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Malondialdehyde but Not Methylglyoxal Impairs Insulin Signaling, NO Production, and Endothelial Barrier

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Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology Aims and scope

Abstract

Dyslipidemia and hyperglycemia portray “cause-and-consequence” of type 2 diabetes mellitus (T2DM). They are linked to malondialdehyde (MDA) and methylglyoxal (MGO) generation that result from membrane lipid peroxidation and oxidative glucose conversions. We compared the effects of exogenous MDA and MGO on human umbilical vein endothelial cells and found that MDA but not MGO impairs insulin activation of PI3-kinase pathway, NO production, and endothelial barrier capacity. MDA abolished insulin activation of Akt and eNOS but not that of IRS. These results substantiate the hypothesis that MDA may be involved in endothelial dysfunction as an early event in the development of T2DM.

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ACKNOWLEDGMENTS

The work was supported by the Russian Science Foundation (project no.19-15-00361) for ECIS experiments and by the Russian Foundation for Basic Research (project no. 18-315-00377) for other experiments. The authors thank T.N. Vlasik and E.E. Efremov for providing the anti-MDA and anti-MGO antibodies.

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Authors and Affiliations

  1. National Medical Research Center for Cardiology, Institute of Experimental Cardiology, 121552, Moscow, Russia

    M. V. Samsonov, N. V. Podkuychenko, A. V. Vorotnikov & V. P. Shirinsky

  2. National Medical Research Center for Cardiology, Institute of Clinical Cardiology, 121552, Moscow, Russia

    V. Z. Lankin

Authors
  1. M. V. Samsonov
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  2. N. V. Podkuychenko
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  3. V. Z. Lankin
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  4. A. V. Vorotnikov
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  5. V. P. Shirinsky
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Correspondence to A. V. Vorotnikov or V. P. Shirinsky.

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This article does not contain any studies involving animals or human participants performed by any of the authors.

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Translated by A. Vorotnikov

Abbreviations: DAF, 4-amino-5-methylamino-2',7'-difluorofluorescein; EBM, endothelial basal medium; EGM, endothelial growth medium; eNOS, endothelial NO-synthase; FFA, free fatty acid; HUVEC, human umbilical vein endothelial cells; MDA, malondialdehyde; MGO, methylglyoxal; ROS, reactive oxygen species; TER, transendothelial electric resistance; T2DM, type 2 diabetes mellitus.

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Samsonov, M.V., Podkuychenko, N.V., Lankin, V.Z. et al. Malondialdehyde but Not Methylglyoxal Impairs Insulin Signaling, NO Production, and Endothelial Barrier. Biochem. Moscow Suppl. Ser. A 15, 195–200 (2021). https://doi.org/10.1134/S1990747821030089

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  • DOI: https://doi.org/10.1134/S1990747821030089

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