Pharmacological activation of AMPK and glucose uptake in cultured human skeletal muscle cells from patients with ME/CFS

Background Skeletal muscle fatigue and post-exertional malaise are key symptoms of Myalgic Encephalomyelitis ( ME/CFS). We have previously shown that 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, a method which induces contraction of muscle cells in vitro. The aim of this study was to assess if AMPK could be activated pharmacologically in ME/CFS. Methods Primary skeletal muscle cell cultures from patients with ME/CFS and healthy controls were treated with either metformin or 991. AMPK activation was assessed by Western blot and glucose uptake measured. Results 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 to controls. Conclusions Pharmacological activation of AMPK can improve glucose uptake in muscle cell cultures from patients with ME/CFS. This suggests that the failure of electrical pulse stimulation 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