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

Lookup NU author(s): Dr Audrey Brown, Beth Dibnah, Professor Julia Newton, Professor Mark Walker

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

© 2018 The Author(s). 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 in vitro. 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.


Publication metadata

Author(s): Brown AE, Dibnah B, Fisher E, Newton JL, Walker M

Publication type: Article

Publication status: Published

Journal: Bioscience Reports

Year: 2018

Volume: 38

Issue: 3

Print publication date: 01/06/2018

Online publication date: 13/04/2018

Acceptance date: 04/04/2018

Date deposited: 04/06/2018

ISSN (print): 0144-8463

ISSN (electronic): 1573-4935

Publisher: Portland Press Ltd

URL: https://doi.org/10.1042/BSR20180242

DOI: 10.1042/BSR20180242


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