Pharmacological activation of AMPK and glucose uptake in cultured human skeletal muscle cells from patients with ME/CFS (2018) Newton et al

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hixxy

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

Brown AE, Dibnah B, Fisher E, Newton JL, Walker M.

Abstract

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 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.

KEYWORDS:
AMPK; glucose uptake; muscle contraction
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https://www.ncbi.nlm.nih.gov/pubmed/29654166
 
I have no idea what AMPK is or does. I googled and found this incredibly complicated diagram. My head exploded.

https://media.cellsignal.com/www/pdfs/science/pathways/AMPK.pdf

This was a little more helpful:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3249400/
''The AMP-activated protein kinase (AMPK) signaling pathway coordinates cell growth, autophagy, & metabolism'' (2011)
Here's part of the abstract:
One of the central regulators of cellular and organismal metabolism in eukaryotes is the AMP-activated protein kinase (AMPK), which is activated when intracellular ATP levels lower. AMPK plays critical roles in regulating growth and reprogramming metabolism, and recently has been connected to cellular processes including autophagy and cell polarity.
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Amw66 said:
From the other place - a few threads
AMPK in blood cell deformity
http://forums.phoenixrising.me/inde...ormability-in-me-cfs.58380/page-2#post-966242
AMPK role in M3 signalling
http://forums.phoenixrising.me/inde...e-treatment-for-cfs.37244/page-94#post-959851
AMPK in purinergic signalling
http://forums.phoenixrising.me/inde...nified-me-cfs-theory.55801/page-5#post-932764
AMPK and Metformin
http://forums.phoenixrising.me/inde...prof-ron-davis-video.56737/page-3#post-943184
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There's also a thread from AndyPandy who talks about their experiences withMetformin as a type 2 diabetic. They may be very different from people without Type 2 diabetes.

ME and Metformin

http://forums.phoenixrising.me/index.php?threads/me-and-metformin.47425/
 
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From the discussion

"The important findings from this study are that, firstly, pharmacological activation of AMPK can improve glucose uptake in skeletal muscle cell cultures from patients with ME/CFS and secondly, cellular ATP content is significantly reduced in ME/CFS muscle cell cultures.

The observation that AMPK was activated directly by metformin and 991 but not EPS (electrical pulse stimulation) in the ME/CFS cultures points to a signalling defect proximal to AMPK"
 
Like @Trish, I've been trying to understand AMPK signalling without causing instant brain fog. Found this video on YouTube, which has enlightened me slightly.

Out of many things AMPK does, it instructs cells to take in more glucose to make more ATP and to store less glucose as glycogen (in the liver) when the ratio of ATP drops.

You can see the point if the AMPK signalling is messed up, it could cause energy shortages. (my non bio-chemist take)

I'll shut up now & let the proper experts correct me and take over. @Simon M is a proper biochemist not a 5 minute one :)

 
I found some AMPK activators for a blog post 3 years ago



I’ve been thinking about my very fluctuating ME journey over the last 20 years. I’ve been around 10% and around 95% on the Bell Disability Scale and everything in between up and down at different times. This week I’ve been thinking about when I went from 10% to 30% in a couple of weeks (with the help of a nutritionist). It could be a number of things but I started this supplement (Fast & be clear) at that point

FB7496_FC_5981_4_AE2_9_F5_A_9_C3458_D0_E583.png


My understanding is Quercetin, alpha lipoic acid, grapes and green tea are AMPK activators. I wonder if this was part of the benefit of taking this supplement?
http://ampkactivator.net/quercetin/
http://ampkactivator.net/a-lipoic-acid/
 
Estherbot said:
From the discussion

"The important findings from this study are that, firstly, pharmacological activation of AMPK can improve glucose uptake in skeletal muscle cell cultures from patients with ME/CFS and secondly, cellular ATP content is significantly reduced in ME/CFS muscle cell cultures.

The observation that AMPK was activated directly by metformin and 991 but not EPS (electrical pulse stimulation) in the ME/CFS cultures points to a signalling defect proximal to AMPK"
Click to expand...
Cellular ATP content bring low is what Myhill, Booth et al found, together with low cellular magnesium bound ATP ( not active without Mg)
 
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