We investigated the role of insulin receptor substrate (Irs)-1 for diethylnitrosamine (DEN) plus high-fat (HF) diet-induced hepatic tumorigenesis in mice. We gave DEN by intraperitoneal injection at the dose of 80 mg/kg to 18-week-old wild-type (WT) and Irs1-knockout (Irs1-/-) mice, which were fed a HF diet from 8 weeks-of-age until they were killed (52 weeks). The Irs1-/- mice showed significa…