alpha-lipoic acid — the metabolic antioxidant, Free Radie Biol Med, 20, 625–626.CrossRefGoogle Scholar
  12. 12.
    Packer, L., Witt, E. H. and Tritschler, H. J (1995), Alpha-Lipoic acid as a biological antioxidant, Free Radie Biol Med, 19, 227–250.CrossRefGoogle Scholar
  13. 13.
    Packer, L. (1994), Antioxidant properties of lipoic acid and its therapeutic effects in prevention of diabetes complications and cataracts, In: The Neurobiology of NO· and ·OH (C. Chiueh, D. Gilbert and C. Colton, eds.), Annals of the New York Academy of Sciences, New York, 738, 257–264.CrossRefGoogle Scholar
  14. 14.
    Packer, L.(1993), The possible role of vitamin E and thioctic acid in diabetic neuropathy, In: The Role of Anti-Oxidants in Diabetes Mellitus, 182-192.Google Scholar
  15. 15.
    Packer L, Tritschler HJ, Wessel K.(1997)., Neuroprotection by the metabolic antioxidant lipoic acid. Free Radie Biol Med, 22, 359–78.CrossRefGoogle Scholar
  16. 16.
    Packer, L. and Yodoi, L (1999), eds., Redox Regulation of Cell Signalling and Its clinical Application, Marcel Dekker, Inc., New York, NY, 1-328.Google Scholar
  17. 17.
    Packer, L., E. H. Witt, et al. (1995). “α-Lipoic acid as a biological antioxidant.” Free Radical Biology & Medicine 19, 227–250.CrossRefGoogle Scholar
  18. 18.
    Packer, L., H. Tritschler, et al. (1996). “Neuroprotection by the Metabolic antioxidant a-lipoic acid.” Free Radical Biology & Medicine 22, 359–378.CrossRefGoogle Scholar
  19. 19.
    Packer, L.(1996)., Prevention of Free Radical Damage in the Brain: Protection by a-lipoic acid, In: Packer, L., Hiramatsu, M, Yoshikawa,T., Free Radicals in Brain Physiology and Disorders, Academic Press 19-34.Google Scholar
  20. 20.
    Pick, U., Haramaki, N., Constantinescu, A., Handelman, G. J., Tritschler, H. J. and Packer, L.(1995)., Glutathione reductase and lipoamide dehydrogenase have opposite stereospecificities for alpha-lipoic acid enantiomers, Biochem Biophys Res Commun, 206, 724–730.CrossRefGoogle Scholar
  21. 21.
    Podda, M., Tritschler, H. J., Ulrich, H. and Packer, L.(1994), Alpha-lipoic acid supplementation prevents symptoms of vitamin E deficiency, Biochem Biophys Res Commun, 204, 98–104.CrossRefGoogle Scholar
  22. 22.
    Sen, C. K. and Packer, L.(1999), Redox regulation of cellular responses by lipoic acid, In: Redox Regulation in Cell Signaling and Clinical Applications. (L. Packer and J. Yodoi, eds.), Marcel Dekker, Inc., New York, NY, 299-316.Google Scholar
  23. 23.
    Sen, C.K. and Packer, L (1999)., Redox Regulation of Cellular Responses by a-lipoic Acid, In: Redox Regulation of Cell signaling and its Clinical Application, Eds: Yodoi, J., and Packer, L., In: Oxidative Stress and Disease Series (eds: Packer, L., and E Cadenas, E.), Marcel Dekker Inc., New York pp 1-328.Google Scholar
  24. 24.
    Sen, C. K., Tirosh, O., Roy, S., Kobayashi, M. S. and Packer, L.(1998)., A positively charged alpha-lipoic acid analogue with increased cellular uptake and more potent immunomodulatory activity, Biochem Biophys Res Commun, 223-228.Google Scholar
  25. 25.
    Sen, C, Roy, S. and Packer, L.(1997), Therapeutic potential of the antioxidant and redox properties of alpha-lipoic acid, In: Oxidative Stress in Cancer, AIDS, and Neurodegenerative Diseases (L. Montagnier, R. Olivier and C. Pasquier, eds.), Marcel Dekker, New York, 251-268.Google Scholar
  26. 26.
    Sies, H.(1985), Oxidative Stress: Introductory remarks, Academic Press,, pp. 1-8.Google Scholar
  27. 27.
    Suzuki, Y. J., Aggarwal, B. B. and Packer, L.(1992), Alpha-lipoic acid is a potent inhibitor of NF-kappa B activation in human T cells, Biochem Biophys Res Commun, 189, 1709–15.CrossRefGoogle Scholar
  28. 28.
    Tirosh, O, Roy, S. and Packer, L.(2002), Lipoic Acid: cellular metabolism, antioxidant activity and cilnical relevance. IN: Handbook of Antioxidants 2nd edition, Enrique Cadenas and Lester Packer (Eds.) Marcel Dekker Inc., New York, pp 473-487.Google Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2003

Authors and Affiliations

  • Lester Packer
    • 1
  1. 1.Department of Molecular Pharmacology and Toxicology School of Pharmacy, Health Sciences CampusUniversity of Southern CaliforniaLos AngelesUSA

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