Figure 1. Metformin suppresses hepatic mTORC1 signaling in an AMPK-dependent manner.

(A) Male mice (age 10 weeks) were fasted overnight then left unfed (Fast; n=2) or refed for 6 h, with saline, 200 or 250 mg/kg metformin treatment (n=3 per treatment) for the last 1 h. See Figure S1 for measurements of plasma metformin concentrations.

(B) Female AMPKα1^fl/fl/α2^fl/fl or L-AMPKα1/α2-DKO mice (age 6 mos) were fasted overnight, refed for 2 h and treated with saline or 250 mg/kg metformin for the last 1 h (n=4 per treatment). See Figure S1 for supporting data with a male cohort age 12 weeks.

(C,D) Primary hepatocytes were treated (C) for 5 h with indicated doses of metformin or 20 nM rapamycin (Rap) or (D) with 0.5 mM metformin for the indicated times.

(E) Primary hepatocytes from AMPKα1^fl/fl/α2^fl/fl or L-AMPKα1/α2-DKO mice were treated with the indicated concentrations of metformin for 2 or 5 h.