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Chromium malate alleviates high-glucose and insulin resistance in L6 skeletal muscle cells by regulating glucose uptake and insulin sensitivity signaling pathways

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Abstract

Previous study revealed that chromium malate improved the regulation of fasting blood glucose and insulin resistance in type 2 diabetic rats. In this study, the effect of chromium malate on anti-high-glucose and improve insulin resistance activities in L6 skeletal muscle cells with insulin resistance and its acting mechanism were investigated. Chromium malate showed direct anti-high-glucose activity in vitro. The glucose levels had a significant downward trend compared to chromium trichloride. Compared with model group, chromium malate could significantly promote the secretion levels of GLUT-4, Akt, Irs-1, PPARγ, PI3K and p38-MAPK, promote AMPKβ1 phosphorylation, and reduced the level of p-Irs-1 in L6 cells with insulin resistance. And the relate mRNA expression of chromium malate was significantly increased. Chromium malate is more effective at improving the related proteins and mRNA expression than those of chromium trichloride and chromium picolinate. Pretreatment with the specific p38MAPK inhibitor completely inhibited the GLUT-4 and Irs-1 proteins and mRNA expression induced by the chromium malate when compared with model group, but GLUT-4 and Irs-1 proteins and mRNA expression was partially inhibited after inhibiting p38MAPK/PI3K expression. The results suggested that chromium malate had a beneficial influence on the improvement of controlling glucose levels and insulin resistance in L6 cells with insulin resistance by regulating proteins production and genes expression in glucose uptake and insulin sensitivity signaling pathways.

Graphical abstract

The signaling pathways of glucose uptake and insulin sensitivity. This study shown that chromium malate could significant increase in the production levels of GLUT-4, p-AMPKβ1, Akt, Irs-1, PPARγ, PI3K and p38-MAPK proteins and mRNA in L6 cells with insulin resistant. Pretreatment with the specific p38MAPK inhibitor completely inhibited the GLUT-4 and Irs-1 proteins and mRNA expression induced by the chromium malate compared to model group, but the proteins and mRNA were partially inhibited after inhibiting p38MAPK/PI3K. Therefore, chromium malate had beneficial influence on improvement of controlling glucose levels and insulin resistant in L6 cells by regulating proteins production and genes expression in glucose uptake and insulin sensitivity signaling pathways. The key proteins of glucose uptake and insulin sensitivity signaling pathways were p38MAPK, PI3K and PPARγ.

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Acknowledgements

This work was supported by the Specialized Research Fund for the Natural Science Foundation of China (Grant Numbers 31271850) and Research Foundation for Advanced Talents of Jiangsu University (Grant Numbers 15JDG146).

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Author notes

  1. Weiwei Feng and Yangyang Ding contributed to this article equally and are co-first authors.

Authors and Affiliations

  1. School of the Environment and Safety Engineering, Jiangsu University, 301 Xuefu Rd., Zhenjiang, 212013, Jiangsu, China

    Weiwei Feng, Yangyang Ding, Yao Chen, Hui Chen, Guanghua Mao & Xiangyang Wu

  2. Institute of Environmental Health and Ecological Security, Jiangsu University, Zhenjiang, Jiangsu, China

    Weiwei Feng & Xiangyang Wu

  3. School of Food and Biological Engineering, Jiangsu University, 301 Xuefu Rd., Zhenjiang, 212013, Jiangsu, China

    Weijie Zhang, Qian Li & Wei Wang

  4. School of Medical Science and Laboratory Medicine, Jiangsu University, 301 Xuefu Rd., Zhenjiang, 212013, Jiangsu, China

    Yun Feng

  5. School of Chemistry and Chemical Engineering, Jiangsu University, 301 Xuefu Rd., Zhenjiang, 212013, Jiangsu, China

    Ting Zhao & Liuqing Yang

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  1. Weiwei Feng
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Feng, W., Ding, Y., Zhang, W. et al. Chromium malate alleviates high-glucose and insulin resistance in L6 skeletal muscle cells by regulating glucose uptake and insulin sensitivity signaling pathways. Biometals 31, 891–908 (2018). https://doi.org/10.1007/s10534-018-0132-4

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