E3 PreliminaryPreliminaryPEM requiredMechanisticPeer-reviewedReviewed
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 et al. · Bioscience reports · 2018 · DOI
Quick Summary
This study looked at muscle cells from ME/CFS patients to understand why their muscles struggle to use energy properly. Researchers tested two drugs (metformin and compound 991) that can activate AMPK, a protein that helps cells use glucose for energy. Both drugs successfully improved how the muscle cells used glucose, suggesting that the problem in ME/CFS muscles is not AMPK itself, but something that happens before AMPK gets activated.
Why It Matters
Understanding the specific molecular dysfunction in ME/CFS muscle metabolism is crucial for developing targeted treatments. This research identifies AMPK as a potential therapeutic target and narrows down where the metabolic defect originates, potentially opening pathways for drug development to improve muscle energy utilization and reduce fatigue in patients.
Observed Findings
- Both metformin and compound 991 significantly increased AMPK activation in ME/CFS muscle cell cultures
- Both drugs significantly increased glucose uptake in ME/CFS muscle cells
- ATP content was significantly lower in ME/CFS muscle cells compared to controls
- Pharmacological AMPK activation did not restore ATP content to normal levels in ME/CFS cells
- Healthy control muscle cells also responded to AMPK activators with improved glucose uptake
Inferred Conclusions
- AMPK itself is pharmacologically actionable and not inherently defective in ME/CFS muscle
- The failure of electrical pulse stimulation to activate AMPK in ME/CFS is due to a proximal signaling defect upstream of AMPK
- Pharmacological AMPK activation cannot compensate for reduced ATP production in ME/CFS muscle cells
- Further research is needed to identify the specific upstream molecular defect in the ME/CFS muscle signaling pathway
Remaining Questions
- What is the specific upstream molecular defect that prevents normal AMPK activation during muscle contraction in ME/CFS?
- Would AMPK activators improve muscle function and fatigue symptoms in living ME/CFS patients despite not restoring ATP levels in vitro?
What This Study Does Not Prove
This study does not prove that AMPK activators will improve symptoms in ME/CFS patients—these results are from laboratory-grown muscle cells, not whole living patients. It also does not identify the upstream defect causing AMPK activation failure during normal muscle contraction, nor does it demonstrate whether pharmacological AMPK activation would restore normal ATP production or muscle function in vivo.
Tags
Symptom:Post-Exertional MalaiseFatigue
Biomarker:MetabolomicsBlood BiomarkerGene Expression
Method Flag:Weak Case DefinitionSmall SampleExploratory Only
Metadata
- DOI
- 10.1042/BSR20180242
- PMID
- 29654166
- Review status
- Editor reviewed
- Evidence level
- Early hypothesis, preprint, editorial, or weak support
- Last updated
- 12 April 2026
About the PEM badge: “PEM required” means post-exertional malaise was an explicit required diagnostic criterion for participant inclusion in this study — not that PEM was studied, observed, or discussed. Studies using criteria that do not require PEM (e.g. Fukuda, Oxford) are tagged “PEM not required”. How the atlas works →
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