Importance of AMPK in metformin suppression of liver glucose production

Metformin is now the most widely prescribed oral anti-diabetic agent worldwide, taken by over 150 million people annually. Although metformin has been used clinically to treat type 2 diabetes for over 60 years. Its mechanism of action remains only partially understood and controversial. In particular, this includes whether AMPK plays a role in metformin suppression of liver glucose production. To address this issue, we knocked out the AMPK catalytic alpha1 and alpha 2 subunits in the liver of HFD-fed adult homozygous mice. These mice were treated with a physiological relevent metformin dose (50 mg/kg/day) for 3 weeks. Liver samples were collected. 6 weeks old male floxed homozygous AMPK alpha1/2 mice were fed an HFD for 4 weeks, AAV8-TBG-E.V. and AAV8-TBG-Cre (1X10^11GC/mouse) were injected via jugular vein, and mice were treated with metformin (50 mg/kg/day) for 3 weeks, liver samples were collected after 16 h fast. There are 14 samples, 6 samples from control group (WT), another 8 samples from treated group (Cre KO).