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Amelioration of High-Insulin-Induced Skeletal Muscle Cell Insulin Resistance by Resveratrol Is Linked to Activation of AMPK and Restoration of GLUT4 Translocation

by Filip Vlavcheski 1,2,†, Danja J. Den Hartogh 1,2,†, Adria Giacca 3,4,5,6 and Evangelia Tsiani 1,2,*
1
Department of Health Sciences, Brock University, St. Catharines, ON L2S 3A1, Canada
2
Centre for Bone and Muscle Health, Brock University, St. Catharines, ON L2S 3A1, Canada
3
Department of Physiology, University of Toronto, Toronto, ON M5S 1A8, Canada
4
Department of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada
5
Institute of Medical Sciences, University of Toronto, Toronto, ON M5S 1A8T, Canada
6
Banting and Best Diabetes Centre, University of Toronto, Toronto, ON M5G 2C4, Canada
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Nutrients 2020, 12(4), 914; https://doi.org/10.3390/nu12040914 (registering DOI)
Received: 29 February 2020 / Revised: 17 March 2020 / Accepted: 23 March 2020 / Published: 27 March 2020
(This article belongs to the Section Nutrition and Metabolism)
Insulin resistance, the hallmark of type 2 diabetes mellitus (T2DM), is linked to hyperinsulinemia, which develops to counterbalance initial peripheral hormone resistance. Studies indicate that chronically elevated levels of insulin lead to skeletal muscle insulin resistance by deregulating steps within the insulin signaling cascade. The polyphenol resveratrol (RSV) has been shown to have antidiabetic properties in vitro and in vivo. In the present study, we examined the effect of RSV on high insulin (HI)-induced insulin resistance in skeletal muscle cells in vitro and investigated the mechanisms involved. Parental and GLUT4myc-overexpressing L6 rat skeletal muscle cells were used. [3H]2-deoxyglucose (2DG) uptake was measured, and total and phosphorylated levels of specific proteins were examined by immunoblotting. Exposure of L6 cells to HI levels (100 nM) for 24 h decreased the acute-insulin-stimulated 2DG uptake, indicating insulin resistance. HI increased ser307 and ser636/639 phosphorylation of IRS-1 (to 184% ± 12% and 225% ± 28.9% of control, with p < 0.001 and p < 0.01, respectively) and increased the phosphorylation levels of mTOR (174% ± 6.7% of control, p < 0.01) and p70 S6K (228% ± 33.5% of control, p < 0.01). Treatment with RSV abolished these HI-induced responses. Furthermore, RSV increased the activation of AMPK and restored the insulin-mediated increase in plasma membrane GLUT4 glucose transporter levels. These data suggest that RSV has a potential to counteract the HI-induced muscle insulin resistance. View Full-Text
Keywords: resveratrol; high insulin; insulin resistance; IRS-1; mTOR; p70 S6K; AMPK; GLUT4 resveratrol; high insulin; insulin resistance; IRS-1; mTOR; p70 S6K; AMPK; GLUT4
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Vlavcheski, F.; Den Hartogh, D.J.; Giacca, A.; Tsiani, E. Amelioration of High-Insulin-Induced Skeletal Muscle Cell Insulin Resistance by Resveratrol Is Linked to Activation of AMPK and Restoration of GLUT4 Translocation. Nutrients 2020, 12, 914.

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