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Preventive effect of oleate on palmitate-induced insulin resistance in skeletal muscle and its mechanism of action

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Abstract

Insulin resistance in skeletal muscle is a feature associated with exposure to an excess of saturated fatty acids such as palmitate. Oleic acid has been shown to blunt palmitate-induced insulin resistance in muscle cells. However, there is no literature available regarding the effect of oleic acid on palmitate-induced insulin resistance in intact muscle. Therefore, this study investigated the effect of oleic acid on palmitate-induced insulin resistance in rat soleus muscle and its underlying mechanisms. For these purposes, oleic acid (1 mM) was administered for 12 h in the absence or presence of palmitate (2 mM). At the end of the experiment, plasmalemmal GLUT4, the phosphorylation of AS160 and Akt-2, and the total expression of these signaling proteins were examined. We found that treatment with palmitate for 12 h reduced insulin-stimulated GLUT4 translocation and the phosphorylation of AS160 and Akt-2. However, the administration of oleic acid fully restored insulin-stimulated GLUT4 translocation (P < 0.05), as well as AS160 and Akt-2 phosphorylation (P < 0.05) despite the continuous presence of palmitate. Wortmannin, an inhibitor of PI3-K, only slightly prevented the oleic acid-induced improvements in insulin-stimulated GLUT4 translocation, and AS160 phosphorylation. However, this treatment completely inhibited the oleic acid-induced improvement in insulin-stimulated Akt-2 phosphorylation. In contrast, the oleic acid-induced improvement in insulin signaling was not affected by compound C, an AMPK specific inhibitor. In conclusion, the results clearly indicate that oleic acid administration alleviates palmitate-induced insulin resistance by promoting GLUT4 translocation in muscle, at least in part, by activating the PI3K pathway.

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Acknowledgements

The authors would like to thank Yarmouk University, Irbid, Jordan, for providing the required facilities and interdisciplinary research environment. We sincerely thank professor David J Dyck from University of Guelph, Ontario, Canada, for his help with the language editing of the manuscript.

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Authors and Affiliations

  1. Department of Basic Medical Sciences, Faculty of Medicine, Yarmouk University, P.O. Box 566, Irbid, 21163, Jordan

    Hakam Alkhateeb

  2. Department of Biology and Biotechnology, Faculty of Science, Hashemite University, Zarqa, Jordan

    Esam Qnais

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  1. Hakam Alkhateeb
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Correspondence to Hakam Alkhateeb.

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Alkhateeb, H., Qnais, E. Preventive effect of oleate on palmitate-induced insulin resistance in skeletal muscle and its mechanism of action. J Physiol Biochem 73, 605–612 (2017). https://doi.org/10.1007/s13105-017-0594-9

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  • DOI: https://doi.org/10.1007/s13105-017-0594-9

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