Exercise maintains euglycemia in association with decreased activation of c-Jun NH₂-terminal kinase and serine phosphorylation of IRS-1 in the liver of ZDF rats

Abstract

. Exercise maintains euglycemia in association with decreased activation of c-Jun NH2-terminal kinase and serine phosphorylation of IRS-1 in the liver of ZDF rats. Am J Physiol Endocrinol Metab 298: E671-E682, 2010. First published December 8, 2009 doi:10.1152/ajpendo.90575.2008.-Stress-activated systems and oxidative stress are involved in insulin resistance, which, along with ␤-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 ϭ 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 ϳ5 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.

Voluntary running exercise prevents β-cell failure in susceptible islets of the Zucker diabetic fatty rat

“…All but two exercise studies (23,44) in male ZDF rats have used forced treadmill running or swimming. During forced exercise, often conducted during the lights-on cycle, animals experience severe psychological stress and disruption of the normal circadian rhythm of the hypothalamic-pituitaryadrenal (HPA) axis (12).…”

“…The aim of the present study was to investigate the biochemical basis of the effects of physical activity on islet function in ZDF rats in which diabetes is prevented by voluntary running in wheel cages (23,44). Particular focus was placed on whether preserved ␤-cell performance in exercised ZDF rats could be linked to the compensatory pathway of enhanced GL/FA cycling similar to what was observed in compensating islets of ZF rats.…”

Effect of aging on islet beta-cell function and its mechanisms in Wistar rats

“…However, the mechanisms underlying the age-related decline in β-cell glucose-stimulated insulin release (GSIR) are unknown. Previous studies have suggested that oxidative stress-related β-cell apoptosis and the inhibition of proliferation are associated with β-cell dysfunction and the development of T2DM (Kiraly et al 2010;Harmon et al 2009). Recent studies have shown a reduction in β-cell proliferation and increased sensitivity to apoptosis triggers in elderly individuals (Rankin and Kushner 2009;Maedler et al 2006;Tschen et al 2009;Krishnamurthy et al 2006).…”

Odyssey between Scylla and Charybdis through storms of carbohydrate metabolism and diabetes: a career retrospective

“…During volitional exercise, in association with improvement in glycemia, we also observed decreased circulating markers of inflammation and oxidative stress [circulating IL-6, haptoglobin, MDA levels, and hepatic protein oxidation, phosporylated JNK (pJNK)]. Ser 307 -phosphorylated IRS-1 and PEPCK were also reduced in the liver of exercised rats (103). During each bout of exercise, plasma corticosterone increased, but, due to adaptation, basal cortisone is decreased.…”