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

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  • Additional Information
    • Source:
      Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE
    • Publication Information:
      Original Publication: London : Nature Publishing Group, copyright 2011-
    • Subject Terms:
      Glucose Transporter Type 4/*metabolism ; Insulin/*pharmacology ; Muscle Cells/*drug effects ; SUMO-1 Protein/*metabolism; Animals ; Cell Line ; Humans ; Hypoglycemic Agents/pharmacology ; Insulin Resistance ; Models, Biological ; Muscle Cells/cytology ; Muscle Cells/metabolism ; Muscle, Skeletal/cytology ; Muscle, Skeletal/metabolism ; Protein Transport/drug effects ; Rats ; Signal Transduction/drug effects ; Sumoylation/drug effects
    • 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.
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    • Grant Information:
      200581/Z/16/Z United Kingdom WT_ Wellcome Trust
    • Accession Number:
      0 (Glucose Transporter Type 4)
      0 (Hypoglycemic Agents)
      0 (Insulin)
      0 (SUMO-1 Protein)
    • Publication Date:
      Date Created: 20190426 Date Completed: 20201019 Latest Revision: 20210109
    • Publication Date:
      20231215
    • Accession Number:
      PMC6482176
    • Accession Number:
      10.1038/s41598-019-42574-3
    • Accession Number:
      31019221