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The role of mitochondrial DNA damage at skeletal muscle oxidative stress on the development of type 2 diabetes

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Abstract

Reduced cellular response to insulin in skeletal muscle is one of the major components of the development of type 2 diabetes (T2D). Mitochondrial dysfunction involves in the accumulation of toxic reactive oxygen species (ROS) that leads to insulin resistance. The aim of this study was to verify the involvement of mitochondrial DNA damage at ROS generation in skeletal muscle during development of T2D. Wistar rats were fed a diet containing 60% fat over 8 weeks and at day 14 a single injection of STZ (25 mg/kg) was administered (T2D-induced). Control rats received standard food and an injection of citrate buffer. Blood and soleus muscle were collected. Abdominal fat was quantified as well as glucose, triglyceride, LDL, HDL, and total cholesterol in plasma and mtDNA copy number, cytochrome b (cytb) mRNA, 8-hydroxyguanosine, and 8-isoprostane (a marker of ROS) in soleus muscle. T2D-induced animal presented similar characteristics to humans that develop T2D such as changes in blood glucose, abdominal fat, LDL, HDL and cholesterol total. In soleus muscle 8-isoprostane, mtDNA copy number and 8-hydroxyguanosine were increased, while cytb mRNA was decreased in T2D. Our results suggest that in the development of T2D, when risks factors of T2D are present, intracellular oxidative stress increases in skeletal muscle and is associated with a decrease in cytb transcription. To overcome this process mtDNA increased but due to the proximity of ROS generation, mtDNA remains damaged by oxidation leading to an increase in ROS in a vicious cycle accounting to the development of insulin resistance and further T2D.

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Acknowledgements

The authors would like to thanks the National Council for Scientific and Technological Development for the grant support (CNPq-301744/2014-9). Also, we would like Prof. Edésio Fialho dos Rei to provide the PCR equipment and Jefferson Fernando Naves Pinto for the technical support.

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Authors and Affiliations

  1. Instituto de Biociências, Federal University of Jataí, Jataí, Goias, Brazil

    Denise Silva de Oliveira & Sandra Aparecida Benite-Ribeiro

  2. Pós-Graduação em Biociência Animal, Federal University of Jataí, Jataí, Goias, Brazil

    Sandra Aparecida Benite-Ribeiro

  3. Pós-Graduação em Ciência da Saúde, Federal University of Jataí, Jataí, Goias, Brazil

    Julia Matzenbacher dos Santos, Marcos Lazaro Moreli & Sandra Aparecida Benite-Ribeiro

  4. Detroit R&D, Inc, 2727 2nd street, 4113, Detroit, Michigan, 48201, USA

    Julia Matzenbacher dos Santos

  5. Science and Math Department, Henry Ford College, Dearborn, MI, USA

    Julia Matzenbacher dos Santos

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  1. Julia Matzenbacher dos Santos
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  2. Denise Silva de Oliveira
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  3. Marcos Lazaro Moreli
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  4. Sandra Aparecida Benite-Ribeiro
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Correspondence to Julia Matzenbacher dos Santos or Sandra Aparecida Benite-Ribeiro.

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dos Santos, J.M., de Oliveira, D.S., Moreli, M.L. et al. The role of mitochondrial DNA damage at skeletal muscle oxidative stress on the development of type 2 diabetes. Mol Cell Biochem 449, 251–255 (2018). https://doi.org/10.1007/s11010-018-3361-5

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  • DOI: https://doi.org/10.1007/s11010-018-3361-5

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