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Insulin-dependent GLUT4 trafficking is not regulated by protein SUMOylation in L6 myocytes

Carmichael, Ruth E.; Wilkinson, Kevin A.; Craig, Tim J.

Insulin-dependent GLUT4 trafficking is not regulated by protein SUMOylation in L6 myocytes Thumbnail


Authors

Ruth E. Carmichael

Kevin A. Wilkinson

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Dr Tim Craig Tim.Craig@uwe.ac.uk
Associate Professor of Neuroscience



Abstract

Type-II Diabetes Mellitus (T2DM) is one of the fastest growing public health issues today, consuming 12% of worldwide health budgets and affecting an estimated 400 million people. One of the key pathological traits of this disease is insulin resistance at ‘glucose sink’ tissues (mostly skeletal muscle), and this remains one of the features of this disease most intractable to therapeutic intervention. Several lines of evidence have implicated the post-translational modification,
SUMOylation, in insulin signalling and insulin resistance in skeletal muscle. In this study, we examined this possibility by manipulation of cellular SUMOylation levels using multiple different tools, and assaying the effect on insulin-stimulated GLUT4 surface expression in differentiated L6 rat myocytes. Although insulin stimulation of L6 myocytes produced a robust decrease in total cellular SUMO1-ylation levels, manipulating cellular SUMOylation had no effect on insulin-responsive GLUT4 surface trafficking using any of the tools we employed. Whilst we cannot totally exclude the possibility that SUMOylation plays a role in the insulin signalling pathway in human health and disease, our data strongly argue that GLUT4 trafficking in response to insulin is not regulated by protein SUMOylation, and that SUMOylation does not therefore represent a viable therapeutic target for the treatment of insulin resistance.

Citation

Carmichael, R. E., Wilkinson, K. A., & Craig, T. J. (2019). Insulin-dependent GLUT4 trafficking is not regulated by protein SUMOylation in L6 myocytes. Scientific Reports, 9(1), Article 6477. https://doi.org/10.1038/s41598-019-42574-3

Journal Article Type Article
Acceptance Date Feb 6, 2019
Online Publication Date Apr 24, 2019
Publication Date Dec 1, 2019
Deposit Date Feb 19, 2019
Publicly Available Date Mar 29, 2024
Journal Scientific Reports
Electronic ISSN 2045-2322
Publisher Nature Research (part of Springer Nature)
Peer Reviewed Peer Reviewed
Volume 9
Issue 1
Article Number 6477
DOI https://doi.org/10.1038/s41598-019-42574-3
Keywords diabetes, GLUT4, insulin, SUMOylation
Public URL https://uwe-repository.worktribe.com/output/847681
Publisher URL https://doi.org/10.1038/s41598-019-42574-3

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