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.

中文翻译：

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使用肉毒杆菌毒素的化学去神经作用可增加Akt表达，并减少胰岛素在小鼠肌肉中最大程度地刺激葡萄糖的转运。

肉毒杆菌毒素A（肉毒杆菌毒素）是用于痉挛治疗和美容目的的毒素。肉毒杆菌毒素通过阻止乙酰胆碱从运动神经的释放来阻止骨骼肌纤维的兴奋，这一过程被称为化学去神经。手术神经支配与规范的胰岛素激活激酶Akt的表达增加，葡萄糖处理蛋白GLUT4和己糖激酶II（HKII）的表达降低以及胰岛素抵抗性葡萄糖摄取有关，但尚不清楚肉毒杆菌是否具有类似的作用。为了测试这一点，我们在离体小鼠比目鱼体内使用超最大胰岛素刺激进行了时程研究。尽管GLUT4，HKII的表达和TBC1D4的表达和磷酸化程度较低，但在肌肉注射肉毒杆菌注射后第1、7和21天，葡萄糖转运反应性均未见影响。肉毒杆菌毒素治疗在第21天增加了Akt蛋白的表达和上游激酶Akt的磷酸化。在一项后续研究中，肉毒杆菌毒素降低了胰岛素刺激的最大葡萄糖转运。肉毒杆菌毒素治疗潜在的关注是胰岛素信号，GLUT4和HKII的显着改变以及胰岛素刺激的葡萄糖转运不足，值得进一步研究。此外，肉毒杆菌引起的化学去神经模型可能是手术去神经的侵入性较小的替代方法。GLUT4和HKII以及胰岛素刺激下的最大葡萄糖转运是肉毒杆菌毒素治疗的潜在问题，值得对人体肌肉进行进一步研究。此外，肉毒杆菌引起的化学去神经模型可能是手术去神经的侵入性较小的替代方法。GLUT4和HKII以及胰岛素刺激下的最大葡萄糖转运是肉毒杆菌毒素治疗的潜在问题，值得对人体肌肉进行进一步研究。此外，肉毒杆菌引起的化学去神经模型可能是手术去神经的侵入性较小的替代方法。