Beta2-agonist impairs muscle insulin sensitivity in persons with insulin resistance.

CONTEXT: Given the promising effects of prolonged treatment with beta2-agonist on insulin sensitivity in animals and non-diabetic individuals, the beta2-adrenergic receptor has been proposed as a target to counter peripheral insulin resistance. On the other hand, rodent studies also reveal that beta2-agonists acutely impair insulin action, posing a potential caveat for their use in treating insulin resistance. OBJECTIVE: To assess the impact of beta2-agonist on muscle insulin action and glucose metabolism and identify the underlying mechanism(s) in 10 insulin-resistant subjects. METHODS AND PARTICIPANTS: In a cross-over design, we assessed the effect of beta2-agonist on insulin-stimulated muscle glucose uptake during a 3-h hyperinsulinemic isoglycemic clamp with and without intralipid infusion in 10 insulin-resistant overweight subjects. Two hours into the clamp, we infused beta2-agonist. We collected muscle biopsies before, two hours into and by the end of the clamp and analyzed them using metabolomic and lipidomic techniques. RESULTS: We establish that beta2-agonist, independently from and additively to intralipid, impairs insulin-stimulated muscle glucose uptake via different mechanisms. In combination, beta2-agonist and intralipid nearly eliminates insulin-dependent muscle glucose uptake. While both beta2-agonist and intralipid elevated muscle glucose-6-phosphate, only intralipid caused accumulation of downstream muscle glycolytic intermediates, whereas beta2-agonist attenuated incorporation of glucose into glycogen. CONCLUSIONS: Our findings suggest that beta2-agonist inhibits glycogenesis while intralipid inhibits glycolysis in skeletal muscle of insulin-resistant individuals. These results should be addressed in future treatment of insulin resistance with beta2-agonist.

No additive effect of creatine, caffeine, and sodium bicarbonate on intense exercise performance in endurance-trained individuals.

BACKGROUND: Athletes commonly use creatine, caffeine, and sodium bicarbonate for performance enhancement. While their isolated effects are well-described, less is known about their potential additive effects. METHODS: Following a baseline trial, we randomized 12 endurance-trained males (age: 25 ± 5 years, VO2max: 56.7 ± 4.6 mL kg-1 min-1; mean ± SD) and 11 females (age: 25 ± 3 years, VO2max: 50.2 ± 3.4 mL kg-1 min-1) to 5 days of creatine monohydrate (0.3 g kg-1 per day) or placebo loading, followed by a daily maintenance dose (0.04 g kg-1) throughout the study. After the loading period, subjects completed four trials in randomized order where they ingested caffeine (3 mg kg-1), sodium bicarbonate (0.3 g kg-1), placebo, or both caffeine and sodium bicarbonate before a maximal voluntary contraction (MVC), 15-s sprint, and 6-min time trial. RESULTS: Compared to placebo, mean power output during 15-s sprint was higher following loading with creatine than placebo (+34 W, 95% CI: 10 to 58, p = 0.008), but with no additional effect of caffeine (+10 W, 95% CI: -7 to 24, p = 0.156) or sodium bicarbonate (+5 W, 95% CI: -4 to 13, p = 0.397). Mean power output during 6-min time trial was higher with caffeine (+12 W, 95% CI: 5 to 18, p = 0.001) and caffeine + sodium bicarbonate (+8 W, 95% CI: 0 to 15, p = 0.038), whereas sodium bicarbonate (-1 W, 95% CI: -7 to 6, p = 0.851) and creatine (-6 W, 95% CI: -15 to 4, p = 0.250) had no effects. CONCLUSION: While creatine and caffeine can enhance sprint- and time trial performance, respectively, these effects do not seem additive. Therefore, supplementing with either creatine or caffeine appears sufficient to enhance sprint or short intense exercise performance.

Low-Volume Speed Endurance Training with Reduced Volume Improves Short-Term Exercise Performance in Highly Trained Cyclists.

PURPOSE: We investigated the effects of low and high volume speed endurance training (SET), with a reduced training volume, on sprint ability, short- and long-term exercise capacity, muscle mitochondrial properties, ion transport proteins and maximal enzyme activity in highly trained athletes. METHODS: Highly-trained male cyclists (V̇O2max: 68.3 ± 5.0 mL × min-1 × kg-1, n = 24) completed six weeks of either low (SET-L; 6x30-s intervals, n = 8) or high (SET-H; 12 × 30-s intervals, n = 8) volume SET twice per week with a 30%-reduction in training volume. A control group (CON, n = 8) maintained their training. Exercise performance was evaluated by i) 6-s sprinting, ii) a 4-min time trial, iii) a 60-min preload at 60% V̇O2max followed by a 20-min time trial. A biopsy of m. vastus lateralis was collected before and after the training intervention. RESULTS: In SET-L, 4-min time trial performance was improved (P < 0.05) by 3.8%, with no change in SET-H and CON. Sprint ability, prolonged endurance exercise capacity, V̇O2max, muscle mitochondrial respiratory capacity, maximal citrate synthase activity, fiber-type specific mitochondrial proteins (complex I - V) and PFK content did not change in any of the groups. In SET-H, maximal activity of muscle PFK and abundance of Na+-K+ pump-subunit α1, α2, ß1, and phospholemman (FXYD1) were 20%, 50%, 19%, 24%, and 42 % higher (P < 0.05), respectively after compared to before the intervention, with no changes in SET-L or CON. CONCLUSIONS: Low SET volume combined with a reduced aerobic low and moderate intensity training volume does improve short duration intense exercise performance and maintain sprinting ability, V̇O2max, endurance exercise performance and muscle oxidative capacity, whereas, high volume of SET appears necessary to upregulate muscle ion transporter content and maximal PFK activity in highly trained cyclists.

Importance of training volume during intensified training in elite cyclists: Maintained vs. reduced volume at moderate intensity.

INTRODUCTION: Male elite cyclists (average VO2 -max: 71 mL/min/kg, n = 18) completed 7 weeks of high-intensity interval training (HIT) (3×/week; 4-min and 30-s intervals) during the competitive part of the season. The influence of a maintained or lowered total training volume combined with HIT was evaluated in a two-group design. Weekly moderate-intensity training was lowered by ~33% (~5 h) (LOW, n = 8) or maintained at normal volume (NOR, n = 10). Endurance performance and fatigue resistance were evaluated via 400 kcal time-trials (~20 min) commenced either with or without prior completion of a 120-min preload (including repeated 20-s sprints to simulate physiologic demands during road races). RESULTS: Time-trial performance without preload was improved after the intervention (p = 0.006) with a 3% increase in LOW (p = 0.04) and a 2% increase in NOR (p = 0.07). Preloaded time-trial was not significantly improved (p = 0.19). In the preload, average power during repeated sprinting increased by 6% in LOW (p < 0.01) and fatigue resistance in sprinting (start vs end of preload) was improved (p < 0.05) in both groups. Blood lactate during the preload was lowered (p < 0.001) solely in NOR. Measures of oxidative enzyme activity remained unchanged, whereas the glycolytic enzyme PFK increased by 22% for LOW (p = 0.02). CONCLUSION: The present study demonstrates that elite cyclists can benefit from intensified training during the competitive season both with maintained and lowered training volume at moderate intensity. In addition to benchmarking the effects of such training in ecological elite settings, the results also indicate how some performance and physiological parameters may interact with training volume.

Similar improvements in 5-km performance and maximal oxygen uptake with submaximal and maximal 10-20-30 training in runners, but increase in muscle oxidative phosphorylation occur only with maximal effort training.

OBJECTIVE: The aim of the present study was to examine whether 10-20-30 training (consecutive 1-min intervals consisting of 30 s at low-speed, 20 s at moderate-speed, and 10 s at high-speed), performed with submaximal effort during the 10-s high-speed runs, would lead to improved performance as well as increased maximum oxygen uptake (VO2 -max) and muscle oxidative phosphorylation (OXPHOS). In addition, to examine to what extent the effects would compare to 10-20-30 running conducted with maximal effort. DESIGN: Nineteen males were randomly assigned to 10-20-30 running performed with either submaximal (SUBMAX; n = 11) or maximal (MAX; n = 8) effort, which was conducted three times/week for 6 weeks (intervention; INT). Before and after INT, subjects completed a 5-km running test and a VO2 -max test, and a biopsy was obtained from m. vastus lateralis. RESULTS: After compared to before INT, SUBMAX and MAX improved (p < 0.05) 5-km performance by 3.0% (20.8 ± 0.4 (means±SE) vs. 21.5 ± 0.4 min) and 2.3% (21.2 ± 0.4 vs. 21.6 ± 0.4 min), respectively, and VO2 -max was ~7% higher (p < 0.01) in both SUBMAX (57.0 ± 1.3 vs. 53.5 ± 1.1 mL/min/kg) and MAX (57.8 ± 1.2 vs. 53.7 ± 0.9 mL/min/kg), with no difference in the changes between groups. In SUBMAX, muscle OXPHOS was unchanged, whereas in MAX, muscle OXPHOS subunits (I-IV) and total OXPHOS (5.5 ± 0.3 vs 4.7 ± 0.3 A.U.) were 9%-29% higher (p < 0.05) after compared to before INT. CONCLUSION: Conducting 10-20-30 training with a non-maximal effort during the 10-s high-speed runs is as efficient in improving 5-km performance and VO2 -max as maximal effort exercise, whereas increase in muscle OXPHOS occur only when the 10-s high-speed runs are performed with maximal effort.

Inhaled beta2 -agonist, formoterol, enhances intense exercise performance, and sprint ability in elite cyclists.

PURPOSE: Many athletes use long-acting beta2 -agonist formoterol in treatment of asthma. However, studies in non-athlete cohorts demonstrate that inhaled formoterol can enhance sprint performance calling into question whether its use in competitive sports should be restricted. We investigated whether formoterol at upper recommended inhaled doses (54 µg) would enhance sprint ability and intense exercise performance in elite cyclists. METHODS: Twenty-one male cyclists (V̇O2max : 70.4 ± 4.3 mL × min-1 × kg-1 , mean ± SD) completed two 6-s all-out sprints followed by 4-min all-out cycling after inhaling either 54 µg formoterol or placebo. We also assessed cyclists' leg muscle mass by dual-energy X-ray absorptiometry and muscle fiber type distribution of vastus lateralis biopsies. RESULTS: Peak and mean power output during the 6-s sprint was 32 W (95% CI, 19-44 W, p < 0.001) and 36 W (95% CI, 24-48 W, p < 0.001) higher with formoterol than placebo, corresponding to an enhancing effect of around 3%. Power output during 4-min all-out cycling was 9 W (95% CI, 2-16 W, p = 0.01) greater with formoterol than placebo, corresponding to an enhancing effect of 2.3%. Performance changes in response to formoterol were unrelated to cyclists' VO2max and leg lean mass, whereas muscle fiber Type I distribution correlated with change in sprinting peak power in response to formoterol (r2 = 0.314, p = 0.012). CONCLUSION: Our findings demonstrate that an inhaled one-off dose of 54 µg formoterol has a performance-enhancing potential on sprint ability and short intense performance in elite male cyclists, which is irrespective of training status but partly related to muscle fiber type distribution for sprint ability.

Inhaled salbutamol induces leanness in well-trained healthy females but not males during a period of endurance training: a randomised controlled trial.

Introduction: Many athletes use short-acting inhaled ß2-agonists multiple times weekly during training sessions to prevent exercise-induced bronchoconstriction, but it is unclear if treatment impairs training outcomes. Herein, we investigated performance adaptations in well-trained females and males training with prior inhalation of salbutamol. Methods: 19 females and 21 males with maximal oxygen uptake (V'O2max) of 50.5±3.3 and 57.9±4.9 mL·min-1·kg-1, respectively, participated in this double-blinded, placebo-controlled, parallel-group study. We randomised participants to placebo or salbutamol inhalation (800-1600 µg·training day-1) for 6 weeks of combined endurance (1× per week) and high-intensity interval training (2× per week). We assessed participants' body composition, V'O2max and muscle contractile function, and collected vastus lateralis muscle biopsies. Results: Salbutamol induced a sex-specific loss of whole-body fat mass (sex×treatment: p=0.048) where only salbutamol-treated females had a fat mass reduction compared to placebo (-0.8 kg at 6 weeks; 95% CI: -0.5 to -1.6; p=0.039). Furthermore, salbutamol-treated females exhibited a repartitioning effect, lowering fat mass while gaining lean mass (p=0.011), which was not apparent for males (p=0.303). Salbutamol negatively impacted V'O2max in both sexes (treatment main effect: p=0.014) due to a blunted increase in V'O2max during the initial 4 weeks of the intervention. Quadriceps contractile strength was impaired in salbutamol-treated females (-39 N·m; 95% CI: -61 to -17; p=0.002) compared to placebo at 6 weeks. Muscle electron transport chain complex I-V abundance increased with salbutamol (treatment main effect: p=0.035), while content of SERCAI, ß2-adrenoceptor and desmin remained unchanged. Conclusion: Inhaled salbutamol appears to be an effective repartitioning agent in females but may impair aerobic and strength-related training outcomes.

Exercise training induces thrombogenic benefits in recent but not late postmenopausal females.

Although regular physical activity is known to improve cardiovascular health in men, evidence for its beneficial effects in postmenopausal females is less convincing and it remains unclear whether initiation of exercise training soon after, rather than many years after menopause impacts the magnitude of training-induced adaptations. We evaluated exercise-induced changes in markers of thrombotic risk and conduit artery function in recent≤5yr compared with late≥10yr postmenopausal females. Fourteen recent≤5yr and 13 late≥10yr healthy postmenopausal females completed 8 wk of regular intensive exercise training, consisting of floorball and cycling. Markers of thrombotic risk and vascular health were assessed before and after the intervention, and data were analyzed using a linear mixed model. Exercise training reduced markers of thrombotic risk, including an 11% reduction (P = 0.007) in agonist-induced platelet reactivity and a reduction (P = 0.027) in incipient clot microstructure (∼40% reduction in clot mass) in the recent≤5yr but not the late≥10yr (P = 0.380; P = 0.739, respectively) postmenopausal females. There was no change in conduit artery function, as measured by brachial (recent≤5yr, P = 0.804; late≥10yr, P = 0.311) and popliteal artery (recent≤5yr, P = 0.130; late≥10yr, P = 0.434) flow-mediated dilation. Only the late≥10yr postmenopausal females exhibited an increase (by 9.6%, P = 0.022) in intracellular adhesion molecule-1 levels after training, which may have impacted the thrombogenic adaptation in this group. These findings suggest that 8 wk of high-intensity exercise training reduces thrombotic risk in recent≤5yr, but not late≥10yr postmenopausal females. Thus, regular physical activity initiated soon after, rather than many years after menopause and at a higher age, may be more efficient for reducing thrombogenic risk.NEW & NOTEWORTHY Eight weeks of high-intensity exercise training reduces platelet reactivity as well as blood clot density and strength in females ≤5 yr past menopause but not in females ≥10 yr past menopause. The divergent response in the late postmenopausal females may be explained by training-induced low-grade systemic inflammation. These findings suggest that regular physical activity initiated soon after menopause, compared with many years after menopause, may be more efficient for reducing the risk of blood clots.

Inhaled formoterol impairs aerobic exercise capacity in endurance-trained individuals: a randomised controlled trial.

Background: The 2022 Global Initiative for Asthma guidelines emphasise the inhaled long-acting ß2-agonist formoterol as part of the first treatment step, and therefore formoterol use among athletes will probably increase. However, prolonged supratherapeutic use of inhaled ß2-agonists impairs training outcomes in moderately trained men. We investigated whether inhaled formoterol, at therapeutic doses, imposes detrimental effects in endurance-trained individuals of both sexes. Methods: 51 endurance-trained participants (31 male, 20 female; mean±sd maximal oxygen consumption (V̇ O2 max) 62±6 mL·min-1·kg bw-1 and 52±5 mL·min-1·kg bw-1, respectively) inhaled formoterol (24 µg; n=26) or placebo (n=25) twice daily for 6 weeks. At baseline and follow-up, we assessed V̇ O2 max and incremental exercise performance during a bike-ergometer ramp-test; body composition by dual-energy X-ray absorptiometry; muscle oxidative capacity by high-resolution mitochondrial respirometry, enzymatic activity assays and immunoblotting; intravascular volumes by carbon monoxide rebreathing; and cardiac left ventricle mass and function by echocardiography. Results: Compared to placebo, formoterol increased lean body mass by 0.7 kg (95% CI 0.2-1.2 kg; treatment×trial p=0.022), but decreased V̇ O2 max by 5% (treatment×trial p=0.013) and incremental exercise performance by 3% (treatment×trial p<0.001). In addition, formoterol lowered muscle citrate synthase activity by 15% (treatment×trial p=0.063), mitochondrial complex II and III content (treatment×trial p=0.028 and p=0.007, respectively), and maximal mitochondrial respiration through complexes I and I+II by 14% and 16% (treatment×trial p=0.044 and p=0.017, respectively). No apparent changes were observed in cardiac parameters and intravascular blood volumes. All effects were sex-independent. Conclusion: Our findings demonstrate that inhaled therapeutic doses of formoterol impair aerobic exercise capacity in endurance-trained individuals, which is in part related to impaired muscle mitochondrial oxidative capacity. Thus, if low-dose formoterol fails to control respiratory symptoms in asthmatic athletes, physicians may consider alternative treatment options.

High-Intensity Training Represses FXYD5 and Glycosylates Na,K-ATPase in Type II Muscle Fibres, Which Are Linked with Improved Muscle K+ Handling and Performance.

Na+/K+ ATPase (NKA) comprises several subunits to provide isozyme heterogeneity in a tissue-specific manner. An abundance of NKA α, ß, and FXYD1 subunits is well-described in human skeletal muscle, but not much is known about FXYD5 (dysadherin), a regulator of NKA and ß1 subunit glycosylation, especially with regard to fibre-type specificity and influence of sex and exercise training. Here, we investigated muscle fibre-type specific adaptations in FXYD5 and glycosylated NKAß1 to high-intensity interval training (HIIT), as well as sex differences in FXYD5 abundance. In nine young males (23.8 ± 2.5 years of age) (mean ± SD), 3 weekly sessions of HIIT for 6 weeks enhanced muscle endurance (220 ± 102 vs. 119 ± 99 s, p < 0.01) and lowered leg K+ release during intense knee-extensor exercise (0.5 ± 0.8 vs. 1.0 ± 0.8 mmol·min-1, p < 0.01) while also increasing cumulated leg K+ reuptake 0-3 min into recovery (2.1 ± 1.5 vs. 0.3 ± 0.9 mmol, p < 0.01). In type IIa muscle fibres, HIIT lowered FXYD5 abundance (p < 0.01) and increased the relative distribution of glycosylated NKAß1 (p < 0.05). FXYD5 abundance in type IIa muscle fibres correlated inversely with the maximal oxygen consumption (r = -0.53, p < 0.05). NKAα2 and ß1 subunit abundances did not change with HIIT. In muscle fibres from 30 trained males and females, we observed no sex (p = 0.87) or fibre type differences (p = 0.44) in FXYD5 abundance. Thus, HIIT downregulates FXYD5 and increases the distribution of glycosylated NKAß1 in type IIa muscle fibres, which is likely independent of a change in the number of NKA complexes. These adaptations may contribute to counter exercise-related K+ shifts and enhance muscle performance during intense exercise.

Effect of sample fractionation and normalization when immunoblotting for human muscle Na+/K+-ATPase subunits and glycogen synthase.

Immunoblotting is widely used in muscle physiology to determine protein regulation and abundance. However, research groups use different protocols, which may result in differential outcomes. Herein, we investigated the effect of various homogenization procedures on determination of protein abundance in human m. vastus lateralis biopsies. Furthermore, we investigated differences in abundance between young healthy males (n = 12) and type-2 diabetics (n = 4), and the effect of data normalization. Fractionated lysates had the lowest variation in total protein determination as compared to non-fractionated homogenates. Abundance of NKAα2, NKAß1, FXYD1, and glycogen synthase was higher (P < 0.05) in young healthy than in type-2 diabetics determined in both fractionated and non-fractionated samples for which normalization to the stain-free signal and/or standard curve did not affect outcomes. Precision and reliability of protein abundance determination between sample types showed a moderate to good reliability for these proteins, whereas the commonly used house-keeping protein, actin, showed poor reliability. In conclusion, fractionated and non-fractionated immunoblotting samples yield similar data for several sarcolemmal and cytosolic proteins, except for actin, which, therefore appears inappropriate for data normalization in immunoblotting of human skeletal muscle. Thus, fractionation does not seem to be a major source of bias when immunoblotting for NKA subunits and GS.

Performance Adaptations to Intensified Training in Top-Level Football.

Because physical demands are surging in football (soccer, USA), clubs are more and more seeking players who have a high capacity to perform repeated intense exercise. High-intensity interval training (HIIT), comprising exercise performed at intensities near or exceeding the capacity of aerobic energy systems, effectively enhances the physical conditioning of players. But given that HIIT imposes high loads, it increases the risk of overload-associated match performance decline and injury. This makes some coaches inclined to conduct HIIT in the weeks leading up to the season and during the season. Therefore, the challenge is how to optimize and dose HIIT during these phases, as they can be decisive. Studies have highlighted the utility of conducting periods of intensified training to overcome the risk of overload while at the same time enhancing performance. During intensified training periods of typically a few weeks, intensity is increased by enlarging the amount of HIIT, for example, aerobic high-intensity training or speed endurance training, while volume at low-to-moderate intensity is significantly reduced. The outcome depends on training composition and prescription-most notably, intensity and duration of bouts and recovery. When work intervals are prescribed for a few minutes at intensities > 90% heart rate max (i.e., aerobic high-intensity training), then beneficial adaptations pertaining to aerobic power and capacity are apparent. But when work intervals are conducted at much higher intensities, as all-out efforts or sprinting of typically 10- to 40-s duration with longer recovery periods (i.e., speed endurance training), beneficial adaptations pertaining to anaerobic energy systems, ion handling, and fatigue resilience are commonly observed. In this review, we discuss the utility of conducting intensified training periods to enhance performance in elite football players during the late preparation phase and competitive season.

The effect of 5 years of team sport on elderly males' health and social capital-An interdisciplinary follow-up study.

Background and Aims: Floorball training induces positive effects on health among untrained older adults. However, the effect of long-term participation (>2 years) in floorball training among elderly males has not been investigated. The aim of the present study was to examine the effect of 5 years of floorball training on risk factors for lifestyle diseases, fitness, physical function, and social capital of elderly males and compare to a control group that continued their usual lifestyle. Methods: Twenty-nine recreationally active elderly men aged 75.1 ± 3.3 (mean ± SD; range: 69-81) years with a height, body mass, and body mass index of 1.78 ± 0.06 m, 79.8 ± 10.9 kg, and 25.8 ± 4.1 kg/m2, respectively, volunteered to take part in follow-up investigations about 5 years after participating in a study on the effect of 12 weeks of floorball or petanque training. At the end of the parental study 15 subjects chose to participate in floorball training (floorball group [FG]) whereas 14 subjects (control group [CG]), resumed their usual lifestyle. FG participated in small-sided floorball training 1 h ~1.75 times/week for 5 years in a local sports club. Results: From baseline to 5 years, FG had reduced fat percentage, android, and visceral fat, increased total and leg bone mineral density, leg extension maximal voluntary contraction, maximal walk distance in 6 min and 30 s sit-to-stand repetitions, decreased time for 5 sit-to-stand repetitions and Timed Up and Go (p < 0.05). These changes were all different from less favorable changes in CG (p < 0.05). In FG there was a decline in maximum oxygen uptake which was smaller than the decline in CG (p < 0.05). In addition, FG had developed social capital through the 5 years strengthening their social connectedness and group cohesion. Conclusion: In conclusion, both from a sociological and physiological perspective, small-sided floorball training can be considered a health-promoting activity for older men.

Four Weeks of Intensified Training Enhances On-Ice Intermittent Exercise Performance and Increases Maximal Oxygen Consumption of Youth National-Team Ice Hockey Players.

PURPOSE: We investigated whether 4 weeks of intensified training consisting of speed endurance training (SET) enhanced high-intensity exercise performance in youth national-team ice hockey players. METHODS: Utilizing a randomized crossover design, we subjected 17 players to 4 weeks of SET, comprising 6 to 10 × 20 seconds at maximal effort (>95% maximum ice skating speed) with 120-second recovery performed 3 times weekly, or maintenance of regular training (control period). Before and after each period, players completed ice-hockey-specific tests on ice, including a Yo-Yo Intermittent Recovery Level 1 test, a 30-m sprint test, and an agility test. On a separate day, players were assessed for body composition with dual-energy X-ray absorptiometry and performed countermovement jump, maximal voluntary isometric knee extensor contraction, a 15-second maximal sprint test, and a submaximal and incremental test on a bike ergometer in which pulmonary oxygen consumption was determined. RESULTS: Yo-Yo Intermittent Recovery Level 1 test performance increased (P < .001) by 14% (95% CI, 201-496 m) during the SET period. Maximal pulmonary oxygen consumption (P < .05) and time to exhaustion (P < .05) were 4.8% and 6.5% higher, respectively, after the SET period than before. Fat-free mass increased (P < .01) during the SET period by 1.7 kg (95% CI, 1.0-2.5), whereas fat mass remained unchanged. These effects were superior to the control period. CONCLUSIONS: These findings underpin the effectiveness of SET for improving on-ice high-intensity performance and highlight that elite ice hockey players can benefit from implementing SET.

High-intensity interval training remodels the proteome and acetylome of human skeletal muscle.

Exercise is an effective strategy in the prevention and treatment of metabolic diseases. Alterations in the skeletal muscle proteome, including post-translational modifications, regulate its metabolic adaptations to exercise. Here, we examined the effect of high-intensity interval training (HIIT) on the proteome and acetylome of human skeletal muscle, revealing the response of 3168 proteins and 1263 lysine acetyl-sites on 464 acetylated proteins. We identified global protein adaptations to exercise training involved in metabolism, excitation-contraction coupling, and myofibrillar calcium sensitivity. Furthermore, HIIT increased the acetylation of mitochondrial proteins, particularly those of complex V. We also highlight the regulation of exercise-responsive histone acetyl-sites. These data demonstrate the plasticity of the skeletal muscle proteome and acetylome, providing insight into the regulation of contractile, metabolic and transcriptional processes within skeletal muscle. Herein, we provide a substantial hypothesis-generating resource to stimulate further mechanistic research investigating how exercise improves metabolic health.

Beta2 -agonist increases skeletal muscle interleukin 6 production and release in response to resistance exercise in men.

OBJECTIVE: Several tissues produce and release interleukin-6 (IL-6) in response to beta2 -adrenergic stimulation with selective agonists (beta2 -agonists). Moreover, exercise stimulates muscle IL-6 production, but whether beta2 -agonists regulate skeletal muscle production and release of IL-6 in humans in association with exercise remains to be clarified. Thus, we investigated leg IL-6 release in response to beta2 -agonist salbutamol in lean young men at rest and in recovery from resistance exercise. DESIGN: The study employed a randomized controlled crossover design, where 12 men ingested either salbutamol (16 mg) or placebo for 4 days, followed by the last dose (24 mg) administered 1½ h before exercise. Arterial and femoral venous plasma IL-6 as well as femoral artery blood flow was measured before and ½-5 h in recovery from quadriceps muscle resistance exercise. Furthermore, vastus lateralis muscle biopsies were collected ½ and 5 h after exercise for determination of mRNA levels of IL-6 and Tumor Necrosis Factor (TNF)-α. RESULTS: Average leg IL-6 release was 1.7-fold higher (p = 0.01) for salbutamol than placebo, being 138 ± 76 and 79 ± 66 pg min-1 (mean ± SD) for salbutamol and placebo, respectively, but IL-6 release was not significantly different between treatments within specific sampling points at rest and after exercise. Muscle IL-6 mRNA was 1.5- and 1.7-fold higher (p = 0.001) for salbutamol than placebo ½ and 5 h after exercise, respectively, whereas no significant treatment differences were observed for TNF-α mRNA. CONCLUSIONS: Beta2 -adrenergic stimulation with high doses of the selective beta2 -agonist salbutamol, preceeded by 4 consecutive daily doses, induces transcription of IL-6 in skeletal muscle in response to resistance exercise, and increases muscle IL-6 release in lean individuals.

Active Relative to Passive Ischemic Preconditioning Enhances Intense Endurance Performance in Well-Trained Men.

PURPOSE: This study tested the hypothesis of whether ischemic exercise preconditioning (IPC-Ex) elicits a better intense endurance exercise performance than traditional ischemic preconditioning at rest (IPC-rest) and a SHAM procedure. METHODS: Twelve men (average V˙O2max ∼61 mL·kg-1·min-1) performed 3 trials on separate days, each consisting of either IPC-Ex (3 × 2-min cycling at ∼40 W with a bilateral-leg cuff pressure of ∼180 mm Hg), IPC-rest (4 × 5-min supine rest at 220 mm Hg), or SHAM (4 × 5-min supine rest at <10 mm Hg) followed by a standardized warm-up and a 4-minute maximal cycling performance test. Power output, blood lactate, potassium, pH, rating of perceived exertion, oxygen uptake, and gross efficiency were assessed. RESULTS: Mean power during the performance test was higher in IPC-Ex versus IPC-rest (+4%; P = .002; 95% CI, +5 to 18 W). No difference was found between IPC-rest and SHAM (-2%; P = .10; 95% CI, -12 to 1 W) or between IPC-Ex and SHAM (+2%; P = .09; 95% CI, -1 to 13 W). The rating of perceived exertion increased following the IPC-procedure in IPC-Ex versus IPC-rest and SHAM (P < .001). During warm-up, IPC-Ex elevated blood pH versus IPC-rest and SHAM (P ≤ .027), with no trial differences for blood potassium (P > .09) or cycling efficiency (P ≥ .24). Eight subjects anticipated IPC-Ex to be best for their performance. Four subjects favored SHAM. CONCLUSIONS: Performance in a 4-minute maximal test was better following IPC-Ex than IPC-rest and tended to be better than SHAM. The IPC procedures did not affect blood potassium, while pH was transiently elevated only by IPC-Ex. The performance-enhancing effect of IPC-Ex versus IPC-rest may be attributed to a placebo effect, improved pH regulation, and/or a change in the perception of effort.

Muscle hypertrophic effect of inhaled beta2 -agonist is associated with augmented insulin-stimulated whole-body glucose disposal in young men.

Rodent studies highlight enhancement of glucose tolerance and insulin sensitivity as potential clinically relevant effects of chronic beta2 -agonist treatment. However, the doses administered to rodents are not comparable with the therapeutic doses used for humans. Thus, we investigated the physiological effects of prolonged beta2 -agonist treatment at inhaled doses resembling those used in respiratory diseases on insulin-stimulated whole-body glucose disposal and putative mechanisms in skeletal muscle and adipose tissue of healthy men. Utilizing a randomized placebo-controlled parallel-group design, we assigned 21 healthy men to 4 weeks daily inhalation of terbutaline (TER; 4 mg × day-1 , n = 13) or placebo (PLA, n = 8). Before and after treatments, we assessed subjects' whole-body insulin-stimulated glucose disposal and body composition, and collected vastus lateralis muscle and abdominal adipose tissue biopsies. Glucose infusion rate increased by 27% (95% CI: 80 to 238 mg × min-1 , P = 0.001) in TER, whereas no significant changes occurred in PLA (95% CI: -37 to 195 mg × min-1 , P = 0.154). GLUT4 content in muscle or adipose tissue did not change, nor did hexokinase II content or markers of mitochondrial volume in muscle. Change in lean mass was associated with change in glucose infusion rate in TER (r = 0.59, P = 0.03). Beta2 -agonist treatment in close-to-therapeutic doses may augment whole-body insulin-stimulated glucose disposal in healthy young men and part of the change is likely to be explained by muscle hypertrophy. These findings highlight the therapeutic potential of beta2 -agonists for improving insulin sensitivity. KEY POINTS: While studies in rodents have highlighted beta2 -agonists as a means to augment insulin sensitivity, these studies utilized beta2 -agonists at doses inapplicable to humans. Herein we show that a 4-week treatment period with daily therapeutic inhalation of beta2 -agonist increases insulin-stimulated whole-body glucose disposal in young healthy lean men. This effect was associated with an increase of lean mass but not with changes in GLUT4 and hexokinase II or basal glycogen content in skeletal muscle nor GLUT4 content in abdominal adipose tissue. These findings suggest that the enhanced insulin-stimulated whole-body glucose disposal induced by a period of beta2 -agonist treatment in humans, at least in part, is attributed to muscle hypertrophy. Our observations extend findings in rodents and highlight the therapeutic potential of beta2 -agonists to enhance the capacity for glucose disposal and whole-body insulin sensitivity, providing important knowledge with potential application in insulin resistance.

Salbutamol Increases Leg Glucose Uptake and Metabolic Rate but not Muscle Glycogen Resynthesis in Recovery From Exercise.

CONTEXT: Exercise blunts the effect of beta2-agonists on peripheral glucose uptake and energy expenditure. Whether such attenuation extends into recovery is unknown. OBJECTIVE: To examine the effect of a beta2-agonist on leg glucose uptake and metabolic rate in recovery from exercise. METHODS: Using leg arteriovenous balance technique and analyses of thigh muscle biopsies, we investigated the effect of a beta2-agonist (24 mg of oral salbutamol) vs placebo on leg glucose, lactate, and oxygen exchange before and during quadriceps exercise, and 0.5 to 5 hours in recovery from quadriceps exercise, as well as on muscle glycogen resynthesis and activity in recovery. Twelve healthy, lean, young men participated. RESULTS: Before exercise, leg glucose uptake was 0.42 ±â€…0.12 and 0.20 ±â€…0.02 mmol × min-1 (mean ±â€…SD) for salbutamol and placebo (P = .06), respectively, while leg oxygen consumption was around 2-fold higher (P < .01) for salbutamol than for placebo (25 ±â€…3 vs 14 ±â€…1 mL × min-1). No treatment differences were observed in leg glucose uptake, lactate release, and oxygen consumption during exercise. But in recovery, cumulated leg glucose uptake, lactate release, and oxygen consumption was 21 mmol (95% CI 18-24, P = .018), 19 mmol (95% CI 16-23, P < .01), and 1.8 L (95% CI 1.6-2.0, P < .01) higher for salbutamol than for placebo, respectively. Muscle glycogen content was around 30% lower (P < .01) for salbutamol than for placebo in recovery, whereas no treatment differences were observed in muscle glycogen resynthesis or glycogen synthase activity. CONCLUSION: Exercise blunts the effect of beta2-agonist salbutamol on leg glucose uptake, but this attenuation diminishes in recovery. Salbutamol increases leg lactate release in recovery, which may relate to glycolytic trafficking due to excessive myocellular glucose uptake.

Redox balance in human skeletal muscle-derived endothelial cells - Effect of exercise training.

Aerobic training can improve vascular endothelial function in-vivo. The aim of this study was to elucidate the mechanisms underlying this improvement in isolated human microvascular endothelial cells. Sedentary males, aged 57 ± 6 years completed 8 weeks of intense aerobic training. Resting muscle biopsies were obtained from the thigh muscle and used for isolation of endothelial cells (pre n = 23, post n = 16). The cells were analyzed for mitochondrial respiration, H2O2 emission, glycolysis, protein levels of antioxidants, NADPH oxidase, endothelial nitric oxide (NO) synthase and prostacyclin synthase (PGI2S). In-vivo microvascular function, assessed by acetylcholine infusion and arterial blood pressure were also determined. Endothelial mitochondrial respiration and H2O2 formation were similar before and after training whereas the expression of superoxide dismutase and the expression of glutathione peroxidase were 2.4-fold (p = 0.012) and 2.3-fold (p = 0.006) higher, respectively, after training. In-vivo microvascular function was increased by 1.4-fold (p = 0.036) in parallel with a 2.1-fold increase in endothelial PGI2S expression (p = 0.041). Endothelial cell glycolysis was reduced after training, as indicated by a 65% lower basal production of lactate (p = 0.003) and a 30% lower expression of phosphofructokinase (p = 0.011). Subdivision of the participants according to blood pressure at base-line (n = 23), revealed a 2-fold higher (p = 0.049) rate of H2O2 production in endothelial cells from hypertensive participants. Our data show that exercise training increases skeletal muscle microvascular endothelial cell metabolism, antioxidant capacity and the capacity to form prostacyclin. Moreover, elevated blood pressure is associated with increased endothelial mitochondrial ROS formation.