Stress-activated systems and oxidative stress are involved in
insulin resistance, which, along with beta-cell failure, contribute to the development of
type 2 diabetes mellitus (T2DM). Exercise improves
insulin resistance and
glucose tolerance, and these adaptations may, in part, be related to reductions in
inflammation and oxidative stress. We investigated circulating and tissue-specific markers of
inflammation and oxidative stress and
insulin-signaling pathways in a rodent model of T2DM, the Zucker diabetic fatty rat, with and without voluntary exercise. At 5 wk of age, Zucker diabetic fatty rats (n = 8-9/group) were divided into basal (B), voluntary exercise (E), and sedentary control (S) groups. B rats were euthanized at 6 wk of age, and S and E rats were euthanized 10 wk later. E rats ran approximately 5 km/day, which improved
insulin sensitivity and maintained fed and fasted
glucose levels and
glucose tolerance. Ten weeks of exercise also decreased whole body markers of
inflammation and oxidative stress in plasma and liver, including lowered circulating
IL-6,
haptoglobin, and
malondialdehyde levels, hepatic
protein oxidation, and phosphorylated JNK, the latter indicating decreased JNK activity. Hepatic
phosphoenolpyruvate carboxykinase levels and Ser(307)-phosphorylated
insulin receptor substrate-1 were also reduced in E compared with S rats. In summary, we show that, in a rodent model of T2DM, voluntary exercise decreases circulating markers of
inflammation and oxidative stress and lowers hepatic JNK activation and Ser(307)-phosphorylated
insulin receptor substrate-1. These changes in oxidative stress markers and
inflammation are associated with decreased
hyperglycemia and
insulin resistance and reduced expression of the main gluconeogenic
enzyme phosphoenolpyruvate carboxykinase.