Research abstract:
Pharmacological activation of AMPK and glucose uptake in cultured human skeletal muscle cells from patients with ME/CFS, by Audrey E Brown, Beth Dibnah, Emily Fisher, Julia L Newton, Mark Walker in Bioscience Reports [Preprint April 13, 2018]
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 [antifungal] 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.
