Effect of CNX-010-49 on insulin sensitivity, hyperinsulinemia and glucose clearance in DIO mice on HFD. At the end of the treatment period, fasting and fed insulin levels (A) and OGTT was performed (B) by oral administration of glucose (2 g/kg); plasma glucose was measured and AUC was calculated. Data in all panels are mean ± SEM (n = 8/group). At the end of the treatment, adipose and muscle tissue samples were collected from Lean control (1), HFD Control (2) and CNX-010-49 treated animals (3) and subjected to Western blots for p-JNK/total JNK (C) for muscle and p-EIF2α/Actin (D) for adipose. The blots are representative date from five animals from each group. ITT (E) was performed in mice to determine the effect of CNX-010-49 on glucose clearance as mentioned in the Methods. mRNA expression levels of muscle PDK4 and TRIM63 (F & G) were measured as mentioned in Methods. Statistical comparison between control was conducted by One-way ANOVA followed by Dunnett’s test (n = 8 mice/group) (# - significance of HFD control against lean control, *- significance of CNX-010-49 treatment against HFD control) (*P < 0.05, **P < 0.01 and ***P < 0.001).