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

I’m not sure I actually count as a “proper expert”, but here goes:

That video was pretty detailed. But the principle of how AMPK operates is pretty simple. Its senses the energy state of the cell, and when the cell starts to run low on fuel AMPK responds by boosting energy production, and damping down energy consuming processes.

So as you say, if AMPK isn’t responding properly, that could cause a lot of problems.

AMPK is basically responding to a fall in ATP, which is the cell’s main fuel molecule. It actually senses the related molecule AMP rather than ATP - AMP levels rise as ATP levels fall.

Note, though, that while the study found that the drug treatments did increase AMPK activation, they didn’t actually boost cellular ATP levels.

 

If the underlying signalling mechanism is not identified then tweaking AMPK activation may cause more harm than good.

Would having low intracellular ATP not imply that its loss has triggered AMPK activation and CDR? Homeostasis at lowered rate will continue until ATP depletion is addressed.
When we did ATP profiles test , daughter' s cellular response was to be overefficient at chucking ATP into cytosol - far faster than ADP could be converted to ATP - was this signalling? Instigation of CDR response. Supply and demand had become uncoupled.

There is a very interesting thread on the other place trying to pull things together, looking at puringenic signalling . I looked at it last year, so probably developed a bit since.

Gets a bit complex for me but did seem to start to make sense of things. AMPK being part of the mix

http://forums.phoenixrising.me/inde...-in-pursuit-of-a-unified-me-cfs-theory.55801/

 

Dr Mark Guthridge of Monash University in Melbourne has given his thoughts on the possible use and results of giving Metformin to ME/CFS patients on Twitter.

They chime with reports on various forums given by Valentijn & others.

https://twitter.com/user/status/987935870236815360

 

https://twitter.com/user/status/987935873458057216

 

PS Mark Guthridge is definitely worth following on Twitter. He seems a knowledgeable communicative guy.

 

Never heard of Mark Guthridge, is he another M.E researcher? I love to hear new names on the case

 

When I took Metformin (doctor at that time was suspecting PCOS on top of everything else) my muscles simply packed up. I could barely move. Had a severe gut ache but the memory that remains was of being almost paralysed with weakness.

My post exertional ME is like that for me (the muscle weakness) but this was bringing on a severe form of it without the exertion.

 

I took it for a few years, for type 2 diabetes, without significant problems, a few side effects that were generally below the normal threshold of my ME symptoms. Then for no obvious reason significant levels of gastric issues started, yes I ended up very weak and unable to function but I would hesitate to say that was an effect of Metformin on my mitochondria, more the cumulative effect of spending several hours a day, every day, on the toilet in moderate to severe pain, had on my ME.

My understanding (from google searches) is that this is a known reaction and is surmised (by "healthy" T2Ds) to be the intended method of action, make people ill enough so they can't eat and blood glucose levels drop, weight drops, another checkbox ticked by the doctor, and thus 2 payouts to the GP (BG and weight loss).

Combined with ME, it's not much fun.

 

A close healthy friend of mine who is a top rated table tennis player did poorly on Metformin. It gave him muscle weakness and he could hardly compete because of depleted energy levels.