Voluntary exercise improves metabolic profile in high-fat fed glucocorticoid-treated rats

Diabetes is rapidly induced in young male Sprague-Dawley rats following treatment with exogenous corticosterone (CORT) and a high-fat diet (HFD). Regular exercise alleviates insulin insensitivity and improves pancreatic β-cell function in insulin-resistant/diabetic rodents, but its effect in an animal model of elevated glucocorticoids is unknown. We examined the effect of voluntary exercise (EX) on diabetes development in CORT-HFD-treated male Sprague-Dawley rats (∼6 wk old). Animals were acclimatized to running wheels for 2 wk, then given a HFD, either wax (placebo) or CORT pellets, and split into 4 groups: placebo-sedentary (SED) or -EX and CORT-SED or -EX. After 2 wk of running combined with treatment, CORT-EX animals had reduced visceral adiposity, and increased skeletal muscle type IIb/x fiber area, oxidative capacity, capillary-to-fiber ratio and insulin sensitivity compared with CORT-SED animals (all P < 0.05). Although CORT-EX animals still had fasting hyperglycemia, these values were significantly improved compared with CORT-SED animals (14.3 ± 1.6 vs. 18.8 ± 0.9 mM). In addition, acute in vivo insulin response to an oral glucose challenge was enhanced ∼2-fold in CORT-EX vs. CORT-SED (P < 0.05) which was further demonstrated ex vivo in isolated islets. We conclude that voluntary wheel running in rats improves, but does not fully normalize, the metabolic profile and skeletal muscle composition of animals administered CORT and HFD.