Figure 3. Mice with JNK1-deficient hepatocytes exhibit hepatic insulin resistance.

(A-F) Insulin sensitivity was measured using a hyperinsulinemic-euglycemic clamp in conscious chow-fed L^KO and L^WT mice. (A) Basal hepatic glucose production (HGP). (B) Insulin-stimulated rate of HGP. (C) Hepatic insulin action, expressed as insulin-mediated percent suppression of basal HGP. (D) Insulin-stimulated whole body glucose turnover. (E) Whole body fat mass measured using ¹H-MRS. (F) Whole body lean mass. The data presented are the mean ± SE for 6 ~ 8 experiments. Statistically significant differences between L^KO mice and L^WT mice are indicated (*, P < 0.05). (G,H) Chow-fed L^KO and L^WT mice were administered insulin (0.3U/kg body mass) by intravenous injection (5 mins). The activation of AKT in the liver was examined by immunoblot analysis by probing with antibodies to AKT and phosphoAKT. The relative amount of phosphoAKT is presented as the mean ± SD (n = 3). Statistically significant differences between L^KO and L^WT mice are indicated (*, P < 0.05). (I) Chow-fed L^KO and L^WT mice were administered insulin (0.3U/kg body mass) by intravenous injection (5 mins). The phosphorylation of IRS1 on Ser-307 in the liver was examined by immunoblot analysis by probing with antibodies to IRS1 and phosphoSer-307 IRS1.