File:Ijms-23-14163-g001-550.webp

English: Figure 1. Mechanism deciphering the role of metformin in glucagon signaling. (1) Metformin acts by suppressing glucagon signaling, leading to decreased cAMP production in hepatocytes and lower glucagon-dependent glucose output from hepatocytes. Reduced cAMP synthesis lowers the activity of gluconeogenic gene phosphorylation regulators cAMP responsive element binding protein 1 (CREB1) and triiodide (I3PR). (2) ATP reduction lowers gluconeogenesis and increases AMP levels, which inhibits the key gluconeogenic enzyme fructose-bisphosphatase 1 (FBP1). (3) The acetyl-CoA carboxylase (ACC) was phosphorylated and inhibited malonyl-CoA and acyl-CoA synthesis, increasing acyl-CoA content entering mitochondria and leading to the oxidation of fatty acid.