Steven
I was doing a bit of information gathering on AMPK activators, of which metformin is one, and came across information that metformin is an mTOR inhibitor and and autophagy inducer. The autophagy inducer information I found interesting. Any idea how potent this action is and whether it mitigates autophagy inhibition by chloroquine?
As you know, autophagy is complex, as it can either be a survival mechanism, or alternatively, lead to autophagic cell death. In an esophageal cancer model co-administration of metformin (intraperitoneally injected) with chloroquine was synergistic and inhibited tumor volume far more effectively than metformin alone.
ReplyDeletehttp://www.nature.com/cddis/journal/v5/n2/full/cddis201459a.html#Results
http://www.nature.com/cddis/journal/v5/n2/extref/cddis201459x5.jpg
However, these ip injections of high dose metformin lead to plasma levels far higher than humans get with typical diabetic doses. I have a hard time believing metformin has much direct effect on glioma cells in the brain, and I focus more on the potential systemic effects (on circulating glucose, insulin, IGF-1, and immune effects).