Medicine (Western Health) - Research Publications

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    Glucocorticoid-Induced Insulin Resistance in Men Is Associated With Suppressed Undercarboxylated Osteocalcin
    Parker, L ; Lin, X ; Garnham, A ; McConell, G ; Stepto, NK ; Hare, DL ; Byrnes, E ; Ebeling, PR ; Seeman, E ; Brennan-Speranza, TC ; Levinger, I (WILEY, 2019-01-01)
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    Acute exercise alters skeletal muscle mitochondrial respiration and H2O2 emission in response to hyperinsulinemic-euglycemic clamp in middle-aged obese men
    Trewin, AJ ; Levinger, I ; Parker, L ; Shaw, CS ; Serpiello, FR ; Anderson, MJ ; McConell, GK ; Hare, DL ; Stepto, NK ; Philp, A (PUBLIC LIBRARY SCIENCE, 2017-11-21)
    Obesity, sedentary lifestyle and aging are associated with mitochondrial dysfunction and impaired insulin sensitivity. Acute exercise increases insulin sensitivity in skeletal muscle; however, whether mitochondria are involved in these processes remains unclear. The aim of this study was to investigate the effects of insulin stimulation at rest and after acute exercise on skeletal muscle mitochondrial respiratory function (JO2) and hydrogen peroxide emission (JH2O2), and the associations with insulin sensitivity in obese, sedentary men. Nine men (means ± SD: 57 ± 6 years; BMI 33 ± 5 kg.m2) underwent hyperinsulinemic-euglycemic clamps in two separate trials 1-3 weeks apart: one under resting conditions, and another 1 hour after high-intensity exercise (4x4 min cycling at 95% HRpeak). Muscle biopsies were obtained at baseline, and pre/post clamp to measure JO2 with high-resolution respirometry and JH2O2 via Amplex UltraRed from permeabilized fibers. Post-exercise, both JO2 and JH2O2 during ADP stimulated state-3/OXPHOS respiration were lower compared to baseline (P<0.05), but not after subsequent insulin stimulation. JH2O2 was lower post-exercise and after subsequent insulin stimulation compared to insulin stimulation in the rest trial during succinate supported state-4/leak respiration (P<0.05). In contrast, JH2O2 increased during complex-I supported leak respiration with insulin after exercise compared with resting conditions (P<0.05). Resting insulin sensitivity and JH2O2 during complex-I leak respiration were positively correlated (r = 0.77, P<0.05). We conclude that in obese, older and sedentary men, acute exercise modifies skeletal muscle mitochondrial respiration and H2O2 emission responses to hyperinsulinemia in a respiratory state-specific manner, which may have implications for metabolic diseases involving insulin resistance.
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    What Doesn't Kill You Makes You Fitter: A Systematic Review of High-Intensity Interval Exercise for Patients with Cardiovascular and Metabolic Diseases
    Levinger, I ; Shaw, CS ; Stepto, NK ; Cassar, S ; McAinch, AJ ; Cheetham, C ; Maiorana, AJ (SAGE PUBLICATIONS LTD, 2015-01-01)
    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.
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    Acute High-Intensity Interval Exercise-Induced Redox Signaling Is Associated with Enhanced Insulin Sensitivity in Obese Middle-Aged Men
    Parker, L ; Stepto, NK ; Shaw, CS ; Serpiello, PR ; Anderson, M ; Hare, DL ; Levinger, I (FRONTIERS MEDIA SA, 2016-09-16)
    Background: Obesity and aging are associated with increased oxidative stress, activation of stress and mitogen activated protein kinases (SAPK), and the development of insulin resistance and metabolic disease. In contrast, acute exercise also increases oxidative stress and SAPK signaling, yet is reported to enhance insulin sensitivity and reduce the risk of metabolic disease. This study explored this paradox by investigating the effect of a single session of high-intensity interval-exercise (HIIE) on redox status, muscle SAPK and insulin protein signaling in eleven middle-aged obese men. Methods: Participants completed a 2 h hyperinsulinaemic-euglycaemic clamp at rest, and 60 min after HIIE (4 × 4 mins at 95% HRpeak; 2 min recovery periods), separated by 1-3 weeks. Results: Irrespective of exercise-induced changes to redox status, insulin stimulation both at rest and after HIIE similarly increased plasma superoxide dismutase activity, plasma catalase activity, and skeletal muscle 4-HNE; and significantly decreased plasma TBARS and hydrogen peroxide. The SAPK signaling pathways of p38 MAPK, NF-κB p65, and JNK, and the distal insulin signaling protein AS160Ser588, were activated with insulin stimulation at rest and to a greater extent with insulin stimulation after a prior bout of HIIE. Higher insulin sensitivity after HIIE was associated with higher insulin-stimulated SOD activity, JNK, p38 MAPK and NF-κB phosphorylation (r = 0.63, r = 0.71, r = 0.72, r = 0.71; p < 0.05, respectively). Conclusion:These findings support a role for redox homeostasis and SAPK signaling in insulin-stimulated glucose uptake which may contribute to the enhancement of insulin sensitivity in obese men 3 h after HIIE.
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    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.
    Parker, L ; Shaw, CS ; Banting, L ; Levinger, I ; Hill, KM ; McAinch, AJ ; Stepto, NK (Frontiers Media SA, 2016)
    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 ± 1 years; BMI: 29 ± 1 kg·m-2; mean ± SEM) or CMIE (8 females, 5 males; age: 30 ± 2.0; BMI: 30 ± 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 ±13%, p < 0.01; mean percent change ±90% confidence limit), hydrogen peroxide (44 ± 16%, p < 0.01), catalase activity (50 ± 16%, p < 0.01), and superoxide dismutase activity (21 ± 6%, p < 0.01) significantly increased 1 h after breakfast (prior to exercise) compared to baseline. Exercise significantly decreased postprandial glycaemia in whole blood (-6 ± 5%, p < 0.01), irrespective of the exercise protocol. Only CMIE significantly decreased postprandial TBARS (CMIE: -33 ± 8%, p < 0.01; LV-HIIE: 11 ± 22%, p = 0.34) and hydrogen peroxide (CMIE: -25 ± 15%, p = 0.04; LV-HIIE: 7 ± 26%; p = 0.37). Acute exercise provided a similar significant improvement in 24-h average glucose levels (-5 ± 2%, p < 0.01), hyperglycemic excursions (-37 ± 60%, p < 0.01), peak glucose concentrations (-8 ± 4%, p < 0.01), and the 2-h postprandial glucose response to dinner (-9 ± 4%, p < 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.
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    The effectiveness of high intensity intermittent training on metabolic, reproductive and mental health in women with polycystic ovary syndrome: study protocol for the iHIT- randomised controlled trial
    Hiam, D ; Patten, R ; Gibson-Helm, M ; Moreno-Asso, A ; McIlvenna, L ; Levinger, I ; Harrison, C ; Moran, LJ ; Joham, A ; Parker, A ; Shorakae, S ; Simar, D ; Stepto, N (BMC, 2019-04-16)
    BACKGROUND: Polycystic ovary syndrome (PCOS) is a reproductive-metabolic condition. Insulin resistance is a hallmark of PCOS and is related to increased hyperandrogenism that drives inherent metabolic, reproductive and psychological features of the syndrome. Insulin resistance in women with PCOS is managed by weight loss, lifestyle interventions (i.e. exercise, diet) and insulin-sensitising medications. This manuscript describes the protocol of our study evaluating the effectiveness of high intensity intermittent training (HIIT) or moderate intensity exercise on cardiometabolic, reproductive and mental health in overweight women with PCOS. METHODS/DESIGN: We will employ a three arm, parallel-group, randomised controlled trial recruiting 60 women diagnosed with PCOS, aged between 18 and 45 years and with a body mass index (BMI) greater than 25 kg/m2. Following screening and baseline testing, women will be randomised by simple randomisation procedure using computer generated sequence allocation to undergo one of two 12-week supervised interventions: either HIIT or moderate intensity exercise (standard supervised exercise), or to standard care [Con] (unsupervised lifestyle advice) at a 1:1:1 allocation ratio. The primary outcome for this trial is to measure the improvements in metabolic health; specifically changes in insulin sensitivity in response to different exercise intensities. Baseline and post-intervention testing include anthropometric measurements, cardiorespiratory fitness testing, reproductive hormone profiles (anti-müllerian hormone and steroid profiles), metabolic health, health-related quality of life and mental health questionnaires and objective and subjective lifestyle monitoring. Reporting of the study will follow the CONSORT statement. DISCUSSION: This trial aims to demonstrate the comparative efficacy and maintenance of different exercise intensities to advance the understanding of PCOS management and provide insight into the optimal exercise intensity for improved cardiometabolic outcomes. Secondary outcomes will include the impact of different exercise protocols on reproductive hormone profiles, mental health and health-related quality of life. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12615000242527 . Registered on 17 March 2015.
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    Exercise and Glycemic Control: Focus on Redox Homeostasis and Redox-Sensitive Protein Signaling
    Parker, L ; Shaw, CS ; Stepto, NK ; Levinger, I (FRONTIERS MEDIA SA, 2017-05-05)
    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.
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    The effect of exercise-intensity on skeletal muscle stress kinase and insulin protein signaling
    Parker, L ; Trewin, A ; Levinger, I ; Shaw, CS ; Stepto, NK ; Philp, A (PUBLIC LIBRARY SCIENCE, 2017-02-09)
    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 x 4 minutes at 75% Wmax), SIE (4 x 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-κB p65 phosphorylation immediately after exercise (SIE: ~40%; HIIE: ~4%; CMIE; ~13%; p < 0.05) compared to HIIE and CMIE. AS160Ser588 phosphorylation decreased immediately after HIIE (~-27%; p < 0.05), and decreased to the greatest extent immediately after SIE (~-60%; p < 0.05). Skeletal muscle JNK (~42%; p < 0.05) and p38 MAPK (~171%; p < 0.05) phosphorylation increased, and skeletal muscle AktSer473 phosphorylation (~-32%; p < 0.05) decreased, to a similar extent immediately after all exercise protocols. AS160Ser588 phosphorylation was similar to baseline three hours after SIE (~-12%; p > 0.05), remained lower 3 hours after HIIE (~-34%; p < 0.05), and decreased 3 hours after CMIE (~-33%; p < 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.