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 -