NeuroTalk Support Groups - So which "existing" diabetes drug turns the PGC-1 Alpha "Master Switch" back on?

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- - So which "existing" diabetes drug turns the PGC-1 Alpha "Master Switch" back on? (https://www.neurotalk.org/parkinson-s-disease/134572-existing-diabetes-drug-pgc-1-alpha-master-switch.html)

Those following this subject might find this of interest.
http://onlinelibrary.wiley.com/doi/1...10.00090.x/pdf

Quote:

Yep, that's why I wondered whether this was just old but updated news which essentially it is. Researchers were onto this four years go, but I guess the genetic link and the master switch thing are the key new developments.
The brand name is Actos. I guess this is one of the few that doesn't have nasty cardiac side effects. There is a really great article in Nature on all of this. You'll love this quote:
... a clinical trial to test Actos in patients with Parkinson's disease has already been approved by regulators.
No trial to date that I can find at clinicaltrials.gov

Thanks for including the "Nature" article.
If I was reading it correctly, the regulators, referred to in the article, are in Europe. So perhaps there is a trial going on there.
I am definitely going to look into Actos after seeing the Science Daily article today on research from Harvard.

PGC-1 activation causes severe side effects

It would be important to realize that activation of PGC-1 {alpha} and {beta} has severe side effects that can occur during a treatment:

Below a summary about the possible problems:
- When PGC-1 {alpha} or {beta} are higher in the muscle, tumor necrosis factor {alpha} (TNF {alpha}) is elevated. More TNF {alpha}, a mediator of inflammation, is secreted into the blood (cf. Olesen J et al; Medicine & Science in Sports & Exercise: October 2010 - Volume 42 - Issue 10 - p 58.
- The same article shows this at basal levels and that it worsens following injection of TNF into muscle.
- When PGC-1 is elevated more lipids are accumulating in muscle. People can become obese. Lipids often induce inflammation (cf. Summermatter S et al; Journal of biological chemistry: October 2010 22;285(43):32793-800)
- Then PGC-1 can even induce diabetes when too high (cf. Miura S, Journal of biological chemistry: August 2003 15;278(33):31385-90.)
- High PGC-1 {alpha} and {beta} levels, basal and after stimulation by TNF or Lipopolysaccharide (LPS) lead to high expression and release of inflammatory IL (interleukin) and of macrophage infiltration as indicated by CD (cluster of differentiation)

All this should be kept in mind. Maybe it's still ok to develop drugs that promote PGC-1, but it should be considered that this can have these side effects.