History
Metformin has a deep and incredible history in the treatment of diabetes. In ancient Europe, it was used as a folk medicine from a plant known as Galega officinalis, as its anti diabetic properties were seen. In the 1920's, the drug was synthesized into a more safer form and the popularity of the drug has grown (He et al, 2015). It is very common in fighting type II diabetes and 150 million people depend on the drug (He et al, 2015).
Figure 3: The Galega officinalis plant
Many theories exist on how metformin works. It inhibits gluconeogenesis, however, it is not known how it does this.
Theories
AMPK
Through AMPK and turning off genes, metformin inhibits gluconeogenesis (Zhou et al).
Enzymes in Gluconeogenesis
Through inhibiting the direct enzymes required for gluconeogenesis, metformin inhibits gluconeogenesis. (Madiraju et al, 2014)
AMPK
Through AMPK and turning off genes, metformin inhibits gluconeogenesis (Zhou et al).
Enzymes in Gluconeogenesis
Through inhibiting the direct enzymes required for gluconeogenesis, metformin inhibits gluconeogenesis. (Madiraju et al, 2014)
Figure 4: LKB1/AMPK Pathway
Does metformin inhibit the pyruvate carboxylase enzyme? Possibly... around 250 to 500 micromolar?
Figure 5: Pyruvate Carboxylase being inhibited, leads to lower glucose output.
Pyruvate Carboxylase
Inhibition of pyruvate carboxylase will lead to inhibition of pyruvate carboxylase, however, it can only work through a molecule called biotin (Attwood, 1995).
Pyruvate Carboxylase
Inhibition of pyruvate carboxylase will lead to inhibition of pyruvate carboxylase, however, it can only work through a molecule called biotin (Attwood, 1995).