c-Jun regulates gluconeogenesis in vivo and in vitro. (A) c-Jun mRNA and protein levels in the liver of c-jun△li mice. (B) Blood glucose levels. (C) glucose tolerance tests (GTTs). (D) pyruvate tolerance tests (PTTs). (E) insulin tolerance tests (ITTs). (F) Serum insulin levels. (G) HOMA-IR index. (H, I) Liver glycogen content under fed and fasting state. (J, K) Glucose output. Primary mouse hepatocytes were transfected with or without c-Jun siRNA for 48 h, or with or without c-Jun over-expressing plasmids for 24 h, and then treated with or without 100 nM glucagon for 10 h, followed by the measurement of glucose production. Data were obtained with mice indicated (n = 6–10 mice per group, 10–12 weeks old) or at least three independent in vitro experiments and presented as means ± SEMs. Statistical significance was calculated using two-tailed student t-test for the effects of c-jun△li mice versus control mice (*: p < 0.05) in A-I or one-way ANOVA followed by the Student-Newman-Keuls (SNK) test in J and K (*: p < 0.05 for the effects of any group versus the control group without glucagon stimulation, #: p < 0.05 c-Jun knockdown or over-expression group versus control group after glucagon stimulation).