All animal experiments were performed according to procedures approved by Beth Israel Deaconess Medical Center’s Institutional Animal Care and Use Committee. The mice (strain: B6.Cg-Lepob/J from Jackson Labs) were 8 weeks old when administered inhibitor or vehicle by once daily oral gavage for 5 days. Doses in mice (GSK1120212, 3 mg/kg in DMSO; PD0325901, 10 mg/kg in DMSO) were diluted in 15% Cremophor EL/ 82% saline/ 3% drug or DMSO were comparable to that given in human clinical trials [5 (link), 9 (link), 10 (link), 14 (link)]. Kidneys, livers, and pancreata from nine mice were dissected and flash frozen in liquid nitrogen.