GeneChips. The mRNA was isolated from the livers of overnight-fasted WT, fIrs2, LKO, Irs1^–/–, and LKO::Irs1^–/– mice (2 mice per genotype). Each sample was labeled and analyzed on Affymetrix Mouse Genome 430 2.0 GeneChips at the Harvard Medical School Biopolymers Facility. ANOVA without a multiple testing correction identified 1,414 probe sets that changed significantly (P < 0.05) across all of the groups, and a 1-sample Student’s t test was used to determine whether the mean normalized expression value for each of the 1,414 probes was statistically different from the WT control. (A–D) The P value for each probe set was plotted against its fold change (Δ) fIrs2, LKO::Irs1^–/–, Irs1^–/–, and LKO. Probe sets falling outside the gray zone (P < 0.05 and at least a 2-fold change) are listed in Table 1. (E) Real-time PCR was used to estimate the expression of several candidate genes known to play a role in hepatic glucose homeostasis — Pck1, Glut2, G6pc, Gck, and Ppargc1 — or lipid homeostasis — Pparg, Srebp1, Acc1, Fasn, carnitine palmitoyltransferase 1a (Cpt1a), and Hmgcs1. Data represent the average of replicate determinations from fasted mouse liver extracts normalized against 18S. Expression relative to the fIrs2 liver is presented by log 2 (fold change). *P < 0.05 (ANOVA).