Figure 4.

Impact of Insr genotype on hepatic glucose fluxes and gene expression. (A) The rates of endogenous GP and of G6Pase flux were markedly increased in L1 (white bars) compared with WT (black bars) mice. (B) The rate of gluconeogenesis (GNG) was markedly increased in L1 compared with WT mice, while the rate of glycogenolysis (GLG) was not significantly changed. (C) The rate of glucose cycling (GC) was also markedly increased in L1 compared with WT mice. (D) The hepatic expressions of insulin-responsive genes such as PEPCK, G6Pase, and IGFBP1 were not affected in L1 mice. (E) In summary, in the presence of physiological hyperinsulinemia, L1 mice displayed a dramatic increase in the rate of gluconeogenesis (indicated by the thicker arrows) that largely accounts for the increase in glucose output. GK, glucokinase; G6-P, glucose-6-phosphate; UDP-G, UDP-glucose. The values represent mean ± SEM.