Fig. 1.
Complementation analysis demonstrates a selective role for hepatic JNK2α in the regulation of glycemia. (A) Primary hepatocytes prepared from wild-type (WT) mice (Alb-Cre−/+ Mapk8+/+ Mapk9+/+), knockout (KO) mice with hepatocyte-specific JNK1 plus JNK2 KO (Alb-Cre−/+ Mapk8loxP/loxP Mapk9loxP/loxP), and KO mice complemented with AAV-mediated expression of JNK2α or JNK2β were treated with 1 µg/mL anisomycin (Aniso) (15 min). Lysates were examined by immunoblot analysis by probing with antibodies to pSer63 JUN (pJUN), JUN, JNK, and α-tubulin. (B and C) Blood FGF21 and glucose concentration in HFD-fed mice (16 wk) expressing JNK2α or JNK2β in hepatocytes was measured (mean ± SEM; *P < 0.05, ***P < 0.001; n = 6∼8). (D and E) GTTs and PTTs on HFD-fed mice (16 wk) expressing JNK2α or JNK2β in hepatocytes were performed and the area under the curve (AUC) was measured (mean ± SEM; **P < 0.01, ***P < 0.001; n = 6∼8).