Chemical denervation using botulinum toxin increases Akt expression and reduces submaximal insulin-stimulated glucose transport in mouse muscle
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Chemical denervation using botulinum toxin increases Akt expression and reduces submaximal insulin-stimulated glucose transport in mouse muscle. / Li, Zhencheng; Näslund-Koch, Lui; Henriquez Olguín, Carlos ; Knudsen, Jonas Roland; Li, Jingwen; Madsen, Agnete Louise Bjerregaard; Ato, Satoru; Wienecke, Jacob; Ogasawara, Riki; Nielsen, Jens Bo; Jensen, Thomas Elbenhardt.
In: Cellular Signalling, Vol. 53, 01.2019, p. 224-233.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Chemical denervation using botulinum toxin increases Akt expression and reduces submaximal insulin-stimulated glucose transport in mouse muscle
AU - Li, Zhencheng
AU - Näslund-Koch, Lui
AU - Henriquez Olguín, Carlos
AU - Knudsen, Jonas Roland
AU - Li, Jingwen
AU - Madsen, Agnete Louise Bjerregaard
AU - Ato, Satoru
AU - Wienecke, Jacob
AU - Ogasawara, Riki
AU - Nielsen, Jens Bo
AU - Jensen, Thomas Elbenhardt
N1 - CURIS 2019 NEXS 003
PY - 2019/1
Y1 - 2019/1
N2 - 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.
AB - 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.
KW - Faculty of Science
KW - Atrophy
KW - GLUT4
KW - Hexokinase
KW - TBC1D4
KW - Insulin signaling
KW - Bolulinum toxin (Botox)
KW - Atrophy
KW - GLUT4
KW - Hexokinase
KW - Insulin signaling
KW - TBC1D4
U2 - 10.1016/j.cellsig.2018.10.014
DO - 10.1016/j.cellsig.2018.10.014
M3 - Journal article
C2 - 30352253
VL - 53
SP - 224
EP - 233
JO - Cellular Signalling
JF - Cellular Signalling
SN - 0898-6568
ER -
ID: 204307218