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

Abstract

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.