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Modulation of Zinc Transporter Expressions by Additional Zinc in C2C12 Cells Cultured in a High Glucose Environment and in the Presence of Insulin or Interleukin-6

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Abstract

Zn status has been related to various chronic diseases presenting oxidative stress and inflammation, such as type 2 diabetes. Zn supplementation has been suggested to be a potential coadjuvant in the management of this condition. Zn transporters constitute a key component in the maintenance of Zn homeostasis. Our aim was to evaluate the modulatory effect of additional Zn (10 or 100 µM; as a ZnSO4*7H20) on the mRNA relative expression of selected Zn transporters (ZnT1, ZnT5, ZnT7, ZIP6, ZIP7, ZIP10, ZIP14), in myoblast (C2C12) cells cultured in normal (10 mM) and high glucose (30 mM), and in the absence or presence of insulin (1 nM), and interleukin-6 (IL-6; 5 nM) for 24 h. The main findings of our study were that in high glucose conditions in absence of insulin or IL-6, additional Zn increased ZnT1 and ZIP6, and decreased ZnT5 and ZIP7 expressions. However, this situation is modified by insulin, where incremental Zn induced increased expressions of ZnT1, ZnT5, and all the ZIP transporters studied. In high glucose conditions and in the presence of IL-6, additional Zn caused increased expressions of ZnT7, ZIP7, and ZIP14, compared with results in the absence of IL-6. This study provides preliminary evidence for the differential expression of selected Zn transporters in C2C12 cells subjected to high glucose and incremental Zn, suggesting that important changes in intracellular Zn distribution take place in response to inflammatory and high-insulin environments. Further study is necessary to understand the implications of these findings.

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Funding

This research was funded by the National Fund for Science and Technological Development (FONDECYT) Chile, grant number 1120323.

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Authors and Affiliations

  1. Department of Nutrition, Faculty of Medicine, University of Chile, Avenida Independencia 1027, Independencia, Santiago, Chile

    Manuel Ruz

  2. Micronutrient Laboratory, Institute of Nutrition and Food Technology, University of Chile, Macul 5540, Macul, Santiago, Chile

    Mónica Andrews-Guzmán & Miguel Arredondo-Olguín

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  1. Manuel Ruz
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Contributions

MR, MAG, and MAO: conception and design of research. MAG: performed experiments. MAG and MAO: analyzed data. MAG, MR, and MAO: interpreted results of experiments. MAG and MAO: prepared figures. MAG: drafted manuscript. MAG, MR, and MAO: edited and revised manuscript. MAO and MR: approved the final version of the manuscript.

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Correspondence to Miguel Arredondo-Olguín.

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This article is based on previously conducted studies and does not contain any studies with human participants or animals performed by any of the authors.

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Manuel Ruz and Miguel Arredondo received stipends from the research project FONDECYT 1120323. The rest of the authors declare that they have no conflicts of interest.

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Ruz, M., Andrews-Guzmán, M. & Arredondo-Olguín, M. Modulation of Zinc Transporter Expressions by Additional Zinc in C2C12 Cells Cultured in a High Glucose Environment and in the Presence of Insulin or Interleukin-6. Biol Trace Elem Res 201, 3428–3437 (2023). https://doi.org/10.1007/s12011-022-03443-9

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