Chemical denervation using botulinum toxin increases Akt expression and reduces submaximal insulin-stimulated glucose transport in mouse muscle

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Zhencheng Li, Lui Näslund-Koch, Carlos Henriquez Olguín, Jonas Roland Knudsen, Jingwen Li, Agnete Louise Bjerregaard Madsen, Satoru Ato, Jacob Wienecke, Riki Ogasawara, Jens Bo Nielsen, Thomas Elbenhardt Jensen

Botulinum toxin A (botox) is a toxin used for spasticity treatment and cosmetic purposes. Botox blocks the excitation of skeletal muscle fibers by preventing the release of acetylcholine from motor nerves, a process termed chemical denervation. Surgical denervation is associated with increased expression of the canonical insulin-activated kinase Akt, lower expression of glucose handling proteins GLUT4 and hexokinase II (HKII) and insulin resistant glucose uptake, but it is not known if botox has a similar effect. To test this, we performed a time-course study using supra-maximal insulin-stimulation in mouse soleus ex vivo. No effect was observed in the glucose transport responsiveness at day 1, 7 and 21 after intramuscular botox injection, despite lower expression of GLUT4, HKII and expression and phosphorylation of TBC1D4. Akt protein expression and phosphorylation of the upstream kinase Akt were increased by botox treatment at day 21. In a follow-up study, botox decreased submaximal insulin-stimulated glucose transport. The marked alterations of insulin signaling, GLUT4 and HKII and submaximal insulin-stimulated glucose transport are a potential concern with botox treatment which merit further investigation in human muscle. Furthermore, the botox-induced chemical denervation model may be a less invasive alternative to surgical denervation.

Original languageEnglish
JournalCellular Signalling
Volume53
Pages (from-to)224-233
Number of pages10
ISSN0898-6568
DOIs
Publication statusPublished - Jan 2019

    Research areas

  • The Faculty of Science - Atrophy, GLUT4, Hexokinase, TBC1D4, Insulin signaling, Bolulinum toxin (Botox)
  • Atrophy, GLUT4, Hexokinase, Insulin signaling, TBC1D4

ID: 204307218