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

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 derive...

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Veröffentlicht in:Bioscience reports 2018-06, Vol.38 (3)
Hauptverfasser: Brown, Audrey E, Dibnah, Beth, Fisher, Emily, Newton, Julia L, Walker, Mark
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creator Brown, Audrey E
Dibnah, Beth
Fisher, Emily
Newton, Julia L
Walker, Mark
description 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.
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subjects Adult
AMP-Activated Protein Kinase Kinases
Biopsy
Carbohydrate Metabolism - drug effects
Carbohydrate Metabolism - radiation effects
Cell Culture Techniques
Electric Stimulation
Fatigue Syndrome, Chronic - drug therapy
Fatigue Syndrome, Chronic - physiopathology
Female
Glucose - metabolism
Humans
Male
Metformin - pharmacology
Muscle Contraction - drug effects
Muscle Contraction - radiation effects
Muscle, Skeletal - drug effects
Muscle, Skeletal - metabolism
Muscle, Skeletal - pathology
Muscle, Skeletal - radiation effects
Protein Kinases - genetics
Protein Kinases - radiation effects
title Pharmacological activation of AMPK and glucose uptake in cultured human skeletal muscle cells from patients with ME/CFS
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