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Uncovering the beginning of diabetes: the cellular redox status and oxidative stress as starting players in hyperglycemic damage

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Abstract

Early hyperglycemic insult can lead to permanent, cumulative damage that might be one of the earliest causes for a pre-diabetic situation. Despite this, the early phases of hyperglycemic exposure have been poorly studied. We have previously demonstrated that mitochondrial injury takes place early on upon hyperglycemic exposure. In this work, we demonstrate that just 1 h of hyperglycemic exposure is sufficient to induce increased mitochondrial membrane potential and generation. This is accompanied (and probably caused) by a decrease in the cells’ NAD+/NADH ratio. Furthermore, we show that the modulation of the activity of parallel pathways to glycolysis can alter the effects of hyperglycemic exposure. Activation of the pentose phosphate pathway leads to diminished effects of glucose on the above parameters, either by removing glucose from glycolysis or by NADPH generation. We also demonstrate that the hexosamine pathway inhibition also leads to a decreased effect of excess glucose. So, this work demonstrates the need for increased focus of study on the reductive status of the cell as one of the most important hallmarks of initial hyperglycemic damage.

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Acknowledgments

JST, FVD, APG, and ATV are recipients of a Fundação para a Ciência e a Tecnologia PhD scholarship (SFRH/BD/38467/2007, SFRH/BD/38372/2007, SFRH/BD/44674/2008, and SFRH/BD/44796/2008, respectively). This work received financial support from “Fundacao para a Ciencia e Tecnologia,” Portugal (Projects PTDC/QUI/72826/2006 and PTCD/QUI-BIC/103514/2008), under the frame of “Programa Operacional Tematico Factores de Competitividade (COMPTE) do Quadro Comunitario de Apoio III,” “Fundo Comunitario Europeu (FEDER),” and National funds.

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Authors and Affiliations

  1. Faculty of Science and Technology, Center for Neuroscience and Cell Biology, University of Coimbra, 3004–517, Coimbra, Portugal

    João Soeiro Teodoro, Ana Patrícia Gomes, Ana Teresa Varela, Filipe Valente Duarte, Anabela Pinto Rolo & Carlos Marques Palmeira

  2. Department of Biology, University of Aveiro, 3810–193, Aveiro, Portugal

    Anabela Pinto Rolo

  3. Department of Life Sciences, Faculty of Science and Technology, University of Coimbra, 3004–517, Coimbra, Portugal

    João Soeiro Teodoro, Ana Patrícia Gomes, Ana Teresa Varela, Filipe Valente Duarte & Carlos Marques Palmeira

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  1. João Soeiro Teodoro
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Correspondence to Carlos Marques Palmeira.

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Teodoro, J.S., Gomes, A.P., Varela, A.T. et al. Uncovering the beginning of diabetes: the cellular redox status and oxidative stress as starting players in hyperglycemic damage. Mol Cell Biochem 376, 103–110 (2013). https://doi.org/10.1007/s11010-012-1555-9

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