Combination of bofutsushosan (Kampo medicine) and voluntary exercise improves insulin sensitivity in Otsuka Long‐Evans Tokushima fatty rats

Aim Previous studies have shown that the traditional Kampo medicine bofutsushosan (BTS) has an anti-obesity effect. In the current study, we investigated the effects of BTS and voluntary exercise, and their combination on insulin sensitivity in Otsuka Long-Evans Tokushima fatty (OLETF) rats. Methods Male OLETF rats aged 16 weeks were divided into four groups: standard powdered diet (C); powdered diet containing BTS (BTS); access to a running wheel for voluntary running exercise and standard diet (EX); and combined BTS and EX (BTS + EX). After 7 weeks, euglycemic clamp (insulin infusion rate: 3.0 mU/kg/min) was performed in awake rats and the insulin-signaling pathway in skeletal muscle was evaluated. Results At 23 weeks of age, C, BTS, EX and BTS + EX rats showed an average of 656, 582, 459 and 417 g and had epididymal fat mass of 2.99, 2.36, 1.09 and 0.66 g/100 g bodyweight respectively. Glucose infusion rate (GIR) during euglycemic clamp was significantly higher in BTS and EX rats than in C rats. In addition, GIR in BTS + EX rats was significantly higher than in C, BTS and EX rats. The total content of skeletal muscle insulin receptor β-subunit and insulin receptor substrate-1 protein was significantly increased in EX and BTS + EX rats compared with C rats. Conclusion Combination of BTS and EX could be considered beneficial for the prevention and treatment of obesity-induced type 2 diabetes mellitus.