Exercise training improves basal blood glucose metabolism with no changes of cytosolic inhibitor κB kinase or c-Jun N-terminal kinase activation in skeletal muscle of Otsuka Long-Evans Tokushima fatty rats

Abstract

Redox-sensitive stress kinases and heat shock protein 72 (Hsp72) have been considered to be associated with the development of type 2 diabetes in skeletal muscle. However, the effect of exercise training on skeletal muscle of type 2 diabetic models is largely unknown. The purpose of this study was to investigate the effect of 12 weeks of exercise training on gastrocnemius of type 2 diabetic rats, by examining the activation of c-Jun N-terminal kinase (JNK), the nuclear factor B (NF-B) pathway and Hsp72. Total hydroperoxide and 4-hydroxynoneal, as oxidative stress markers, were also examined. Otsuka Long-Evans Tokushima fatty (OLEFT) rats were randomly divided into an exercise training group (Ex-OLETF, n = 8) and a sedentary group (Sed-OLETF, n = 8), while Long-Evans Tokushima Otsuka (LETO) rats were used as a control group (Con-LETO, n = 5). The Ex-OLETF rats were trained on a treadmill five times a week for 12 weeks. The levels of hydroperoxide and 4-hydroxynoneal in both Ex-OLETF and Sed-OLETF were significantly higher compared with Con-LETO, but there was no difference between Ex-OLETF and Sed-OLETF. Levels of inhibitor B kinase, JNK activation and p65 nuclear translocation followed a similar pattern to that observed in oxidative stress markers. The level of Hsp72 in Ex-OLETF was increased by exercise training, but it did not reach the level observed in Con-LETO. The NF-B DNA binding activity in Sed-OLETF was significantly higher compared with Con-LETO. Although it was not statistically significant, exercise training in Ex-OLETF showed a trend to reduce the activation of NF-B DNA binding activity compared with Sed-OLETF (P = 0.104). Our findings indicate that exercise training improves basal glucose metabolism without a change in stress kinases, and that nuclear regulation of NF-B activity in diabetic muscle could be regulated independently of the cytosolic pathway. Our study also suggests a possibility that exercise-induced Hsp72 serves as a protective mechanism in skeletal muscle of OLETF rats.