Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, U.K.
Clinical Academic Office, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, U.K.
Biosci Rep. 2018 May 8;38(3). doi: 10.1042/BSR20180242. Print 2018 Jun 29.
Skeletal muscle fatigue and post-exertional malaise are key symptoms of myalgic encephalomyelitis (ME)/chronic fatigue syndrome (ME/CFS). We have previously shown that AMP-activated protein kinase (AMPK) activation and glucose uptake are impaired in primary human skeletal muscle cell cultures derived from patients with ME/CFS in response to electrical pulse stimulation (EPS), a method which induces contraction of muscle cells The aim of the present study was to assess if AMPK could be activated pharmacologically in ME/CFS. Primary skeletal muscle cell cultures from patients with ME/CFS and healthy controls were treated with either metformin or compound 991. AMPK activation was assessed by Western blot and glucose uptake measured. Both metformin and 991 treatment significantly increased AMPK activation and glucose uptake in muscle cell cultures from both controls and ME/CFS. Cellular ATP content was unaffected by treatment although ATP content was significantly decreased in ME/CFS compared with controls. Pharmacological activation of AMPK can improve glucose uptake in muscle cell cultures from patients with ME/CFS. This suggests that the failure of EPS to activate AMPK in these muscle cultures is due to a defect proximal to AMPK. Further work is required to delineate the defect and determine whether pharmacological activation of AMPK improves muscle function in patients with ME/CFS.
骨骼肌疲劳和运动后不适是肌痛性脑脊髓炎（ME）/慢性疲劳综合征（ME/CFS）的主要症状。我们之前已经表明，对电脉冲刺激（EPS）的反应中，源自 ME/CFS 患者的原代人骨骼肌细胞培养物中的 AMP 激活蛋白激酶（AMPK）激活和葡萄糖摄取受损，EPS 是一种诱导肌肉细胞收缩的方法。本研究的目的是评估 AMPK 是否可以通过药理学方法在 ME/CFS 中被激活。用二甲双胍或化合物 991 处理源自 ME/CFS 患者和健康对照者的原代骨骼肌细胞培养物。通过 Western blot 评估 AMPK 激活情况，并测量葡萄糖摄取量。二甲双胍和 991 处理均显著增加了对照者和 ME/CFS 患者骨骼肌细胞培养物中的 AMPK 激活和葡萄糖摄取。尽管与对照者相比，ME/CFS 中的细胞 ATP 含量明显降低，但处理对细胞 ATP 含量没有影响。在这些肌肉培养物中，EPS 不能激活 AMPK，这表明 AMPK 的激活失败是由于 AMPK 近端的缺陷所致。需要进一步的工作来阐明缺陷，并确定 AMPK 的药理学激活是否可以改善 ME/CFS 患者的肌肉功能。
