Endurance exercise training increases APPL1 expression and improves insulin signaling in the hepatic tissue of diet-induced obese mice, independently of weight loss

Hepatic insulin resistance is the major contributor to fasting hyperglycemia in type 2 diabetes. The protein kinase Akt plays a central role in the suppression of gluconeogenesis involving forkhead box O1 (Foxo1) and peroxisome proliferator-activated receptor gamma co-activator 1 alpha (PGC-1a), and in the control of glycogen synthesis involving the glycogen synthase kinase beta (GSK3 beta) in the liver. It has been demonstrated that endosomal adaptor protein APPL1 interacts with Akt and blocks the association of Akt with its endogenous inhibitor, tribbles-related protein 3 (TRB3), improving the action of insulin in the liver. Here, we demonstrated that chronic exercise increased the basal levels and insulin-induced Akt serine phosphorylation in the liver of diet-induced obese mice. Endurance training was able to increase APPL1 expression and the interaction between APPL1 and Akt. Conversely, training reduced both TRB3 expression and TRB3 and Akt association. The positive effects of exercise on insulin action are reinforced by our findings that showed that trained mice presented an increase in Foxo1 phosphorylation and Foxo1/PGC-1a association, which was accompanied by a reduction in gluconeogenic gene expressions (PEPCK and G6Pase). Finally, exercised animals demonstrated increased at basal and insulin-induced GSK3 beta phosphorylation levels and glycogen content at 24?h after the last session of exercise. Our findings demonstrate that exercise increases insulin action, at least in part, through the enhancement of APPL1 and the reduction of TRB3 expression in the liver of obese mice, independently of weight loss. J. Cell. Physiol. 227: 29172926, 2012. (C) 2011 Wiley Periodicals, Inc.

Lack of beta(2)-AR improves exercise capacity and skeletal muscle oxidative phenotype in mice

beta(2)-adrenergic receptor (beta(2)-AR) agonists have been used as ergogenics by athletes involved in training for strength and power in order to increase the muscle mass. Even though anabolic effects of beta(2)-AR activation are highly recognized, less is known about the impact of beta(2)-AR in endurance capacity. We presently used mice lacking beta(2)-AR [beta(2)-knockout (beta(2) KO)] to investigate the role of beta(2)-AR on exercise capacity and skeletal muscle metabolism and phenotype. beta(2) KO mice and their wild-type controls (WT) were studied. Exercise tolerance, skeletal muscle fiber typing, capillary-to-fiber ratio, citrate synthase activity and glycogen content were evaluated. When compared with WT, beta 2KO mice displayed increased exercise capacity (61%) associated with higher percentage of oxidative fibers (21% and 129% of increase in soleus and plantaris muscles, respectively) and capillarity (31% and 20% of increase in soleus and plantaris muscles, respectively). In addition, beta 2KO mice presented increased skeletal muscle citrate synthase activity (10%) and succinate dehydrogenase staining. Likewise, glycogen content (53%) and periodic acid-Schiff staining (glycogen staining) were also increased in beta 2KO skeletal muscle. Altogether, these data provide evidence that disruption of beta(2)AR improves oxidative metabolism in skeletal muscle of beta 2KO mice and this is associated with increased exercise capacity.

Similar health benefits of endurance and high-intensity interval training in obese children

Purpose: To compare two modalities of exercise training (i.e., Endurance Training [ET] and High-Intensity Interval Training [HIT]) on health-related parameters in obese children aged between 8 and 12 years. Methods: Thirty obese children were randomly allocated into either the ET or HIT group. The ET group performed a 30 to 60-minute continuous exercise at 80% of the peak heart rate (HR). The HIT group training performed 3 to 6 sets of 60-s sprint at 100% of the peak velocity interspersed by a 3-min active recovery period at 50% of the exercise velocity. HIT sessions last similar to 70% less than ET sessions. At baseline and after 12 weeks of intervention, aerobic fitness, body composition and metabolic parameters were assessed. Results: Both the absolute (ET: 26.0%; HIT: 19.0%) and the relative VO2 peak (ET: 13.1%; HIT: 14.6%) were significantly increased in both groups after the intervention. Additionally, the total time of exercise (ET: 19.5%; HIT: 16.4%) and the peak velocity during the maximal graded cardiorespiratory test (ET: 16.9%; HIT: 13.4%) were significantly improved across interventions. Insulinemia (ET: 29.4%; HIT: 30.5%) and HOMA-index (ET: 42.8%; HIT: 37.0%) were significantly lower for both groups at POST when compared to PRE. Body mass was significantly reduced in the HIT (2.6%), but not in the ET group (1.2%). A significant reduction in BMI was observed for both groups after the intervention (ET: 3.0%; HIT: 5.0%). The responsiveness analysis revealed a very similar pattern of the most responsive variables among groups. Conclusion: HIT and ET were equally effective in improving important health related parameters in obese youth.

Endurance training stimulates growth and survival pathways and the redox balance in rat pancreatic islets

Calegari VC, Abrantes JL, Silveira LR, Paula FM, Costa JM Jr, Rafacho A, Velloso LA, Carneiro EM, Bosqueiro JR, Boschero AC, Zoppi CC. Endurance training stimulates growth and survival pathways and the redox balance in rat pancreatic islets. J Appl Physiol 112: 711-718, 2012. First published December 15, 2011; doi:10.1152/japplphysiol.00318.2011.-Endurance training has been shown to increase pancreatic beta-cell function and mass. However, whether exercise modulates beta-cell growth and survival pathways signaling is not completely understood. This study investigated the effects of exercise on growth and apoptotic markers levels in rat pancreatic islets. Male Wistar rats were randomly assigned to 8-wk endurance training or to a sedentary control group. After that, pancreatic islets were isolated; gene expression and the total content and phosphorylation of several proteins related to growth and apoptotic pathways as well as the main antioxidant enzymes were determined by real-time polymerase chain reaction and Western blot analysis, respectively. Reactive oxygen species (ROS) production was measured by fluorescence. Endurance training increased the time to reach fatigue by 50%. Endurance training resulted in increased protein phosphorylation content of AKT (75%), AKT substrate (AS160; 100%), mTOR (60%), p70s6k (90%), and ERK1/2 (50%), compared with islets from control group. Catalase protein content was 50% higher, whereas ROS production was 49 and 77% lower in islets from trained rats under basal and stimulating glucose conditions, respectively. Bcl-2 mRNA and protein levels increased by 46 and 100%, respectively. Bax and cleaved caspase-3 protein contents were reduced by 25 and 50% in islets from trained rats, respectively. In conclusion, these results demonstrate that endurance training favors the beta-cell growth and survival by activating AKT and ERK1/2 pathways, enhancing antioxidant capacity, and reducing ROS production and apoptotic proteins content.

Isokinetic Strength and Endurance in Proximal and Distal Muscles in Patients With Peripheral Artery Disease

Background: The objective of this study was to analyze the muscle strength and endurance of the proximal and distal lower-extremity muscles in peripheral artery disease (PAD) patients. Methods: Twenty patients with bilateral PAD with symptoms of intermittent claudication and nine control subjects without PAD were included in the study, comprising 40 and 18 legs, respectively. All subjects performed an isokinetic muscle test to evaluate the muscle strength and endurance of the proximal (knee extension and knee flexion movements) and distal (plantar flexion and dorsiflexion movements) muscle groups in the lower extremity. Results: Compared with the control group, the PAD group presented lower muscle strength in knee flexion (-14.0%), dorsiflexion (-26.0%), and plantar flexion (-21.2%) movements (P < 0.05) but similar strength in knee extension movements (P > 0.05). The PAD patients presented a 13.5% lower knee flexion/extension strength ratio compared with the control subjects (P < 0.05), as well as lower muscle endurance in dorsiflexion (-28.1%) and plantar flexion (-17.0%) movements (P < 0.05). The muscle endurance in knee flexion and knee extension movements was similar between PAD patients and the control subjects (P > 0.05). Conclusion: PAD patients present lower proximal and distal muscle strength and lower distal muscle endurance than control patients. Therefore, interventions to improve muscle strength and endurance should be prescribed for PAD patients.

The effects of long-term endurance training on the immune and endocrine systems of elderly men: the role of cytokines and anabolic hormones

Abstract Background a decline in immune and endocrine function occurs with aging. The main purpose of this study was to investigate the impact of long-term endurance training on the immune and endocrine system of elderly men. The possible interaction between these systems was also analysed. Results elderly runners showed a significantly higher T cell proliferative response and IL-2 production than sedentary elderly controls. IL-2 production was similar to that in young adults. Their serum IL-6 levels were significantly lower than their sedentary peers. They also showed significantly lower IL-3 production in comparison to sedentary elderly subjects but similar to the youngs. Anabolic hormone levels did not differ between elderly groups and no clear correlation was found between hormones and cytokine levels. Conclusion highly conditioned elderly men seem to have relatively better preserved immune system than the sedentary elderly men. Long-term endurance training has the potential to decelerate the age-related decline in immune function but not the deterioration in endocrine function.