Oliver's mTOR Atlas Evidence Platform
Reading level
Mode

Pathway link METFORMIN-MTORC1

Metformin mTORC1

Metformin inhibits mTORC1.

Metformin can also block mTORC1 through a separate route that doesn't need AMPK – a route often left out of the simple "metformin works via AMPK" story. This was shown in cells and mice, often at doses higher than patients take, and how much each route matters in people is not known.

Metformin also inhibits mTORC1 WITHOUT going through AMPK: the effect survives in AMPK-null and TSC1/2-null cells and instead requires the Rag GTPases. This is the arm usually left out of the 'metformin works via AMPK' summary.

The conditions it holds under

Runs in parallel with METFORMIN-AMPK, not instead of it. The relative weight of the two routes in humans is unresolved.

Dose is the whole argument. Concentrations used in cell culture are typically far above plasma levels achieved at clinical doses, so in vitro mechanism may not describe what metformin does in a patient.

Time it takes
hours
Step
indirect (through steps not drawn here)
Measured in
mammalian cells, mouse liver
Where in the cell
cytosol
Reaches people?
plausible in people, not shown directly
How settled
disputed: at least one study points the other way

Studies behind it

YearEvidenceStudy
2010 M Metformin, independent of AMPK, inhibits mTORC1 in a rag GTPase-dependent mannerKAL2010 Metformin inhibits mTORC1 even in cells lacking AMPK or TSC1/TSC2, and the effect requires the Rag GTPases instead. Together with Foretz 2010 this places a large part of metformin's action outside the AMPK axis it is usually credited to.

Points the other way

No study in the Atlas contradicts this link. That means none in this curated set, not none in the literature.

Who has checked this

Checked by
No researcher outside the project has checked this link yet.
Curator sign-off
Not signed off yet. This link was drafted with AI help and has not been reviewed link by link; treat it as a proposal until it is.
Curated by
Oliver Barton, with AI help for drafting; see how links are checked.

“Inhibits” describes the effect on the target's activity, not on how much of it there is.

“How settled” describes how far researchers in the field agree. It is not the same as the sign-off above, which only says whether a named curator has checked this page.

If this link rests on your own work: a click on “This looks right” below, or a short note through “Report an error”, helps us more than anything else on this page.

← The whole pathway · This link as JSON

Was this page useful?
Spotted something wrong or out of date about this link?