Metformin mechanism of action in reducing blood glucose still elusive. Researchers found both of metformin's effect but which is more potent in treatment (uptake or production)
As far as I know, metformin is an inhibitor of oxidative phosphorylation thus causing an activation of AMPK.. In turn AMPK activation increases glucose uptake in muscle (glut4), while in the liver increases glycolysis, decrease gluconeogenesis and stimulate fatty acids degradation inhibiting ACC and therefore fatty acids synthesis. AMPK is connected with mTOR regulation pathway and also with sirtuins, therefore the pathways that can be altered upon metformin treatment are many and fundamental for cell metabolism differentiation and proliferation, Furthermore I am afraid that we know only the surface of the complex system regulating cellular mechanisms as function of energy supply, so is very hard to exactly determine the whole effects exerted by metformin.
Of course metformin inhibits mGPD and inhibits complex 1 enzyme (mitochondria) but in both cases the action still inside mitochondria (inhibition of mitochondrial function).
1- Inhibition of mitochondrial complex 1: activation of AMPK which result in increase glycolysis, decrease gluconeogenesis.
2- Inhibition of mGPD: this cause decrease in mitochondrial redox state increase and in cytosolic redox state. so plasma glycerol and lactate will increase and then gluconeogenesis inhibited.
In the first case increase glycolysis means increase glucose uptake.
In the second case: main consequences inhibition of gluconeogenesis (decrease glucose production).
we know the role of skeletal muscle and adipose tissues in GLUT4 and increase of glucose uptake because inhibition of cellular respiration. but I need to know about the liver because the pathogenesis of diabetes start from liver (accumulation of fats and increase in TG production).....
Activation of AMPK occures when high doses of metformin is used while inhibition of mGPD when low doses of the drug is used.