Protective effect of W2476 on DIO mice. Four-week-old male C57BL/6 mice were fed on SCD or HFD for 4 weeks. At approximately 8 weeks of age, they were treated with W2476 (200 or 400 mg·kg−1·d−1), verapamil (100 mg·kg−1·d−1) or vehicle for 6 weeks (n=11–12 per group). (A, B) Body weight on the last day of dosing and the average food intake during the 6-week treatment period. (C) The 6-h fasting blood glucose levels at weeks 0, 3 and 6. (D, E) Effects of W2476 and verapamil on pancreatic TXNIP protein levels in each group. At the end of treatment, plasma insulin levels were examined (F), and ITT was carried out to measure blood glucose response (G) and associated AUC0–120(H) in each group. Data shown are mean±SEM. *P<0.05, **P<0.01 vs SCD group. #P<0.05, ##P<0.01 vs HFD group.