The Rho guanine dissociation inhibitor α inhibits skeletal muscle Rac1 activity and insulin action.

The molecular events governing skeletal muscle glucose uptake have pharmacological potential for managing insulin resistance in conditions such as obesity, diabetes, and cancer. With no current pharmacological treatments to target skeletal muscle insulin sensitivity, there is an unmet need to identify the molecular mechanisms that control insulin sensitivity in skeletal muscle. Here, the Rho guanine dissociation inhibitor α (RhoGDIα) is identified as a point of control in the regulation of insulin sensitivity. In skeletal muscle cells, RhoGDIα interacted with, and thereby inhibited, the Rho GTPase Rac1. In response to insulin, RhoGDIα was phosphorylated at S101 and Rac1 dissociated from RhoGDIα to facilitate skeletal muscle GLUT4 translocation. Accordingly, siRNA-mediated RhoGDIα depletion increased Rac1 activity and elevated GLUT4 translocation. Consistent with RhoGDIα's inhibitory effect, rAAV-mediated RhoGDIα overexpression in mouse muscle decreased insulin-stimulated glucose uptake and was detrimental to whole-body glucose tolerance. Aligning with RhoGDIα's negative role in insulin sensitivity, RhoGDIα protein content was elevated in skeletal muscle from insulin-resistant patients with type 2 diabetes. These data identify RhoGDIα as a clinically relevant controller of skeletal muscle insulin sensitivity and whole-body glucose homeostasis, mechanistically by modulating Rac1 activity.

RNA-bound PGC-1α controls gene expression in liquid-like nuclear condensates.

Plasticity of cells, tissues, and organs is controlled by the coordinated transcription of biological programs. However, the mechanisms orchestrating such context-specific transcriptional networks mediated by the dynamic interplay of transcription factors and coregulators are poorly understood. The peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) is a prototypical master regulator of adaptive transcription in various cell types. We now uncovered a central function of the C-terminal domain of PGC-1α to bind RNAs and assemble multiprotein complexes including proteins that control gene transcription and RNA processing. These interactions are important for PGC-1α recruitment to chromatin in transcriptionally active liquid-like nuclear condensates. Notably, such a compartmentalization of active transcription mediated by liquid-liquid phase separation was observed in mouse and human skeletal muscle, revealing a mechanism by which PGC-1α regulates complex transcriptional networks. These findings provide a broad conceptual framework for context-dependent transcriptional control of phenotypic adaptations in metabolically active tissues.

AXIN1 knockout does not alter AMPK/mTORC1 regulation and glucose metabolism in mouse skeletal muscle.

KEY POINTS: Tamoxifen-inducible skeletal muscle-specific AXIN1 knockout (AXIN1 imKO) in mouse does not affect whole-body energy substrate metabolism. AXIN1 imKO does not affect AICAR or insulin-stimulated glucose uptake in adult skeletal muscle. AXIN1 imKO does not affect adult skeletal muscle AMPK or mTORC1 signalling during AICAR/insulin/amino acid incubation, contraction and exercise. During exercise, α2/ß2/γ3AMPK and AMP/ATP ratio show greater increases in AXIN1 imKO than wild-type in gastrocnemius muscle. ABSTRACT: AXIN1 is a scaffold protein known to interact with >20 proteins in signal transduction pathways regulating cellular development and function. Recently, AXIN1 was proposed to assemble a protein complex essential to catabolic-anabolic transition by coordinating AMPK activation and inactivation of mTORC1 and to regulate glucose uptake-stimulation by both AMPK and insulin. To investigate whether AXIN1 is permissive for adult skeletal muscle function, a phenotypic in vivo and ex vivo characterization of tamoxifen-inducible skeletal muscle-specific AXIN1 knockout (AXIN1 imKO) mice was conducted. AXIN1 imKO did not influence AMPK/mTORC1 signalling or glucose uptake stimulation at rest or in response to different exercise/contraction protocols, pharmacological AMPK activation, insulin or amino acids stimulation. The only genotypic difference observed was in exercising gastrocnemius muscle, where AXIN1 imKO displayed elevated α2/ß2/γ3 AMPK activity and AMP/ATP ratio compared to wild-type mice. Our work shows that AXIN1 imKO generally does not affect skeletal muscle AMPK/mTORC1 signalling and glucose metabolism, probably due to functional redundancy of its homologue AXIN2.

c-Myc overexpression increases ribosome biogenesis and protein synthesis independent of mTORC1 activation in mouse skeletal muscle.

High-intensity muscle contractions (HiMCs) are known to increase c-Myc expression that is known to stimulate ribosome biogenesis and protein synthesis in most cells. However, although c-Myc mRNA transcription and c-Myc mRNA translation have been shown to be upregulated following resistance exercise concomitantly with increased ribosome biogenesis, this connection has not been tested directly. We investigated the effect of adeno-associated virus (AAV)-mediated c-Myc overexpression, with or without fasting or percutaneous electrical stimulation-induced HiMC, on ribosome biogenesis and protein synthesis in adult mouse skeletal muscles. AAV-mediated overexpression of c-Myc in mouse skeletal muscles for 2 wk increased the DNA polymerase subunit POL1 mRNA, 45S-pre-rRNA, total RNA, and muscle protein synthesis without altering mechanistic target of rapamycin complex 1 (mTORC1) signaling under both ad libitum and fasted conditions. RNA-sequencing (RNA-seq) analyses revealed that c-Myc overexpression mainly regulated ribosome biogenesis-related biological processes. The protein synthesis response to c-Myc overexpression mirrored the response with HiMC. No additional effect of combining c-Myc overexpression and HiMC was observed. Our results suggest that c-Myc overexpression is sufficient to stimulate skeletal muscle ribosome biogenesis and protein synthesis without activation of mTORC1. Therefore, the HiMC-induced increase in c-Myc may contribute to ribosome biogenesis and increased protein synthesis following HiMC.NEW & NOTEWORTHY Resistance exercise is known to increase c-Myc expression, which is known to stimulate ribosome biogenesis and protein synthesis in a variety of cells. However, whether the increase in c-Myc stimulates ribosome biogenesis and protein synthesis in skeletal muscles remains unknown. We found that c-Myc overexpression is sufficient to stimulate skeletal muscle ribosome biogenesis and protein synthesis without activation of mTORC1.

Contraction-regulated mTORC1 and protein synthesis: Influence of AMPK and glycogen.

KEY POINTS: AMP-activated protein kinase (AMPK)-dependent Raptor Ser792 phosphorylation does not influence mechanistic target of rapamycin complex 1 (mTORC1)-S6K1 activation by intense muscle contraction. α2 -AMPK activity-deficient mice have lower contraction-stimulated protein synthesis. Increasing glycogen activates mTORC1-S6K1. Normalizing muscle glycogen content rescues reduced protein synthesis in AMPK-deficient mice. ABSTRACT: The mechansitic target of rapamycin complex 1 (mTORC1)-S6K1 signalling pathway regulates muscle growth-related protein synthesis and is antagonized by AMP-activated protein kinase (AMPK) in multiple cell types. Resistance exercise stimulates skeletal muscle mTORC1-S6K1 and AMPK signalling and post-contraction protein synthesis. Glycogen inhibits AMPK and has been proposed as a pro-anabolic stimulus. The present study aimed to investigate how muscle mTORC1-S6K1 signalling and protein synthesis respond to resistance exercise-mimicking contraction in the absence of AMPK and with glycogen manipulation. Resistance exercise-mimicking unilateral in situ contraction of musculus quadriceps femoris in anaesthetized wild-type and dominant negative α2 AMPK kinase dead transgenic (KD-AMPK) mice, measuring muscle mTORC1 and AMPK signalling immediately (0 h) and 4 h post-contraction, and protein-synthesis at 4 h. Muscle glycogen manipulation by 5 day oral gavage of the glycogen phosphorylase inhibitor CP316819 and sucrose (80 g L-1 ) in the drinking water prior to in situ contraction. The mTORC1-S6K1 and AMPK signalling axes were coactivated immediately post-contraction, despite potent AMPK-dependent Ser792 phosphorylation on the mTORC1 subunit raptor. KD-AMPK muscles displayed normal mTORC1-S6K1 activation at 0 h and 4 h post-exercise, although there was impaired contraction-stimulated protein synthesis 4 h post-contraction. Pharmacological/dietary elevation of muscle glycogen content augmented contraction-stimulated mTORC1-S6K1-S6 signalling and rescued the reduced protein synthesis-response in KD-AMPK to wild-type levels. mTORC-S6K1 signalling is not influenced by α2 -AMPK during or after intense muscle contraction. Elevated glycogen augments mTORC1-S6K1 signalling. α2 -AMPK-deficient KD-AMPK mice display impaired contraction-induced muscle protein synthesis, which can be rescued by normalizing muscle glycogen content.

The ULK1/2 and AMPK Inhibitor SBI-0206965 Blocks AICAR and Insulin-Stimulated Glucose Transport.

The small molecule kinase inhibitor SBI-0206965 was originally described as a specific inhibitor of ULK1/2. More recently, it was reported to effectively inhibit AMPK and several studies now report its use as an AMPK inhibitor. Currently, we investigated the specificity of SBI-0206965 in incubated mouse skeletal muscle, measuring the effect on analog 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR)-stimulated AMPK-dependent glucose transport and insulin-stimulated AMPK-independent glucose uptake. Pre-treatment with 10 µM SBI-0206965 for 50 min potently suppressed AICAR-stimulated glucose transport in both the extensor digitorum longus (EDL) and soleus muscle. This was despite only a modest lowering of AICAR-stimulated AMPK activation measured as ACC2 Ser212, while ULK1/2 Ser555 phosphorylation was prevented. Insulin-stimulated glucose transport was also potently inhibited by SBI-0206965 in soleus. No major changes were observed on insulin-stimulated cell signaling. No general effect of SBI-0206965 on intracellular membrane morphology was observed by transmission electron microscopy. As insulin is known to neither activate AMPK nor require AMPK to stimulate glucose transport, and insulin inhibits ULK1/2 activity, these data strongly suggest that SBI-0206965 has a non-specific off-target inhibitory effect on muscle glucose transport. Thus, SBI-0206965 is not a specific inhibitor of the AMPK/ULK-signaling axis in skeletal muscle, and data generated with this inhibitor must be interpreted with caution.

Electroporated GLUT4-7myc-GFP detects in vivo glucose transporter 4 translocation in skeletal muscle without discernible changes in GFP patterns.

NEW FINDINGS: What is the central question of this study? Resolving the mechanism(s) leading to glucose transporter 4 (GLUT4) translocation to the muscle surface membrane has great therapeutic potential. However, the measurement of GLUT4 translocation is technically challenging. Here, we asked whether electroporation of GLUT4-7myc-GFP into skeletal muscle could be used as a tool to study GLUT4 translocation in vivo. What is the main finding and its importance? By acutely inducing GLUT4-7myc-GFP expression in skeletal muscle, we verified that in vivo exercise and AICAR stimulation increased the GLUT4 presence in the sarcolemma measured as myc signal. Importantly, the increased myc signal in the sarcolemma was not accompanied by major visual changes in the distribution of the GFP signal. ABSTRACT: Insulin and exercise lead to translocation of the glucose transporter 4 (GLUT4) to the surface membrane of skeletal muscle fibres. This process is pivotal for facilitating glucose uptake into skeletal muscle. To study this, a robust assay is needed to measure the translocation of GLUT4 in adult skeletal muscle directly. Here, we aimed to validate a simple GLUT4 translocation assay using a genetically encoded biosensor in mouse skeletal muscle. We transfected GLUT4-7myc-GFP into mouse muscle to study live GLUT4 movement and to evaluate GLUT4 insertion in the muscle surface membrane after in vivo running exercise and pharmacological activation of AMP-activated protein kinase (AMPK). Transfection led to expression of GLUT4-7myc-GFP that was dynamic in live flexor digitorum brevis fibres and which, upon insulin stimulation, exposed the myc epitope extracellularly. Running exercise, in addition to AMPK activation by 5-aminoimidazole-4-carboxamide ribonucleotide, induced ∼125 and ∼100% increase, respectively, in extracellularly exposure of GLUT4 in the surface membrane of tibialis anterior muscle. Interestingly, the clear increase in surface-exposed GLUT4 content induced by insulin, exercise or AMPK activation was not accompanied by any discernible reorganization of the GLUT4-GFP signal. In conclusion, we provide a detailed description of an easy-to-use translocation assay to study GLUT4 accumulation at the surface membrane induced by exercise and exercise-mimicking stimuli. Notably, our analyses revealed that increased GLUT4 surface membrane accumulation was not accompanied by a discernible change in the GLUT4 localization pattern.

ß-Actin shows limited mobility and is required only for supraphysiological insulin-stimulated glucose transport in young adult soleus muscle.

Studies in skeletal muscle cell cultures suggest that the cortical actin cytoskeleton is a major requirement for insulin-stimulated glucose transport, implicating the ß-actin isoform, which in many cell types is the main actin isoform. However, it is not clear that ß-actin plays such a role in mature skeletal muscle. Neither dependency of glucose transport on ß-actin nor actin reorganization upon glucose transport have been tested in mature muscle. To investigate the role of ß-actin in fully differentiated muscle, we performed a detailed characterization of wild type and muscle-specific ß-actin knockout (KO) mice. The effects of the ß-actin KO were subtle; however, we confirmed the previously reported decline in running performance of ß-actin KO mice compared with wild type during repeated maximal running tests. We also found insulin-stimulated glucose transport into incubated muscles reduced in soleus but not in extensor digitorum longus muscle of young adult mice. Contraction-stimulated glucose transport trended toward the same pattern, but the glucose transport phenotype disappeared in soleus muscles from mature adult mice. No genotype-related differences were found in body composition or glucose tolerance or by indirect calorimetry measurements. To evaluate ß-actin mobility in mature muscle, we electroporated green fluorescent protein (GFP)-ß-actin into flexor digitorum brevis muscle fibers and measured fluorescence recovery after photobleaching. GFP-ß-actin showed limited unstimulated mobility and no changes after insulin stimulation. In conclusion, ß-actin is not required for glucose transport regulation in mature mouse muscle under the majority of the tested conditions. Thus, our work reveals fundamental differences in the role of the cortical ß-actin cytoskeleton in mature muscle compared with cell culture.

Altered ROS production, NF-κB activation and interleukin-6 gene expression induced by electrical stimulation in dystrophic mdx skeletal muscle cells.

Duchenne muscular dystrophy is a fatal X-linked genetic disease, caused by mutations in the dystrophin gene, which cause functional loss of this protein. This pathology is associated with an increased production of reactive oxygen (ROS) and nitrogen species. The aim of this work was to study the alterations in NF-κB activation and interleukin-6 (IL-6) expression induced by membrane depolarization in dystrophic mdx myotubes. Membrane depolarization elicited by electrical stimulation increased p65 phosphorylation, NF-κB transcriptional activity and NF-κB-dependent IL-6 expression in wt myotubes, whereas in mdx myotubes it had the opposite effect. We have previously shown that depolarization-induced intracellular Ca2+ increases and ROS production are necessary for NF-κB activation and stimulation of gene expression in wt myotubes. Dystrophic myotubes showed a reduced amplitude and area under the curve of the Ca2+ transient elicited by electrical stimulation. On the other hand, electrical stimuli induced higher ROS production in mdx than wt myotubes, which were blocked by NOX2 inhibitors. Moreover, mRNA expression and protein levels of the NADPH oxidase subunits: p47phox and gp91phox were increased in mdx myotubes. Looking at ROS-dependence of NF-κB activation we found that in wt myotubes external administration of 50 µM H2O2 increased NF-κB activity; after administration of 100 and 200 µM H2O2 there was no effect. In mdx myotubes there was a dose-dependent reduction in NF-κB activity in response to external administration of H2O2, with a significant effect of 100 µM and 200 µM, suggesting that ROS levels are critical for NF-κB activity. Prior blockage with NOX2 inhibitors blunted the effects of electrical stimuli in both NF-κB activation and IL-6 expression. Finally, to ascertain whether stimulation of NF-κB and IL-6 gene expression by the inflammatory pathway is also impaired in mdx myotubes, we studied the effect of lipopolysaccharide on both NF-κB activation and IL-6 expression. Exposure to lipopolysaccharide induced a dramatic increase in both NF-κB activation and IL-6 expression in both wt and mdx myotubes, suggesting that the altered IL-6 gene expression after electrical stimulation in mdx muscle cells is due to dysregulation of Ca2+ release and ROS production, both of which impinge on NF-κB signaling. IL-6 is a key metabolic modulator that is released by the skeletal muscle to coordinate a multi-systemic response (liver, muscle, and adipocytes) during physical exercise; the alteration of this response in dystrophic muscles may contribute to an abnormal response to contraction and exercise.

Effects of plyometric training on maximal-intensity exercise and endurance in male and female soccer players.

In a randomised controlled trial design, effects of 6 weeks of plyometric training on maximal-intensity exercise and endurance performance were compared in male and female soccer players. Young (age 21.1 ± 2.7 years) players with similar training load and competitive background were assigned to training (women, n = 19; men, n = 21) and control (women, n = 19; men, n = 21) groups. Players were evaluated for lower- and upper-body maximal-intensity exercise, 30 m sprint, change of direction speed and endurance performance before and after 6 weeks of training. After intervention, the control groups did not change, whereas both training groups improved jumps (effect size (ES) = 0.35-1.76), throwing (ES = 0.62-0.78), sprint (ES = 0.86-1.44), change of direction speed (ES = 0.46-0.85) and endurance performance (ES = 0.42-0.62). There were no differences in performance improvements between the plyometric training groups. Both plyometric groups improved more in all performance tests than the controls. The results suggest that adaptations to plyometric training do not differ between men and women.

Effect of unilateral, bilateral, and combined plyometric training on explosive and endurance performance of young soccer players.

The aim of the study was to compare the effects of bilateral, unilateral, or combined bilateral and unilateral plyometric training (PT) on muscle power output, endurance, and balance performance adaptations in young soccer players. Four groups of young soccer players (age 11.4 ± 2.2 years) were divided into control group (CG; n = 14), bilateral group (BG; n = 12), unilateral group (UG; n = 16), and bilateral + unilateral group (B + UG; n = 12). Players were measured in unilateral and bilateral countermovement jump with arms, 5 multiple bounds test, 20-cm drop jump reactive strength index, maximal kicking velocity, sprint and agility test time, endurance, and balance performance. The PT was applied during 6 weeks, 2 sessions per week, for a total of 2,160 jumps. After intervention, all PT groups showed a statistically significant (p ≤ 0.05) change in all performance measures, with no statistically significant differences between treatments. Among the 21 performance measures, the B + UG showed a significantly (p ≤ 0.05) higher performance change in 13 of them vs. the CG, whereas the UG and BG showed only 6 and 3, respectively. The current study showed that bilateral, unilateral, and combined bilateral and unilateral PT ensured significant improvement in several muscular power and endurance performance measures in young soccer players. However, the combination of unilateral and bilateral drills seems more advantageous to induce superior performance improvements.

Effect of Vertical, Horizontal, and Combined Plyometric Training on Explosive, Balance, and Endurance Performance of Young Soccer Players.

The aim of this study was to compare the effects of 6 weeks of vertical, horizontal, or combined vertical and horizontal plyometric training on muscle explosive, endurance, and balance performance. Forty young soccer players aged between 10 and 14 years were randomly divided into control (CG; n = 10), vertical plyometric group (VG; n = 10), horizontal plyometric group (HG; n = 10), and combined vertical and horizontal plyometric group (VHG; n = 10). Players performance in the vertical and horizontal countermovement jump with arms, 5 multiple bounds test (MB5), 20-cm drop jump reactive strength index (RSI20), maximal kicking velocity (MKV), sprint, change of direction speed (CODS), Yo-Yo intermittent recovery level 1 test (Yo-Yo IR1), and balance was measured. No significant or meaningful changes in the CG, apart from small change in the Yo-Yo IR1, were observed while all training programs resulted in meaningful changes in explosive, endurance, and balance performance. However, only VHG showed a statistically significant (p ≤ 0.05) increase in all performance test and most meaningful training effect difference with the CG across tests. Although no significant differences in performance changes were observed between experimental groups, the VHG program was more effective compared with VG (i.e., jumps, MKV, sprint, CODS, and balance performance) and HG (i.e., sprint, CODS, and balance performance) to small effect. The study demonstrated that vertical, horizontal, and combined vertical and horizontal jumps induced meaningful improvement in explosive actions, balance, and intermittent endurance capacity. However, combining vertical and horizontal drills seems more advantageous to induce greater performance improvements.

Effect of Progressive Volume-Based Overload During Plyometric Training on Explosive and Endurance Performance in Young Soccer Players.

The purpose of the study was to compare the effects of progressive volume-based overload with constant volume-based overload on muscle explosive and endurance performance adaptations during a biweekly short-term (i.e., 6 weeks) plyometric training intervention in young soccer players. Three groups of young soccer players (age 13.0 ± 2.3 years) were divided into: control (CG; n = 8) and plyometric training with (PPT; n = 8) and without (NPPT; n = 8) a progressive increase in volume (i.e., 16 jumps per leg per week, with an initial volume of 80 jumps per leg each session). Bilateral and unilateral horizontal and vertical countermovement jump with arms (CMJA), 20-cm drop jump reactive strength index (RSI20), maximal kicking velocity (MKV), 10-m sprint, change of direction speed (CODS), and Yo-Yo intermittent recovery level 1 test (Yo-Yo IR1) were measured. Although both experimental groups significantly increased CMJA, RSI20, CODS, and endurance performance, only PPT showed a significant improvement in MKV and 10-m sprint time. In addition, only PPT showed a significantly higher performance improvement in jumping, MKV, and Yo-Yo IR1 compared with CG. Also, PPT showed higher meaningful improvement compared with NPPT in all (except 1) jump performance measures. Furthermore, although PPT involved a higher total volume compared with NPPT, training efficiency (i.e., percentage change in performance/total jump volume) was similar between groups. Our results show that PPT and NPPT ensured significant improvement in muscle explosive and endurance performance measures. However, a progressive increase in plyometric training volume seems more advantageous to induce soccer-specific performance improvements.

The effects of interday rest on adaptation to 6 weeks of plyometric training in young soccer players.

The purpose of this study was to determine the effects of short-term plyometric training interposed with 24 or 48 hours of rest between training sessions on explosive and endurance adaptations in young soccer players. A total of 166 players, between 10 and 17 years of age, were randomly divided into 3 groups: a control group (CG; n = 55) and 2 plyometric training groups with 24 hours (PT24; n = 54) and 48 hours (PT48; n = 57) of rest between training sessions. Before and after intervention, players were measured in squat jump, countermovement jump, 20 (RSI20) cm drop jump reactive strength index, broad long jump, 20-m sprint time, 10 × 5-m agility time, 20-m multistage shuttle run test, and sit-and-reach test. The plyometric training program was applied during 6 weeks, 2 sessions per week, with a load from 140 to 260 jumps per session, replacing some soccer-specific drills. After intervention, the CG did not show significant performance changes. PT24 and PT48 groups showed a small-to-moderate significant improvement in all performance tests (p < 0.001), with no differences between treatments. Although it has been recommended that plyometric drills should not be conducted on consecutive days, the study shows that plyometric training applied twice weekly on consecutive or nonconsecutive days results in similar explosive and endurance adaptations in young male soccer players.

Effects of plyometric training on endurance and explosive strength performance in competitive middle- and long-distance runners.

The purpose of this study was to examine the effect of a short-term plyometric training program on explosive strength and endurance performance in highly competitive middle- and long-distance runners. Athletes were randomly assigned to a control group (CG, n = 18, 12 men) and an explosive strength training group (TG, n = 18, 10 men). Drop jump (DJ) from 20 (DJ20) and 40 cm (DJ40), countermovement jump with arms (CMJA), 20-m sprint time, and 2.4-km endurance run time test were carried out before and after 6 weeks of explosive strength training. Also, the combined standardized performance (CSP) in the endurance and explosive strength test was analyzed. After intervention, the CG did not show any significant change in performance, whereas the TG showed a significant reduction in 2.4-km endurance run time (-3.9%) and 20-m sprint time (-2.3%) and an increase in CMJA (+8.9%), DJ20 (+12.7%), and DJ40 (16.7%) explosive performance. Strength training group also exhibited a significant increase in CSP, although the CG showed significant reduction. We conclude that properly programmed concurrent explosive strength and endurance training could be advantageous for middle- and long-distance runners in their competitive performance, especially in events characterized by sprinting actions with small time differences at the end of the race.

Effects of in-season low-volume high-intensity plyometric training on explosive actions and endurance of young soccer players.

Integrating specific training methods to improve explosive actions and endurance in youth soccer is an essential part of players' development. This study investigated the efficiency of short-term vertical plyometric training program within soccer practice to improve both explosive actions and endurance in young soccer players. Seventy-six players were recruited and assigned either to a training group (TG; n = 38; 13.2 ± 1.8 years) or a control group (CG; n = 38; 13.2 ± 1.8 years) group. All players trained twice per week, but the TG followed a 7-week plyometric program implemented within soccer practice, whereas the CG followed regular practice. Twenty-meter sprint time (20-m), Illinois agility test time, countermovement jump (CMJ) height, 20- (RSI20) and 40- (RSI40) cm drop jump reactive strength index, multiple 5 bounds distance (MB5), maximal kicking test for distance (MKD), and 2.4-km time trial were measured before and after the 7-week period. Plyometric training induced significant (p ≤ 0.05) and small to moderate standardized effect (SE) improvement in the CMJ (4.3%; SE = 0.20), RSI20 (22%; SE = 0.57), RSI40 (16%; SE = 0.37), MB5 (4.1%; SE = 0.28), Illinois agility test time (-3.5%, SE = -0.26), MKD (14%; SE = 0.53), 2.4-km time trial (-1.9%; SE = -0.27) performances but had a trivial and nonsignificant effect on 20-m sprint time (-0.4%; SE = -0.03). No significant improvements were found in the CG. An integrated vertical plyometric program within the regular soccer practice can substitute soccer drills to improve most explosive actions and endurance, but horizontal exercises should also be included to enhance sprinting performance.

[Eight weeks of combined high intensity intermittent exercise normalized altered metabolic parameters in women]. / ¿Pueden ocho semanas de ejercicio físico combinado normalizar marcadores metabólicos de sujetos hiperglicémicos y dislipidémicos?

BACKGROUND: Short term physical training programs may improve insulin resistance and hyperglycemia. AIM: To assess the effects of eight weeks of combined exercise program on serum lipids and glycemic level in women with hyperglycemia and hypercholesterolemia. PATIENTS AND METHODS: Ten healthy women, nine women with hyperglycemia, ten with hypercholesterolemia and nine with hyperglycemia/hypercholesterolemia were studied. Participants were subjected to eight weeks into a program of combined physical exercise (high intensity interval + resistance training). RESULTS: Fasting glycemia decreased by 12 and 14% in hyperglycemic and hyperglycemic/hypercholesterolemic participants, respectively. Serum insulin decreased in all groups in a range from 27 to 37%. HOMA IR for insulin resistance decreased similarly. A significant decrease in TC and TG was observed only in those altered baseline subjects. CONCLUSIONS: Eight weeks of combined physical exercise had a favorable effect on insulin resistance in this group of women.

The effects of interset rest on adaptation to 7 weeks of explosive training in young soccer players.

The aim of the study was to compare the effects of plyometric training using 30, 60, or 120 s of rest between sets on explosive adaptations in young soccer players. Four groups of athletes (age 10.4 ± 2.3 y; soccer experience 3.3 ± 1.5 y) were randomly formed: control (CG; n = 15), plyometric training with 30 s (G30; n = 13), 60 s (G60; n = 14), and 120 s (G120; n = 12) of rest between training sets. Before and after intervention players were measured in jump ability, 20-m sprint time, change of direction speed (CODS), and kicking performance. The training program was applied during 7 weeks, 2 sessions per week, for a total of 840 jumps. After intervention the G30, G60 and G120 groups showed a significant (p = 0.0001 - 0.04) and small to moderate effect size (ES) improvement in the countermovement jump (ES = 0.49; 0.58; 0.55), 20 cm drop jump reactive strength index (ES = 0.81; 0.89; 0.86), CODS (ES = -1.03; -0.87; -1.04), and kicking performance (ES = 0.39; 0.49; 0.43), with no differences between treatments. The study shows that 30, 60, and 120 s of rest between sets ensure similar significant and small to moderate ES improvement in jump, CODS, and kicking performance during high-intensity short-term explosive training in young male soccer players. Key pointsReplacing some soccer drills by low volume high-intensity plyometric training would be beneficial in jumping, change of direction speed, and kicking ability in young soccer players.A rest period of 30, 60 or 120 seconds between low-volume high-intensity plyometric sets would induce significant and similar explosive adaptations during a short-term training period in young soccer players.Data from this research can be helpful for soccer trainers in choosing efficient drills and characteristics of between sets recovery programs to enhance performances in young male soccer players.

Unresolved questions in the regulation of skeletal muscle insulin action by reactive oxygen species.

Reactive oxygen species (ROS) are well-established signaling molecules implicated in a wide range of cellular processes, including both oxidative stress and intracellular redox signaling. In the context of insulin action within its target tissues, ROS have been reported to exert both positive and negative regulatory effects. However, the precise molecular mechanisms underlying this duality remain unclear. This Review examines the complex role of ROS in insulin action, with a particular focus on skeletal muscle. We aim to address three critical aspects: (a) the proposed intracellular pro-oxidative redox shift elicited by insulin, (b) the evidence supporting that redox-sensitive cysteine modifications impact insulin signaling and action, and (c) cellular mechanisms underlying how ROS can paradoxically act as both enhancers and inhibitors of insulin action. This Review underscores the urgent need for more systematic research to identify specific reactive species, redox targets, and the physiological significance of redox signaling in maintaining insulin action and metabolic health, with a particular emphasis on human skeletal muscle.