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Effect of thiol antioxidant on body fat and insulin reactivity

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Abstract

Insulin signaling is enhanced by moderate concentrations of reactive oxygen species (ROS) and suppressed by persistent exposure to ROS. Diabetic patients show abnormally high ROS levels and a decrease in insulin reactivity which is ameliorated by antioxidants, such as N-acetylcysteine (NAC). A similar effect of NAC has not been reported for non-diabetic subjects. We now show that the insulin receptor (IR) kinase is inhibited in cell culture by physiologic concentrations of cysteine. In two double-blind trials involving a total of 140 non-diabetic subjects we found furthermore that NAC increased the HOMA-R index (derived from the fasting insulin and glucose concentrations) in smokers and obese patients, but not in nonobese non-smokers. In obese patients NAC also caused a decrease in glucose tolerance and body fat mass. Simultaneous treatment with creatine, a metabolite utilized by skeletal muscle and brain for the interconversion of ADP and ATP, reversed the NAC-mediated increase in HOMA-R index and the decrease in glucose tolerance without preventing the decrease in body fat. As the obese and hyperlipidemic patients had lower plasma thiol concentrations than the normolipidemic subjects, our results suggest that low thiol levels facilitate the development of obesity. Supplementation of thiols plus creatine may reduce body fat without compromising glucose tolerance.

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Abbreviations

C :

Creatine

HL-NSM :

Hyperlipidemic non-smokers

HL-SM :

Hyperlipidemic smokers

IR :

Insulin receptor

MBP :

Myelin basic protein

NAC :

N-Acetylcysteine

NL-NSM :

Normolipidemic non-smokers

NL-SM :

Normolipidemic smokers

OGTT :

Oral glucose tolerance test

P C :

PlaceboCreatine

P N :

PlaceboNAC

ROS :

Reactive oxygen species

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Acknowledgements

We thank Dr. L. Edler for assistance in the statistical analysis, Mrs. U. Winter and Mr. H. Lips for technical assistance, Mrs. C. Contesse for assistance in the recruitment process, and Mrs. I. Fryson for assistance in the preparation of this manuscript. The studies were funded by the Division of Immunochemistry of the German Cancer Research Center, Germany (Head: W.D.)

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Authors and Affiliations

  1. Division of Immunochemistry, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, 69120 , Heidelberg, Germany

    Wulf Hildebrandt, Holger Krakowski-Roosen, Roland Sauer, Sabrina Lacher, Nuria Nöbel & Wulf Dröge

  2. Department of Internal Medicine I, Division of Endocrinology and Metabolism, Medical University Clinic, University of Heidelberg, Bergheimer Strasse 58, 69115 , Heidelberg, Germany

    Andreas Hamann, Klaus Dugi, Anne Bodens, Vassiliki Bellou & Peter Nawroth

  3. Department of Anatomy and Cell Biology III, University of Heidelberg, Im Neuenheimer Feld 307, 69120 , Heidelberg, Germany

    Ralf Kinscherf

  4. Biostatistics Unit, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, 69120 , Heidelberg, Germany

    Lutz Edler

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  1. Wulf Hildebrandt
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Correspondence to Wulf Dröge.

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Hildebrandt, W., Hamann, A., Krakowski-Roosen, H. et al. Effect of thiol antioxidant on body fat and insulin reactivity. J Mol Med 82, 336–344 (2004). https://doi.org/10.1007/s00109-004-0532-5

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  • DOI: https://doi.org/10.1007/s00109-004-0532-5

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