Pathway link METFORMIN-AMPK
Metformin AMPK
Metformin activates AMPK.
Metformin shifts the cell's energy balance and switches AMPK on – its best-known route to affecting this pathway.
The conditions it holds under
How much of metformin's effect actually runs through AMPK is disputed: it still suppresses hepatic gluconeogenesis in AMPK-null and LKB1-null mouse liver (FOR2010) and still inhibits mTORC1 in AMPK-null cells (KAL2010). See the parallel METFORMIN-MTORC1 edge.
- Time it takes
- minutes
- Step
- indirect (through steps not drawn here)
- Measured in
- mammalian cells
- 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
| Year | Evidence | Study |
|---|---|---|
| 2001 | M | Role of AMP-activated protein kinase in mechanism of metformin actionZHO2001 Metformin activates AMPK, suppressing hepatic gluconeogenesis and lipogenesis. |
| 2009 | A | Enhancing CD8 T-cell memory by modulating fatty acid metabolismPEA2009 Mice whose T cells lacked the adaptor protein TRAF6 mounted a normal effector CD8 T-cell response to Listeria infection, but the antigen-specific cells vanished during contraction and almost no memory cells formed. The TRAF6-deficient cells failed to activate AMPK and mitochondrial fatty acid oxidation when the growth factor IL-2 was withdrawn. Daily metformin restored fatty acid oxidation and memory formation, and also raised memory CD8 T-cell numbers in normal mice: in a tumour vaccine model 6 of 9 metformin-treated mice survived beyond day 33 against 1 of 8 controls. Daily rapamycin (1.5 mg/kg), used as a second drug that promotes fatty acid oxidation, likewise increased memory CD8 T-cell development and recall responses. Boundary: mouse only, one bacterial infection model and one transplantable tumour; the rapamycin arm is a secondary experiment and mTOR activity itself was not measured in these cells. |
Points the other way
| Year | Evidence | Study |
|---|---|---|
| 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. |
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.
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