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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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Detalles Bibliográficos
Autores principales: Brown, Audrey E., Dibnah, Beth, Fisher, Emily, Newton, Julia L., Walker, Mark
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Portland Press Ltd. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5938427/
https://www.ncbi.nlm.nih.gov/pubmed/29654166
http://dx.doi.org/10.1042/BSR20180242
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author Brown, Audrey E.
Dibnah, Beth
Fisher, Emily
Newton, Julia L.
Walker, Mark
author_facet Brown, Audrey E.
Dibnah, Beth
Fisher, Emily
Newton, Julia L.
Walker, Mark
author_sort Brown, Audrey E.
collection PubMed
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 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.
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spelling pubmed-59384272018-05-15 Pharmacological activation of AMPK and glucose uptake in cultured human skeletal muscle cells from patients with ME/CFS Brown, Audrey E. Dibnah, Beth Fisher, Emily Newton, Julia L. Walker, Mark Biosci Rep Research Articles 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. Portland Press Ltd. 2018-05-08 /pmc/articles/PMC5938427/ /pubmed/29654166 http://dx.doi.org/10.1042/BSR20180242 Text en © 2018 The Author(s). http://creativecommons.org/licenses/by/4.0/This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY) (http://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Articles
Brown, Audrey E.
Dibnah, Beth
Fisher, Emily
Newton, Julia L.
Walker, Mark
Pharmacological activation of AMPK and glucose uptake in cultured human skeletal muscle cells from patients with ME/CFS
title Pharmacological activation of AMPK and glucose uptake in cultured human skeletal muscle cells from patients with ME/CFS
title_full Pharmacological activation of AMPK and glucose uptake in cultured human skeletal muscle cells from patients with ME/CFS
title_fullStr Pharmacological activation of AMPK and glucose uptake in cultured human skeletal muscle cells from patients with ME/CFS
title_full_unstemmed Pharmacological activation of AMPK and glucose uptake in cultured human skeletal muscle cells from patients with ME/CFS
title_short Pharmacological activation of AMPK and glucose uptake in cultured human skeletal muscle cells from patients with ME/CFS
title_sort pharmacological activation of ampk and glucose uptake in cultured human skeletal muscle cells from patients with me/cfs
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5938427/
https://www.ncbi.nlm.nih.gov/pubmed/29654166
http://dx.doi.org/10.1042/BSR20180242
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