Abstract
Type 2 diabetes mellitus (T2D) is a metabolic disorder caused by chronic hyperglycemia due to a deficiency in the secretion and/or action of insulin. Zinc (Zn) supplementation and strength exercise increases insulin signaling. We evaluate the effect of Zn supplementation and strength exercise on insulin resistance in the liver of rats with diet-induced T2D through the study of phosphorylation of Akt and protein tyrosine phosphatase 1B (PTP1B). Rats were fed with a high-fat diet (HFD) for 18 weeks to induce T2D and then assigned in four experimental groups: HFD, HFD-Zn (Zn), HFD-strength exercise (Ex), and HFD-Zn/strength exercise (ZnEx) and treated during 12 weeks. Serum Zn, lipid profile, transaminases, glucose, and insulin were measured. In the liver with/without insulin stimuli, total and phosphorylated Akt (pAktSer473) and PTP1B (pPTP1BSer50) were determined by western blot. Hepatic steatosis was evaluated by histological staining with red oil and intrahepatic triglyceride (IHTG) content. There were no differences in biochemical and body-related variables. The ZnEx group showed a higher level of pAkt, both with/without insulin. The ZnEx group also showed higher levels of pPTP1B with respect to HFD and Zn groups. The ZnEx group had higher levels of pPTP1B than groups treated with insulin. Liver histology showed a better integrity and less IHTG in Ex and ZnEx with respect to the HFD group. The Ex and ZnEx groups had lower IHTG with respect to the HFD group. Our results showed that Zn supplementation and strength exercise together improved insulin signaling and attenuated nonalcoholic liver disease in a T2D rat model.
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Acknowledgments
The authors sincerely acknowledge the technical support for rat diet preparation of the following undergraduate students: JF Orellana, P Meneses, C Espinoza, R Farias, M Muñoz, and A Rivas, from the School of Nutrition and Dietetics (Universidad de Chile). The authors also acknowledge the contribution of Marcelo Cano, PhD, and Alex Barham, MSc, for implementing the exercise protocol.
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This work was supported by the National Commission for Research in Science and Technology (CONICYT), research project FONDECYT 1160792
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AV, MRu, and MAO conceptualized and designed the research. AV, KM, AE, JC, JI, and KV performed the experiments. AV, MRi, and MAO analyzed the data. AV, MRi, MRu, and MAO interpreted the results of experiments. AV, MRi, and MAO prepared the figures. AV and MA drafted the manuscript. MRu and MAO edited and revised the manuscript. MAO and MRu approved the final version of manuscript.
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Manuel Ruz, Jorge Inostroza, Diego García, and Miguel Arredondo received payment from the research project FONDECYT 1160792 that funded this study. The rest of authors declare that they have no conflicts of interest.
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Animal experiments were performed in accordance with animal protection regulations of the Faculty of Medicine, University of Chile. The protocol was approved by the Bioethics Committee, Faculty of Medicine, University of Chile.
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Vivero, A., Ruz, M., Rivera, M. et al. Zinc Supplementation and Strength Exercise in Rats with Type 2 Diabetes: Akt and PTP1B Phosphorylation in Nonalcoholic Fatty Liver. Biol Trace Elem Res 199, 2215–2224 (2021). https://doi.org/10.1007/s12011-020-02324-3
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DOI: https://doi.org/10.1007/s12011-020-02324-3