Exercise and Glycemic Control: Focus on Redox Homeostasis and Redox-Sensitive Protein Signaling

Physical inactivity, excess energy consumption, and obesity are associated with elevated systemic oxidative stress and the sustained activation of redox-sensitive stress-activated protein kinase (SAPK) and mitogen-activated protein kinase signaling pathways. Sustained SAPK activation leads to aberrant insulin signaling, impaired glycemic control, and the development and progression of cardiometabolic disease. Paradoxically, acute exercise transiently increases oxidative stress and SAPK signaling, yet postexercise glycemic control and skeletal muscle function are enhanced. Furthermore, regular exercise leads to the upregulation of antioxidant defense, which likely assists in the mitigation of chronic oxidative stress-associated disease. In this review, we explore the complex spatiotemporal interplay between exercise, oxidative stress, and glycemic control, and highlight exercise-induced reactive oxygen species and redox-sensitive protein signaling as important regulators of glucose homeostasis

Exercise and glycemic control: focus on redox homeostasis and redox-sensitive protein signaling

Physical inactivity, excess energy consumption, and obesity are associated with elevated systemic oxidative stress and the sustained activation of redox-sensitive stress-activated protein kinase (SAPK) and mitogen-activated protein kinase signaling pathways. Sustained SAPK activation leads to aberrant insulin signaling, impaired glycemic control, and the development and progression of cardiometabolic disease. Paradoxically, acute exercise transiently increases oxidative stress and SAPK signaling, yet postexercise glycemic control and skeletal muscle function are enhanced. Furthermore, regular exercise leads to the upregulation of antioxidant defense, which likely assists in the mitigation of chronic oxidative stress-associated disease. In this review, we explore the complex spatiotemporal interplay between exercise, oxidative stress, and glycemic control, and highlight exercise-induced reactive oxygen species and redox-sensitive protein signaling as important regulators of glucose homeostasis.<br /

What doesn’t kill you makes you fitter: A systematic review of high-intensity interval exercise for patients with cardiovascular and metabolic diseases

High-intensity interval exercise (HIIE) has gained popularity in recent years for patients with cardiovascular and metabolic diseases. Despite potential benefits, concerns remain about the safety of the acute response (during and/or within 24 hours postexercise) to a single session of HIIE for these cohorts. Therefore, the aim of this study was to perform a systematic review to evaluate the safety of acute HIIE for people with cardiometabolic diseases. Electronic databases were searched for studies published prior to January 2015, which reported the acute responses of patients with cardiometabolic diseases to HIIE (≥80% peak power output or ≥85% peak aerobic power, VO2peak). Eleven studies met the inclusion criteria (n = 156; clinically stable, aged 27–66 years), with 13 adverse responses reported (~8% of individuals). The rate of adverse responses is somewhat higher compared to the previously reported risk during moderate-intensity exercise. Caution must be taken when prescribing HIIE to patients with cardiometabolic disease. Patients who wish to perform HIIE should be clinically stable, have had recent exposure to at least regular moderate-intensity exercise, and have appropriate supervision and monitoring during and after the exercise session

The effect of exercise-intensity on skeletal muscle stress kinase and insulin protein signaling

Background: Stress and mitogen activated protein kinase (SAPK) signaling play an important role in glucose homeostasis and the physiological adaptation to exercise. However, the effects of acute high-intensity interval exercise (HIIE) and sprint interval exercise (SIE) on activation of these signaling pathways are unclear. Methods: Eight young and recreationally active adults performed a single cycling session of HIIE (5&times;4 minutes at 75% Wmax), SIE (4 &times; 30 second Wingate sprints), and continuous moderate-intensity exercise work-matched to HIIE (CMIE; 30 minutes at 50% of Wmax), separated by a minimum of 1 week. Skeletal muscle SAPK and insulin protein signaling were measured immediately, and 3 hours after exercise. Results: SIE elicited greater skeletal muscle NF-&kappa;B p65 phosphorylation immediately after exercise (SIE: &sim;40%; HIIE: &sim;4%; CMIE; &sim;13%; p &lt; 0.05) compared to HIIE and CMIE. AS160Ser588 phosphorylation decreased immediately after HIIE (&sim;-27%; p &lt; 0.05), and decreased to the greatest extent immediately after SIE (&sim;-60%; p &lt; 0.05). Skeletal muscle JNK (&sim;42%; p &lt; 0.05) and p38 MAPK (&sim;171%; p &lt; 0.05) phosphorylation increased, and skeletal muscle AktSer473 phosphorylation (&sim;-32%; p &lt; 0.05) decreased, to a similar extent immediately after all exercise protocols. AS160Ser588 phosphorylation was similar to baseline three hours after SIE (&sim;-12%; p &gt; 0.05), remained lower 3 hours after HIIE (&sim;-34%; p &lt; 0.05), and decreased 3 hours after CMIE (&sim;-33%; p &lt; 0.05). Conclusion: Despite consisting of less total work than CMIE and HIIE, SIE proved to be an effective stimulus for the activation of stress protein kinase signaling pathways linked to exercise-mediated adaptation of skeletal muscle. Furthermore, post-exercise AS160Ser588 phosphorylation decreased in an exercise-intensity and post-exercise time-course dependent manner

Enhanced skeletal muscle ribosome biogenesis, yet attenuated mTORC1 and ribosome biogenesis-related signalling, following short-term concurrent versus single-mode resistance training

Combining endurance training with resistance training (RT) may attenuate skeletal muscle hypertrophic adaptation versus RT alone; however, the underlying mechanisms are unclear. We investigated changes in markers of ribosome biogenesis, a process linked with skeletal muscle hypertrophy, following concurrent training versus RT alone. Twenty-three males underwent eight weeks of RT, either performed alone (RT group, n = 8), or combined with either high-intensity interval training (HIT+RT group, n = 8), or moderate-intensity continuous training (MICT+RT group, n = 7). Muscle samples (vastus lateralis) were obtained before training, and immediately before, 1 h and 3 h after the final training session. Training-induced changes in basal expression of the 45S ribosomal RNA (rRNA) precursor (45S pre-rRNA), and 5.8S and 28S mature rRNAs, were greater with concurrent training versus RT. However, during the final training session, RT further increased both mTORC1 (p70S6K1 and rps6 phosphorylation) and 45S pre-rRNA transcription-related signalling (TIF-1A and UBF phosphorylation) versus concurrent training. These data suggest that when performed in a training-accustomed state, RT induces further increases mTORC1 and ribosome biogenesis-related signalling in human skeletal muscle versus concurrent training; however, changes in ribosome biogenesis markers were more favourable following a period of short-term concurrent training versus RT performed alon

Acute low-volume high-intensity interval exercise and continuous moderate-intensity exercise elicit a similar improvement in 24-h glycemic control in overweight and obese adults

Background: Acute exercise reduces postprandial oxidative stress and glycemia; however, the effects of exercise intensity are unclear. We investigated the effect of acute low-volume high-intensity interval-exercise (LV-HIIE) and continuous moderate-intensity exercise (CMIE) on glycemic control and oxidative stress in overweight and obese, inactive adults.Methods: Twenty-seven adults were randomly allocated to perform a single session of LV-HIIE (9 females, 5 males; age: 30 &plusmn; 1 years; BMI: 29 &plusmn; 1 kg&middot;m&minus;2; mean &plusmn; SEM) or CMIE (8 females, 5 males; age: 30 &plusmn; 2.0; BMI: 30 &plusmn; 2.0) 1 h after consumption of a standard breakfast. Plasma redox status, glucose and insulin were measured. Continuous glucose monitoring (CGM) was conducted during the 24-h period before (rest day) and after exercise (exercise day).Results: Plasma thiobarbituric acid reactive substances (TBARS; 29 &plusmn;13%, p &lt; 0.01; mean percent change &plusmn;90% confidence limit), hydrogen peroxide (44 &plusmn; 16%, p &lt; 0.01), catalase activity (50 &plusmn; 16%, p &lt; 0.01), and superoxide dismutase activity (21 &plusmn; 6%, p &lt; 0.01) significantly increased 1 h after breakfast (prior to exercise) compared to baseline. Exercise significantly decreased postprandial glycaemia in whole blood (&minus;6 &plusmn; 5%, p &lt; 0.01), irrespective of the exercise protocol. Only CMIE significantly decreased postprandial TBARS (CMIE: &minus;33 &plusmn; 8%, p &lt; 0.01; LV-HIIE: 11 &plusmn; 22%, p = 0.34) and hydrogen peroxide (CMIE: &minus;25 &plusmn; 15%, p = 0.04; LV-HIIE: 7 &plusmn; 26%; p = 0.37). Acute exercise provided a similar significant improvement in 24-h average glucose levels (&minus;5 &plusmn; 2%, p &lt; 0.01), hyperglycemic excursions (&minus;37 &plusmn; 60%, p &lt; 0.01), peak glucose concentrations (&minus;8 &plusmn; 4%, p &lt; 0.01), and the 2-h postprandial glucose response to dinner (&minus;9 &plusmn; 4%, p &lt; 0.01), irrespective of the exercise protocol.Conclusion: Despite elevated postprandial oxidative stress compared to CMIE, LV-HIIE is an equally effective exercise mode for improving 24-h glycemic control in overweight and obese adults

High dietary fat intake increases fat oxidation and reduces skeletal muscle mitochondrial respiration in trained humans.

High-fat, low-carbohydrate (CHO) diets increase whole-body rates of fat oxidation and down-regulate CHO metabolism. We measured substrate utilization and skeletal muscle mitochondrial respiration to determine whether these adaptations are driven by high fat or low CHO availability. In a randomized crossover design, 8 male cyclists consumed 5 d of a high-CHO diet [>70% energy intake (EI)], followed by 5 d of either an isoenergetic high-fat (HFAT; >65% EI) or high-protein diet (HPRO; >65% EI) with CHO intake clamped at <20% EI. During the intervention, participants undertook daily exercise training. On d 6, participants consumed a high-CHO diet before performing 100 min of submaximal steady-state cycling plus an ∼30-min time trial. After 5 d of HFAT, skeletal muscle mitochondrial respiration supported by octanoylcarnitine and pyruvate, as well as uncoupled respiration, was decreased at rest, and rates of whole-body fat oxidation were higher during exercise compared with HPRO. After 1 d of high-CHO diet intake, mitochondrial respiration returned to baseline values in HFAT, whereas rates of substrate oxidation returned toward baseline in both conditions. These findings demonstrate that high dietary fat intake, rather than low-CHO intake, contributes to reductions in mitochondrial respiration and increases in whole-body rates of fat oxidation after a consuming a high-fat, low-CHO diet.-Leckey, J. J., Hoffman, N. J., Parr, E. B., Devlin, B. L., Trewin, A. J., Stepto, N. K., Morton, J. P., Burke, L. M., Hawley, J. A. High dietary fat intake increases fat oxidation and reduces skeletal muscle mitochondrial respiration in trained humans

Complex diseases and co-morbidities: polycystic ovary syndrome and type 2 diabetes mellitus

Objective: Many complex diseases exhibit co-morbidities often requiring management by more than one health specialist. We examined cross-speciality issues that ultimately affect the health and wellbeing of patients with polycystic ovary syndrome (PCOS). PCOS was originally described as a reproductive condition but is now recognised to also be a metabolic and psychological condition affecting 8–13% of women of reproductive age. With a four-fold increased risk of type 2 diabetes (DM2), the Population Attributable Risk of DM2 that could be avoided if PCOS were eliminated is a substantial 19–28% of women of reproductive age. To determine the extent to which PCOS is an important consideration in diabetes development, we examined publications, funding, guidelines and predictors of risk of developing DM2. Results: We found that the topic of PCOS appeared in specialist diabetes journals at only 10% the rate seen in endocrinology journals – about 1 in 500 articles. We found research funding to be substantially less than for diabetes and found that diabetes guidelines and predictive tools for DM2 risk mostly ignore PCOS. This is surprising since insulin resistance in women with PCOS has a different aetiology and additionally women with PCOS are at increased risk of becoming overweight or obese – high risk factors for DM2. Conclusions: We consider the causes of these concerning anomalies and discuss current activities to address the co-morbidities of PCOS, including the recent development of international guidelines, an international PCOS awareness program and potentially changing the name of PCOS to better reflect its metabolic consequences

Physical activity and mental health in women with polycystic ovary syndrome.

Physical activity is prescribed as a component of primary management for Polycystic Ovary Syndrome (PCOS). This study investigates the association between physical activity and mental health as well as the exercise barriers, motivators and support providers for younger women with and without PCOS to assist in physical activity uptake and prescription for these women