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In this study, we evaluated the effects of a novel pedal design, characterized by a downward and forward shift of the cleat fixing platform relative to the pedal axle, on maximal power output and mechanical efficiency in 22 well-trained cyclists. Maximal power output was measured during a series of short (5-s) intermittent sprints on an isokinetic cycle ergometer at cadences from 40 to 120 rev min(-1). Mechanical efficiency was evaluated during a submaximal incremental exercise test on a bicycle ergometer using continuous VO(2) and VCO(2) measurement. Similar tests with conventional pedals and the novel pedals, which were mounted on the individual racing bike of the participant, were randomized. Maximal power was greater with novel pedals than with conventional pedals (between 6.0%, s(x) = 1.5 at 40 rev min(-1) and 1.8%, s(x) = 0.7 at 120 rev min(-1); P = 0.01). Torque production between crank angles of 60 degrees and 150 degrees was higher with novel pedals than with conventional pedals (P = 0.004). The novel pedal design did not affect whole-body VO(2) or VCO(2). Mechanical efficiency was greater with novel pedals than with conventional pedals (27.2%, s(x) = 0.9 and 25.1%, s(x) = 0.9% respectively; P = 0.047; effect size = 0.9). In conclusion, the novel pedals can increase maximal power output and mechanical efficiency in well-trained cyclists.

In myogenic C2C12cells, 5 mM creatine increased the incorporation of labeled [35S]methionine into sarcoplasmic (+20%, P < 0.05) and myofibrillar proteins (+50%, P < 0.01). Creatine also promoted the fusion of myoblasts assessed by an increased number of nuclei incorporated within myotubes (+40%, P < 0.001). Expression of myosin heavy chain type II (+1,300%, P < 0.001), troponin T (+65%, P < 0.01), and titin (+40%, P < 0.05) was enhanced by creatine. Mannitol, taurine, and β-alanine did not mimic the effect of creatine, ruling out an osmolarity-dependent mechanism. The addition of rapamycin, the inhibitor of mammalian target of rapamycin/70-kDa ribosomal S6 protein kinase (mTOR/p70s6k) pathway, and SB 202190, the inhibitor of p38, completely blocked differentiation in control cells, and creatine did not reverse this inhibition, suggesting that the mTOR/p70s6kand p38 pathways could be potentially involved in the effect induced by creatine on differentiation. Creatine upregulated phosphorylation of protein kinase B (Akt/PKB; +60%, P < 0.001), glycogen synthase kinase-3 (+70%, P < 0.001), and p70s6k(+50%, P < 0.001). Creatine also affected the phosphorylation state of p38 (−50% at 24 h and +70% at 96 h, P < 0.05) as well as the nuclear content of its downstream targets myocyte enhancer factor-2 (−55% at 48 h and +170% at 96 h, P < 0.05) and MyoD (+60%, P < 0.01). In conclusion, this study points out the involvement of the p38 and the Akt/PKB-p70s6kpathways in the enhanced differentiation induced by creatine in C2C12cells.

The study compared the net decline of intramyocellular lipids (IMCL) during exercise (n = 18) measured by biochemical assay (BIO) and Oil Red O (ORO) staining on biopsy samples from vastus lateralis muscle and by (1)H-MR spectroscopy (MRS) sampled in an 11 x 11 x 18-mm(3) voxel in the same muscle. IMCL was measured before and after a 2-h cycling bout ( approximately 75% Vo(2 peak)). ORO and MRS measurements showed substantial IMCL use during exercise of 31 +/- 12 and 47 +/- 6% of preexercise IMCL content. In contrast, use of BIO for IMCL determination did not reveal an exercise-induced breakdown of IMCL (2 +/- 9%, P = 0.29) in young healthy males. Correlations between different measures of exercise-induced IMCL degradation were low. Coefficients were 0.48 for MRS vs. ORO (P = 0.07) and were even lower for BIO vs. MRS (r = 0.38, P = 0.13) or ORO (r = 0.08, P = 0.78). This study demonstrates that different methods to measure IMCL in human muscles can result in different conclusions with regard to exercise-induced IMCL changes. MRS has the advantage that it is noninvasive, however, not fiber type specific and hampered by an at least 30-min delay in measurements after exercise completion and may overestimate IMCL use. BIO is the only quantitative method but is subject to variation when biopsies have different fiber type composition. However, BIO yields lower IMCL breakdown compared with ORO and MRS. ORO has the major advantage that it is fiber type specific, and it therefore provides information that is not available with the other methods. ispartof: American Journal of Physiology: Endocrinology and Metabolism vol:293 issue:1 pages:E428-E434 ispartof: location:United States status: published

DERAVE, WIM, ANN MERTENS, ERIK MULS, KAREL PARDAENS, AND PETER HESPEL. Effects of postabsorptive and postprandial exercise on glucoregulation in metabolic syndrome. Obesity. 2007;15:704 –711. Objective: The aim of this study was to investigate the effects of an acute exercise bout in the morning in the post-absorptive or postprandial state on the glycemic and insulinemic response to three standardized meals throughout the day. It is hypothesized that post-absorptive exercise enhances fat oxidation rate during exercise and thereafter attenuates the glucose and insulin response to subsequent meals. Research Methods and Procedures: Seven sedentary males with metabolic syndrome (age, 45 11 years; BMI, 34 3 kg/m 2 ) were studied in a crossover design comparing three conditions: no exercise, postprandial and post-absorptive exercise (at 60% of the individual V u O2max for 45 minutes). Substrate use was evaluated by indirect calorimetry during exercise. Venous blood samples were taken at regular (30- to 60-minute) intervals throughout the day, and glucose, insulin, and triglyceride concentrations were determined. Results: During exercise, a higher fat oxidation rate was observed in the post-absorptive than the postprandial state. The glycemic response to a standardized high-carbohydrate breakfast was lower when exercising after breakfast than when exercising before breakfast. There was no effect of either exercise mode on glucose and insulin response to lunch and supper. Discussion: Post-absorptive exercise has the advantage of promoting fat use, whereas postprandial exercise can attenuate the glycemic response to breakfast. Neither exercise mode acutely induces improved glucoregulation later during the day. The impact of meal timing on the effects of regular exercise training on glycemic control in this population remains to be studied.

There is growing in vivo evidence that the dipeptide carnosine has protective effects in metabolic diseases. A critical unanswered question is whether its site of action is tissues or plasma. This was investigated using oral carnosine versus β-alanine supplementation in a high-fat diet rat model. Thirty-six male Sprague–Dawley rats received a control diet (CON), a high-fat diet (HF; 60% of energy from fat), the HF diet with 1.8% carnosine (HFcar), or the HF diet with 1% β-alanine (HFba), as β-alanine can increase muscle carnosine without increasing plasma carnosine. Insulin sensitivity, inflammatory signaling, and lipoxidative stress were determined in skeletal muscle and blood. In a pilot study, urine was collected. The 3 HF groups were significantly heavier than the CON group. Muscle carnosine concentrations increased equally in the HFcar and HFba groups, while elevated plasma carnosine levels and carnosine–4-hydroxy-2-nonenal adducts were detected only in the HFcar group. Elevated plasma and urine Nε-(carboxymethyl)lysine in HF rats was reduced by ∼50% in the HFcar group but not in the HFba group. Likewise, inducible nitric oxide synthase mRNA was decreased by 47% (p < 0.05) in the HFcar group, but not in the HFba group, compared with HF rats. We conclude that plasma carnosine, but not muscle carnosine, is involved in preventing early-stage lipoxidation in the circulation and inflammatory signaling in the muscle of rats.

High rate of muscular oxygen utilization facilitates the development of hypoxemia during exercise at altitude. Because endurance training stimulates oxygen extraction capacity, we investigated whether endurance athletes are at higher risk to developing hypoxemia and thereby acute mountain sickness symptoms during exercise at simulated high altitude. Elite athletes (ATL; n = 8) and fit controls (CON; n = 7) cycled for 20 min at 100 W (EX100W), as well as performed an incremental maximal oxygen consumption test (EXMAX) in normobaric hypoxia (0.107 inspired O2fraction) or normoxia (0.209 inspired O2fraction). Cardiorespiratory responses, arterial Po2(PaO2), and oxygenation status in m. vastus lateralis [tissue oxygenation index (TOIM)] and frontal cortex (TOIC) by near-infrared spectroscopy, were measured. Muscle O2uptake rate was estimated from change in oxyhemoglobin concentration during a 10-min arterial occlusion in m. gastrocnemius. Maximal oxygen consumption in normoxia was 70 ± 2 ml·min−1·kg−1in ATL vs. 43 ± 2 ml·min−1·kg−1in CON, and in hypoxia decreased more in ATL (−41%) than in CON (−25%, P < 0.05). Both in normoxia at PaO2of ∼95 Torr, and in hypoxia at PaO2of ∼35 Torr, muscle O2uptake was twofold higher in ATL than in CON (0.12 vs. 0.06 ml·min−1·100 g−1; P < 0.05). During EX100Win hypoxia, PaO2dropped to lower ( P < 0.05) values in ATL (27.6 ± 0.7 Torr) than in CON (33.5 ± 1.0 Torr). During EXMAX, but not during EX100W, TOIMwas ∼15% lower in ATL than in CON ( P < 0.05). TOICwas similar between the groups at any time. This study shows that maintenance of high muscular oxygen extraction rate at very low circulating PaO2stimulates the development of hypoxemia during submaximal exercise in hypoxia in endurance-trained individuals. This effect may predispose to premature development of acute mountain sickness symptoms during exercise at altitude.

Electrical field stimulation of isolated, incubated rodent skeletal muscles is a frequently used model to study the effects of contractions on muscle metabolism. In this study, this model was used to investigate the effects of electrically stimulated contractions on creatine transport. Soleus and extensor digitorum longus muscles of male NMRI mice (35–50 g) were incubated in an oxygenated Krebs buffer between platinum electrodes. Muscles were exposed to [14C]creatine for 30 min after either 12 min of repeated tetanic isometric contractions (contractions) or electrical stimulation of only the buffer before incubation of the muscle (electrolysis). Electrolysis was also investigated in the presence of the reactive oxygen species (ROS) scavenging enzymes superoxide dismutase (SOD) and catalase. Both contractions and (to a lesser degree) electrolysis stimulated creatine transport severalfold over basal. The amount of electrolysis, but not contractile activity, induced (determined) creatine transport stimulation. Incubation with SOD and catalase at 100 and 200 U/ml decreased electrolysis-induced creatine transport by ∼50 and ∼100%, respectively. The electrolysis effects on creatine uptake were completely inhibited by β-guanidino propionic acid, a competitive inhibitor of (creatine for) the creatine transporter (CRT), and were accompanied by increased cell surface expression of CRT. Muscle glucose transport was not affected by electrolysis. The present results indicate that electrical field stimulation of incubated mouse muscles, independently of contractions per se, stimulates creatine transport by a mechanism that depends on electrolysis-induced formation of ROS in the incubation buffer. The increased creatine uptake is paralleled by an increased cell surface expression of the creatine transporter.

Animal models are valuable research tools towards effective prevention of sarcopenia and towards a better understanding of the mechanisms underlying skeletal muscle aging. We investigated whether senescence-accelerated mouse (SAM) strains provide valid models for skeletal muscle aging studies. Male senescence-prone mice SAMP6 and SAMP8 were studied at age 10, 25 and 60 weeks and compared with senescence-resistant strain, SAMR1. Soleus and EDL muscles were tested for in vitro contractile properties, phosphocreatine content, muscle mass and fiber-type distribution. Declined muscle mass and contractility were observed at 60 weeks, the differences being more pronounced in SAMP8 than SAMP6 and more pronounced in soleus than EDL. Likewise, age-related decreases in muscle phosphocreatine content and type-II fiber size were most pronounced in SAMP8 soleus. In conclusion, typical features of muscular senescence occur at relatively young age in SAMP8 and nearly twice as fast as compared with other models. We suggest that soleus muscles of SAMP8 mice provide a cost-effective model for muscular aging studies.

The effects were compared of exercise in the fasted state and exercise with a high rate of carbohydrate intake on intramyocellular triglyceride (IMTG) and glycogen content of human muscle. Using a randomized crossover study design, nine young healthy volunteers participated in two experimental sessions with an interval of 3 weeks. In each session subjects performed 2 h of constant-load bicycle exercise ( approximately 75% ), followed by 4 h of controlled recovery. On one occasion they exercised after an overnight fast (F), and on the other (CHO) they received carbohydrates before ( approximately 150 g) and during (1 g (kg bw)(-1) h(-1)) exercise. In both conditions, subjects ingested 5 g carbohydrates per kg body weight during recovery. Fibre type-specific relative IMTG content was determined by Oil red O staining in needle biopsies from m. vastus lateralis before, immediately after and 4 h after exercise. During F but not during CHO, the exercise bout decreased IMTG content in type I fibres from 18 +/- 2% to 6 +/- 2% (P = 0.007) area lipid staining. Conversely, during recovery, IMTG in type I fibres decreased from 15 +/- 2% to 10 +/- 2% in CHO, but did not change in F. Neither exercise nor recovery changed IMTG in type IIa fibres in any experimental condition. Exercise-induced net glycogen breakdown was similar in F and CHO. However, compared with CHO (11.0 +/- 7.8 mmol kg(-1) h(-1)), mean rate of postexercise muscle glycogen resynthesis was 3-fold greater in F (32.9 +/- 2.7 mmol kg(-1) h(-1), P = 0.01). Furthermore, oral glucose loading during recovery increased plasma insulin markedly more in F (+46.80 microU ml(-1)) than in CHO (+14.63 microU ml(-1), P = 0.02). We conclude that IMTG breakdown during prolonged submaximal exercise in the fasted state takes place predominantly in type I fibres and that this breakdown is prevented in the CHO-fed state. Furthermore, facilitated glucose-induced insulin secretion may contribute to enhanced muscle glycogen resynthesis following exercise in the fasted state.

Purpose:The purpose of this study was to investigate the effect of acute and 4-week Rhodiola rosea intake on physical capacity, muscle strength, speed of limb movement, reaction time, and attention.Methods:PHASE I: A double blind placebo-controlled randomized study (n = 24) was performed, consisting of 2 sessions (2 days per session). Day 1: One hour after acute Rhodiola rosea intake (R, 200-mg Rhodiola rosea extract containing 3% rosavin + 1% salidroside plus 500 mg starch) or placebo (P, 700 mg starch) speed of limb movement (plate tapping test), aural and visual reaction time, and the ability to sustain attention (Fepsy Vigilance test) were assessed. Day 2: Following the same intake procedure as on day 1, maximal isometric knee-extension torque and endurance exercise capacity were tested. Following a 5-day washout period, the experimental procedure was repeated, with the treatment regimens being switched between groups (session 2). PHASE II: A double blind placebo-controlled study (n = 12) was performed. Subjects underwent sessions 3 and 4, identical to Phase I, separated by a 4-week R/P intake, during which subjects ingested 200 mg R/P per day.Results:PHASE I: Compared with P, acute R intake in Phase I increased 0 < -05) time to exhaustion from 16.8 ± 0.7 min to 17.2 ± 0.8 min. Accordingly, VO2peak (p < .05) and VCO2peak(p< .05) increased during R compared to P from 50.9 ± 1.8 ml • min-1 • kg−1 to 52.9 ± 2.7 ml • min-1 • kg"’ (VO2peak) and from 60.0 ± 2.3 ml • min-1 • kg-’ to 63.5 ± 2.7 ml • min-1 kg-1 (VCO2peak). Pulmonary ventilation (p = .07) tended to increase more during R than during P(P: 115.9±7.7L/min; R: 124.8 ± 7.7 L/min). All other parameters remained unchanged. PHASE II: Four-week R intake did not alter any of the variables measured.Conclusion:Acute Rhodiola rosea intake can improve endurance exercise capacity in young healthy volunteers. This response was not altered by prior daily 4-week Rhodiola intake.

The impact of air ventilation on performance and physiological responses during stationary exercise in the laboratory was studied. Fourteen well-trained cyclists performed three exercise tests on a cycle ergometer, each separated by a 1-week interval. The first test was a graded test to determine the power output corresponding with the 4-mmol l(-1) lactate level. Tests 2 and 3 were 30-min constant-load tests at a power output corresponding with this 4-mmol l(-1) lactate threshold. One constant-load test was performed in the absence (NAV), whilst the other was performed in the presence (AV) of air ventilation (3 m s(-1)). During the constant-load tests, heart rate, tympanic temperature, blood lactate concentration and oxygen uptake (VO2) were measured at 10-min intervals and at the end of the test. Differences between the two test conditions were evaluated using paired t-tests. During NAV, 12 subjects interrupted the test due to premature exhaustion (exercise duration30 min), versus only seven in AV ( P0.05). At the end of the test tympanic temperature was 35.9 (0.2) degrees C in AV and was higher in NAV [36.7 (0.2) degrees C, P0.05]. Exercise heart rate increased at a faster rate during NAV [+2.2 (0.3) beats min(-1)] than during AV [+1.5 (0.2) beats min(-1), P0.05]. Blood lactate concentration and VO2 were similar between conditions. Air ventilation is essential to prevent an upward shift in the lactate:heart rate as well as the power output:heart rate relationship during laboratory exercise testing and indoor exercise training.

The present study was undertaken to explore the effects of creatine and creatine plus protein supplementation on GLUT-4 and glycogen content of human skeletal muscle. This was investigated in muscles undergoing a decrease (immobilization) and subsequent increase (resistance training) in activity level, compared with muscles with unaltered activity pattern. A double-blind, placebo-controlled trial was performed by 33 young healthy subjects. The subjects′ right legs were immobilized with a cast for 2 wk, followed by a 6-wk resistance training program for the right knee extensor muscles. The participants were supplemented throughout the study with either placebo (Pl group) or creatine (Cr group) or with creatine during immobilization and creatine plus protein during retraining (Cr+P group). Needle biopsies were bilaterally taken from the vastus lateralis. GLUT-4 protein expression was reduced by the immobilization in all groups ( P < 0.05). During retraining, GLUT-4 content increased ( P < 0.05) in both Cr (+24%) and Cr+P (+33%), which resulted in higher posttraining GLUT-4 expression compared with Pl ( P < 0.05). Compared with Pl, muscle glycogen content was higher ( P < 0.05) in the trained leg in both Cr and Cr+P. Supplements had no effect on GLUT-4 expression or glycogen content in contralateral control legs. Area under the glucose curve during the oral glucose tolerance test was decreased from 232 ± 23 mmol · l−1 · min−1at baseline to 170 ± 23 mmol · l−1 · min−1 at the end of the retraining period in Cr+P ( P < 0.05), but it did not change in Cr or Pl. We conclude that creatine intake stimulates GLUT-4 and glycogen content in human muscle only when combined with changes in habitual activity level. Furthermore, combined protein and creatine supplementation improved oral glucose tolerance, which is supposedly unrelated to the changes in muscle GLUT-4 expression.

AB Purpose: Physiological responses to hypoxia vary between individuals, and genetic factors are conceivably involved. Using a monozygotic twin design, we investigated the role of genetic factors in physiological responses to acute hypoxia. Methods: Thirteen pairs of monozygotic twin brothers participated in two experimental sessions in a normobaric hypoxic facility with a 2-wk interval. In one session, fraction of inspired O2 (FiO2) was gradually reduced to 10.7% (approximately 5300 m altitude) over 5 h. During the next 3 h at 10.7%, FiO2 subjects performed a 20-min submaximal exercise bout (EXSUB, 1.2 W[middle dot]kg-1) and a maximal incremental exercise test (EXMAX). An identical control experiment was done in normoxia. Cardiorespiratory measurements were continuously performed, and 8-h urine output was collected. Results: Compared with normoxia, hypoxia decreased (P < 0.05) arterial O2 saturation (%SpO2) at rest (-22%) and during exercise (-28%). Furthermore, V[spacing dot above]O2max (-39%), HRmax (HR, -8%), maximal pulmonary ventilation (V[spacing dot above]Emax, -11%), and urinary norepinephrine excretion (-31%) were reduced (P < 0.05) whereas HR at rest (25%) and during EXSUB (16%) and V[spacing dot above]E at rest (38%) and during EXSUB (70%) were increased (P < 0.05). However, hypoxia-induced changes ([DELTA]) were not randomly distributed between subjects. Between-pair variance was substantially larger than within-pair variance (P < 0.05) for [DELTA]%SpO2 at rest (approximately threefold) and during exercise (approximately fourfold), [DELTA]V[spacing dot above]O2max (approximately fourfold), [DELTA]HR during exercise (approximately seven- to eightfold), hypoxic ventilatory response (approximately sixfold), and [DELTA] urinary norepinephrine output (approximately threefold). Incidence of acute mountain sickness (AMS) also yielded significant twin similarity (P < 0.05). AMS+ subjects showed approximately 50% greater drop in urinary norepinephrine and lower hypoxic ventilator response than AMS- individuals. Conclusions: Our data suggest that genetic factors regulate cardiorespiratory responses, exercise tolerance, and pathogenesis of AMS symptoms in acute severe hypoxia. Hypoxia-induced sympathetic downregulation was associated with AMS.

Hypoxia-induced muscle wasting is a phenomenon often described at high altitude, which has been attributed to an altered protein metabolism. We hypothesized that acute normobaric hypoxia would favo...

In team pursuit, the drag of a group of cyclists riding in a pace line is dependent on several factors, such as anthropometric characteristics (stature) and position of each cyclist as well as the sequence in which they ride. To increase insight in drag reduction mechanisms, the aerodynamic drag of four cyclists riding in a pace line was investigated, using four different cyclists, and for four different sequences. In addition, each sequence was evaluated for two arm spacings. Instead of conventional field or wind tunnel experiments, a validated numerical approach (computational fluid dynamics) was used to evaluate cyclist drag, where the bicycles were not included in the model. The cyclist drag was clearly dependent on his position in the pace line, where second and subsequent positions experienced a drag reduction up to 40%, compared to an individual cyclist. Individual differences in stature and position on the bicycle led to an intercyclist variation of this drag reduction at a specific position in the sequence, but also to a variation of the total drag of the group for different sequences. A larger drag area for the group was found when riding with wider arm spacing. Such numerical studies on cyclists in a pace line are useful for determining the optimal cyclist sequence for team pursuit. ispartof: Journal of Biomechanical Engineering vol:136 issue:1 pages:011005-011005 ispartof: location:United States status: published

1. We investigated the effect of oral creatine supplementation during leg immobilization and rehabilitation on muscle volume and function, and on myogenic transcription factor expression in human subjects. 2. A double-blind trial was performed in young healthy volunteers (n = 22). A cast was used to immobilize the right leg for 2 weeks. Thereafter the subjects participated in a knee-extension rehabilitation programme (3 sessions x week(-1), 10 weeks). Half of the subjects received creatine monohydrate (CR; from 20 g down to 5 g daily), whilst the others ingested placebo (P; maltodextrin). 3. Before and after immobilization, and after 3 and 10 weeks of rehabilitation training, the cross-sectional area (CSA) of the quadriceps muscle was assessed by NMR imaging. In addition, an isokinetic dynamometer was used to measure maximal knee-extension power (Wmax), and needle biopsy samples taken from the vastus lateralis muscle were examined to asses expression of the myogenic transcription factors MyoD, myogenin, Myf5, and MRF4, and muscle fibre diameters. 4. Immobilization decreased quadriceps muscle CSA (approximately 10 %) and Wmax (approximately 25 %) by the same magnitude in both groups. During rehabilitation, CSA and Wmax recovered at a faster rate in CR than in P (P < 0.05 for both parameters). Immobilization changed myogenic factor protein expression in neither P nor CR. However, after rehabilitation myogenin protein expression was increased in P but not in CR (P < 0.05), whilst MRF4 protein expression was increased in CR but not in P (P < 0.05). In addition, the change in MRF4 expression was correlated with the change in mean muscle fibre diameter (r = 0.73, P < 0.05). 5. It is concluded that oral creatine supplementation stimulates muscle hypertrophy during rehabilitative strength training. This effect may be mediated by a creatine-induced change in MRF4 and myogenin expression.

The purpose of this study was to investigate the effect of oral creatine supplementation on muscle GLUT4 protein content and total creatine and glycogen content during muscle disuse and subsequent training. A double-blind placebo-controlled trial was performed with 22 young healthy volunteers. The right leg of each subject was immobilized using a cast for 2 weeks, after which subjects participated in a 10-week heavy resistance training program involving the knee-extensor muscles (three sessions per week). Half of the subjects received creatine monohydrate supplements (20 g daily during the immobilization period and 15 and 5 g daily during the first 3 and the last 7 weeks of rehabilitation training, respectively), whereas the other 11 subjects ingested placebo (maltodextrine). Muscle GLUT4 protein content and glycogen and total creatine concentrations were assayed in needle biopsy samples from the vastus lateralis muscle before and after immobilization and after 3 and 10 weeks of training. Immobilization decreased GLUT4 in the placebo group (-20%, P < 0.05), but not in the creatine group (+9% NS). Glycogen and total creatine were unchanged in both groups during the immobilization period. In the placebo group, during training, GLUT4 was normalized, and glycogen and total creatine were stable. Conversely, in the creatine group, GLUT4 increased by ∼40% (P < 0.05) during rehabilitation. Muscle glycogen and total creatine levels were higher in the creatine group after 3 weeks of rehabilitation (P < 0.05), but not after 10 weeks of rehabilitation. We concluded that 1) oral creatine supplementation offsets the decline in muscle GLUT4 protein content that occurs during immobilization, and 2) oral creatine supplementation increases GLUT4 protein content during subsequent rehabilitation training in healthy subjects.

The interaction of glycogen concentration, insulin and beta-adrenergic stimulation in the regulation of glycogen breakdown was studied in perfused rat muscles. Rats were pre-conditioned to obtain two groups with either normal (N) or 'supercompensated' (SC) muscle glycogen. The next day their hindlimbs were perfused with a medium containing insulin (0, 40 and 100 microU mL(-1)) and/or isoproterenol (0 and 1.5 nmol L(-1)). Contractions were induced by electrical stimulation of the sciatic nerve. Compared with N, glycogen breakdown in white gastrocnemius during contractions was greater in SC at any hormonal combination (P < 0.05). Conversely, in red gastrocnemius (RG) the higher glycogenolytic rate in SC, compared with N, faded as the insulin concentration was raised from 0 to 100 microU mL(-1). However, isoproterenol restored the higher glycogenolytic rate in SC. In any condition, RG glycogen synthase fractional activity was lower (P < 0.05) during contractions in SC than in N. Furthermore, the percentage of phosphorylase a was higher in SC except when muscles were exposed to insulin alone. In conclusion, high initial glycogen concentration in fast-glycolytic muscle causes high glycogenolytic rate during contractions, irrespective of hormonal stimulation. In contrast, due to down-regulation of phosphorylase activity, such a relationship does not exist in insulin-stimulated fast-oxidative muscle.

The effect of creatine (Cr) supplementation on muscle isometric torque generation and relaxation was investigated in healthy male volunteers. Maximal torque (Tmax), contraction time (CT) from 0.25 to 0.75 of Tmax, and relaxation time (RT) from 0.75 to 0.25 of Tmax were measured during 12 maximal isometric 3-s elbow flexions interspersed by 10-s rest intervals. Between the pretest and the posttest, subjects ingested Cr monohydrate (4 × 5 g/day; n = 8) or placebo ( n = 8) for 5 days. Pretest Tmax, CT, and RT were similar in Cr and placebo groups. Also in the posttest, Tmax and CT were similar between groups. However, posttest RT was decreased consistently by ∼20% ( P < 0.05) in the Cr group from the first to the last of the 12 contractions. In addition, the mean decrease in RT after Cr loading was positively correlated with pretest RT ( r = 0.82). It is concluded that Cr loading facilitates the rate of muscle relaxation during brief isometric muscle contractions without affecting torque production.

1. The effect of A1-adenosine receptor antagonism via 8-cyclopentyl-1,3-dipropyl-xanthine (CPDPX) on the stimulation of skeletal muscle glucose uptake by contractions and hypoxia was investigated in isolated perfused rat hindquarters. The standard perfusate contained either no insulin or a submaximal insulin concentration at 100 microU ml-1. 2. Muscles were stimulated to contract for 45 min by intermittent tetanic stimulation of the sciatic nerve. Hypoxia was induced by reducing perfusate haematocrit from 30% to 10% on the one hand, and by switching the gassing of the perfusate from a 35% to a 0% O2 mixture for 60 min on the other hand. The effect of contractions and hypoxia alone, or in combination, was investigated. 3. Hypoxia-induced muscle glucose uptake was not altered by CPDPX in the absence or presence of insulin. In contrast, contraction-induced glucose uptake was reduced by approximately 25 % (P0.05) by exposure of muscles to CPDPX. CPDPX did not affect hindlimb glucose uptake either before or after contractions. 4. The increment of muscle glucose uptake during hypoxia combined with contractions was greater (P0.05) than the effect of hypoxia alone. 5. The current findings provide evidence that the mechanism by which hypoxia stimulates muscle glucose uptake is, at least in part, different from the mechanism of glucose uptake stimulation by contractions, because (i) A1-adenosine receptors regulate insulin-mediated glucose uptake in muscle during contractions but not during hypoxia and (ii) submaximal hypoxia and contractions are additive stimuli to muscle glucose uptake.

Oral creatine supplementation has been shown to improve power output during high intensity intermittent muscle contractions. Facilitated muscle phosphocreatine (PCr) resynthesis, by virtue of elevated intracellular PCr concentration, might contribute to this ergogenic action. Therefore, the effect of creatine loading (C: 25 g X d(-1) for 5 d) on muscle PCr breakdown and resynthesis and muscle performance during high intensity intermittent muscle contractions was investigated.A double-blind randomized cross-over study was performed in young healthy male volunteers (N = 9). 31P-NMR spectroscopy of the m. gastrocnemius and isokinetic dynamometry of knee-extension torque were performed before and after 2 and 5 d of either placebo (P) or C administration.Compared with P, 2 and 5 d of C increased (P0.05) resting muscle PCr concentration by 11% and 16%, respectively. Furthermore, torque production during maximal intermittent knee extensions, including the first bout of contractions, was increased (P0.05) by 5-13% by either 2 or 5 d of C. However, compared with P, the rate of PCr breakdown and resynthesis during intermittent isometric contractions of the calf was not significantly affected by C.Creatine loading raises muscle PCr concentration and improves performance during rapid and dynamic intermittent muscle contractions. Creatine loading does not facilitate muscle PCr resynthesis during intermittent isometric muscle contractions.

The effect of creatine loading on endurance capacity and sprint performance was investigated in elite cyclists according to a double-blind cross-over study design. Subjects (n = 12) underwent on 3 occasions and separated by 5 week wash-out periods, a 2 h 30 min standardized endurance protocol on their own race bicycle, which was mounted on an electromagnetically braked roller-system, whereupon they cycled to exhaustion at their predetermined 4 mmol lactate threshold. Immediately thereafter they performed 5 maximal 10 second sprints, separated by 2 min recovery intervals, on a Monark bicycle ergometer at 6 kg resistance on the flywheel. Before the exercise test, subjects were either creatine loaded (C: 25 g creatine monohydrate/day, 5 days) or were creatine loaded plus ingested creatine during the exercise test (CC: 5 g/h), or received placebo (P). Compared with P, C but not CC increased (p

In the present studies, the Leuven Tennis Performance Test (LTPT), a newly developed test procedure to measure stroke performance in match-like conditions in elite tennis players, was evaluated as to its value for research purposes. The LTPT is enacted on a regular tennis court. It consists of first and second services, and of returning balls projected by a machine to target zones indicated by a lighted sign. Neutral, defensive, and offensive tactical situations are elicited by appropriately programming the machine. Stroke quality is determined from simultaneous measurements of error rate, ball velocity, and precision of ball placement. A velocity/precision (VP) an a velocity/precision/error (VPE) index are also calculated. The validity and sensitivity of the LTPT were determined by verifying whether LTPT scores reflect minor differences in tennis ranking on the one hand and the effects of fatigue on the other hand. Compared with lower ranked players, higher ones made fewer errors (P < 0.05). In addition, stroke velocity was higher (P < 0.05), and lateral stroke precision, VP, and VPE scores were better (P < 0.05) in the latter. Furthermore, fatigue induced by a prolonged tennis load increased (P < 0.05) error rate and decreased (P < 0.05) stroke velocity and the VP and VPE indices. It is concluded that the LTPT is an accurate, reliable, and valid instrument for the evaluation of stroke quality in high-level tennis players.

Department of Kinesiology, Faculty of Physical Education and Physiotherapy, Katholieke Universiteit Leuven, Belgium.The effect of carbohydrate supplementation on stroke quality during prolonged simulated tennis match-play was investigated. Well-trained tennis palyers reported to the test center three times. At each occasion they performed a pretest, consisting of the leuven Tennis Performance Test (LTPT) and a shuttle run (SHR), which they repeated (posttest) after a 2-h strenuous training session. Throughout the test session, they received in a double blind random order either a placebo drink (P), a carbohydrate solution (0.7 gxkg(-1) BWxh(-1); CHO), or CHO plus a dose of caffeine (5 mg per kg BW). Stroke quality was evaluated during the LTPT by means of measurements of error rate, ball velocity, precision of ball placement, and a velocity-precision (VP) and a velocity-precision-error (VPE) index. Pretest scores were similar during P and CHO. During P, compared with the pretest, stroke quality during the posttest deteriorated (P < 0.05) both for the first service and strokes during defensive rallies and for SHR performance. However, compared with P, the increase in error rate and number of nonreached balls indefensive rallies was smaller (P < 0.05) during CHO. Similarily, CHO attenuated (P < 0.05) the increase in error rate and the decrease in both the VP (P < 0.1) and VPE (P < 0.05) indices for the first service upon fatigue. Furthermore, CHO improved posttest SHR performance. Stroke quality and SHR time were similar during CHO alone and during combined CHO plus caffeine administration, both for the pretest and for the pretest and for the posttest. It is concluded that CHO supplementation improves stroke quality during the final stages of prolonged tennis play. The data prove that CHO intake may facilitate the maintenance of physical quality during long-lasting intermittent exercise to fatigue.Publication Types: Clinical Trial Randomized Controlled Trial

Hypoxia-induced muscle wasting is a phenomenon often described with prolonged stays at high altitude, which has been attributed to altered protein metabolism. We hypothesized that acute normobaric hypoxia would induce a negative net protein balance by repressing anabolic and activating proteolytic signaling pathways at rest and postexercise and that those changes could be partially genetically determined. Eleven monozygotic twins participated in an experimental trial in normoxia and hypoxia (10.7% O2). Muscle biopsy samples were obtained before and after a 20-min moderate cycling exercise. In hypoxia at rest, autophagic flux was increased, as indicated by an increased microtubule-associated protein 1 light chain 3 type II/I (LC3-II/I) ratio (+25%) and LC3-II expression (+60%) and decreased p62/SQSTM1 expression (-25%; P

Eighteen patients with asthma were evaluated during preparation to climb to extreme altitude in order to study the effects of low fractional inspired oxygen (FiO(2)), prolonged exposure to cold air and high altitude on lung function, asthma control and airway inflammation.Spirometry and airway inflammation (fractional exhaled nitric oxide (FeNO) and induced sputum) were studied under different test conditions: hypoxic (FiO(2)=11%) exercise test, 24-hour cold exposure (-5°C) and before, during and after an expedition that involved climbing the Aconcagua mountain (6965 m).Forced expiratory volume in 1 s (FEV(1)) and FeNO values were slightly lower (p0.04) after 1 h of normobaric hypoxia. FEV(1) decreased (p=0.009) after 24-hour cold exposure, accompanied by increased sputum neutrophilia (p0.01). During the expedition FEV(1) and forced vital capacity decreased (maximum FEV(1) decrease of 12.3% at 4300 m) and asthma symptoms slightly increased. After the expedition the Asthma Control Test score and prebronchodilator FEV(1) were reduced (p0.02), sputum neutrophil count was increased (p=0.04) and sputum myeloperoxidase levels, sputum interleukin 17 mRNA, serum and sputum vascular endothelial growth factor A levels were significantly higher compared with baseline. Patients with asthma with the lowest oxygen saturation during the hypoxic exercise test were more prone to develop acute mountain sickness.Exposure to environmental conditions at high altitude (hypoxia, exercise, cold) was associated with a moderate loss of asthma control, increased airway obstruction and neutrophilic airway inflammation. The cold temperature is probably the most important contributing factor as 24-hour cold exposure by itself induced similar effects.

In this study, we compared the effect of sprint interval training (SIT) in normoxia versus hypoxia on muscle glycolytic and oxidative capacity, monocarboxylate transporter content, and endurance exercise performance.Healthy male volunteers (18-30 yr) performed 6 wk of SIT on a cycling ergometer (30-s sprints vs 4.5-min rest intervals; 3 d · wk(-1)) in either normobaric hypoxia (HYP, FiO2 = 14.4%, n = 10) or normoxia (NOR, FiO2 = 20.9%, n = 9). The control group did not train (CON, n = 10). Training load was increased from four sprints per session in week 1 to nine sprints in week 6. Before and after SIT, subjects performed a maximal incremental exercise test plus a 10-min simulated time trial on a cycle ergometer in both normoxia (MAX nor and TT nor) and hypoxia (MAX hyp and TT hyp). A needle biopsy was taken from musculus vastus lateralis at rest 5-6 d after the last exercise session.SIT increased muscle phosphofructokinase activity more in HYP (+59%, P0.05) than that in NOR (+17%), whereas citrate synthase activity was similar between groups. Compared with the pretest, power outputs corresponding to 4 mmol blood lactate in HYP during MAX nor (+7%) and MAX hyp (+9%) were slightly increased (P0.05), whereas values were constant in NOR. V·O 2max in MAX nor and TT performance in TT nor and TT hyp were increased by ≈ 6%-8% (P0.05) in either group. The training elevated monocarboxylate transporter 1 protein content by ≈ 70% (P0.05). In CON, all measurements were constant throughout the study.SIT in hypoxia up-regulated muscle phosphofructokinase activity and the anaerobic threshold more than SIT in normoxia but did not enhance endurance exercise performance.

Glucose uptake rate in active skeletal muscles is markedly increased during exercise. This increase reflects a multifactorial process involving both local and systemic mechanisms that cooperate to stimulate glucose extraction and glucose delivery to the muscle cells. Increased glucose extraction is effected primarily via mechanisms exerted within the muscle cell related to the contractile activity per se. Yet contractions become a more potent stimulus of muscle glucose uptake as the plasma insulin level is increased. In addition, enhanced glucose delivery to muscle, which during exercise is essentially effected via increased blood flow, significantly contributes to stimulate glucose uptake. Again, however, increased glucose delivery appears to be a more potent stimulus of muscle glucose uptake as the circulating insulin level is increased. Furthermore, contractions and elevated flow prove to be additive stimuli of muscle glucose uptake at any plasma insulin level. In conclusion, the extent to which muscle glucose uptake is stimulated during exercise depends on various factors, including 1) the intensity of the contractile activity, 2) the magnitude of the exercise-associated increase in muscle blood flow, and 3) the circulating insulin level.

The extent to which muscle glycogen depletion affects plasma free fatty acid (FFA) metabolism in contracting skeletal muscle is not well characterized. To study this question, rats were glycogen depleted (GD) or supercompensated (SC) by swimming exercise and diet treatment 24 h before perfusion of their isolated hindquarters at rest and during electrically induced muscle contractions. After 20 min of equilibration with glucose (6 mM), palmitate (2,000 microM), and [1–14C]palmitate, palmitate uptake and oxidation were found to be similar between groups at rest and during electrical stimulation. Palmitate uptake increased by 55% during electrical stimulation and averaged 2.75 +/- 0.56 mumol.g-1.h-1. Resting palmitate oxidation averaged 0.14 +/- 0.03 mumol.g-1.h-1 and increased to 0.53 +/- 0.06 and 0.47 +/- 0.08 mumol.g-1.h-1 during electrical stimulation in GD and SC, respectively. Glucose uptake was significantly higher in GD than in SC at rest and during electrical stimulation and significantly increased in both groups during electrical stimulation to reach values of 11.8 +/- 1.2 and 7.6 +/- 1.4 mumol.g-1.h-1, respectively. Lactate release was lower in GD than in SC at rest and during electrical stimulation and was highest after 2 min of stimulation in both groups. Additional experiments at perfusate palmitate concentrations of 600–900 microM yielded similar results. These results show that, in contracting perfused skeletal muscle, muscle glycogen depletion increases glucose utilization but does not affect total plasma FFA oxidation, suggesting that regulation within pathways of carbohydrate metabolism takes precedence over regulation between pathways of lipid and carbohydrate metabolism.

The relative role of contractions, insulin, and increased supply of glucose and insulin, via an increase in blood flow, in stimulating glucose uptake in skeletal muscle during contractions was studied in isolated perfused rat hindlimbs. ffindlimbs were perfused with a standard per-fusate medium containing 6 mmol/1 glucose and four different insulin concentrations (0, 100, 500, and 20,000 μU/ml). Contractions were induced by supramaximal intermittent electrical stimulation of the sciatic nerve. Three different perfusion protocols were used: 1) muscles were stimulated to contract without concomitantly increasing perfusate flow; 2) flow was increased in the absence of electrical stimulation; and 3) muscles were stimulated to contract together with a flow increase. Both contractions and increased flow of perfusate, applied as separate stimuli, increased (P < 0.05) glucose uptake in the absence of insulin. Yet when submaximal insulin concentrations were added to the perfusate, the stimulatory action of both contractions and increased blood flow on muscle glucose uptake was augmented. The higher the submaximal insulin concentration, the greater the increment (P < 0.05). This effect, however, faded at supra-maximal insulin concentration. Electrical stimulation associated with an increase in perfusion flow rate produced a greater (P < 0.05) rise in glucose uptake than did contractions alone. In fact, stimulation of muscle glucose uptake by contractions and increased flow proved to be additive at any insulin concentration. We conclude that contractions and increased blood flow act as additional stimuli to muscle glucose uptake at any insulin concentration. Furthermore, insulin appears to be a major contributor to stimulating glucose uptake rate in muscle during contractions by facilitating both the flow-induced and the contraction-induced increment in muscle glucose uptake.

Background High-intensity exercise typically leads to a depletion of body carbohydrate stores, primarily muscle glycogen. Therefore, typical ‘sports recovery drinks’ include a high carbohydrate dose, which stimulate muscle glucose uptake and glycogen re-synthesis via increased plasma insulin level. Thus, interventions that elevate plasma insulin following exercise could facilitate repletion of muscle glycogen stores, and serve as a useful ‘recovery agent’. There are some indications that extracts of the prickly pear cactus (Opuntiaficus-indica; OFI) can stimulate insulin secretion.

A simple method for the determination of nitrite and nitrate in human plasma has been developed using CZE with minimal sample preparation. Field-amplified sample stacking (FASS) was used to achieve submicromolar detection by dilution of the plasma sample with deionized water. In CZE, the separation of nitrite and nitrate was achieved within 10 min without adding EOF modifier. The optimal condition was achieved with 50 mM phosphate buffer at pH 9.3. The ninefold diluted plasma samples were injected hydrodynamically for 40 s into a 60 cm×75 μm id uncoated fused-silica capillary. The separation voltage was 20 kV (negative potential) and UV detection was performed at 214 nm. The linearity curves for nitrite and nitrate were obtained by the standard addition method. The estimated LODs for nitrite and nitrate in ninefold diluted plasma sample were 0.05 and 0.07 μM, respectively. The LODs for nitrite and nitrate in original plasma samples were 0.45 and 0.63 μM. The intra- and inter-day precisions for both analytes were

This study aims at investigating drag and convective heat transfer for cyclists at a high spatial resolution. Such an increased spatial resolution, when combined with flow-field data, can increase insight in drag reduction mechanisms and in the thermo-physiological response of cyclists related to heat stress and hygrothermal performance of clothing. Computational fluid dynamics (steady Reynolds-averaged Navier-Stokes) is used to evaluate the drag and convective heat transfer of 19 body segments of a cyclist for three different cyclist positions. The influence of wind speed on the drag is analysed, indicating a pronounced Reynolds number dependency on the drag, where more streamlined positions show a dependency up to higher Reynolds numbers. The drag and convective heat transfer coefficient (CHTC) of the body segments and the entire cyclist are compared for all positions at racing speeds, showing high drag values for the head, legs and arms and high CHTCs for the legs, arms, hands and feet. The drag areas of individual body segments differ markedly for different cyclist positions whereas the convective heat losses of the body segments are found to be less sensitive to the position. CHTC-wind speed correlations are derived, in which the power-law exponent does not differ significantly for the individual body segments for all positions, where an average value of 0.84 is found. Similar CFD studies can be performed to assess drag and CHTCs at a higher spatial resolution for applications in other sport disciplines, bicycle equipment design or to assess convective moisture transfer. ispartof: Journal of Biomechanics vol:44 issue:9 pages:1695-1701 ispartof: location:United States status: published

Brandt N, De Bock K, Richter EA, Hespel P. Cafeteria diet-induced insulin resistance is not associated with decreased insulin signaling or AMPK activity and is alleviated by physical training in rats. Am J Physiol Endocrinol Metab 299: E215-E224, 2010. First published May 18, 2010; doi:10.1152/ajpendo.00098.2010.-Excess energy intake via a palatable low-fat diet (cafeteria diet) is known to induce obesity and glucose intolerance in rats. However, the molecular mechanisms behind this adaptation are not known, and it is also not known whether exercise training can reverse it. Male Wistar rats were assigned to 12-wk intervention groups: chow-fed controls (CON), cafeteria diet (CAF), and cafeteria diet plus swimming exercise during the last 4 wk (CAF(TR)). CAF feeding led to increased body weight (16%, P < 0.01) and increased plasma glucose (P < 0.05) and insulin levels (P < 0.01) during an IVGTT, which was counteracted by training. In the perfused hindlimb, insulin-stimulated glucose transport in red gastrocnemius muscle was completely abolished in CAF and rescued by exercise training. Apart from a tendency toward an similar to 20% reduction in both basal and insulin-stimulated Akt Ser(473) phosphorylation (P = 0.051) in the CAF group, there were no differences in insulin signaling (IR Tyr(1150/1151), PI 3-kinase activity, Akt Thr(308), TBC1D4 Thr(642), GSK3-alpha/beta Ser(21/9)) or changes in AMPK alpha 1 or -alpha 2, GLUT4, Munc18c, or syntaxin 4 protein expression or in phosphorylation of AMPK Thr(172) among the groups. In conclusion, surplus energy intake of a palatable but low-fat cafeteria diet resulted in obesity and insulin resistance that was rescued by exercise training. Interestingly, insulin resistance was not accompanied by major defects in the insulin-signaling cascade or in altered AMPK expression or phosphorylation. Thus, compared with previous studies of high-fat feeding, where insulin signaling is significantly impaired, the mechanism by which CAF diet induces insulin resistance seems different. ispartof: American Journal of Physiology: Endocrinology and Metabolism vol:299 issue:2 pages:E215-E224 ispartof: location:United States status: published

Intramyocellular lipids (IMCL) and mitochondrial uncoupling protein-3 (UCP3) have been implicated in the development of muscular insulin resistance. This study aimed to investigate the role of IMCL and UCP3 in the development of glucose intolerance and muscular insulin resistance during 12 weeks of an obesity-inducing 'cafeteria-style' diet alone (CAF), or in conjunction with exercise training from weeks 8-12 (CAFTR), in rats. At the end of the intervention period, gain in body weight was 20% higher in CAF (305+/-10 g) than controls (CON) (255+/-14 g; p

The present study aimed at comparing the responses of myogenic regulatory factors and signaling pathways involved in muscle protein synthesis after a resistance training session performed in either the fasted or fed state. According to a randomized crossover study design, six young male subjects participated in two experimental sessions separated by 3 weeks. In each session, they performed a standardized resistance training. After the sessions, they received during a 4-h recovery period 6 ml/kg b.w. h of a solution containing carbohydrates (50 g/l), protein hydrolysate (33 g/l), and leucine (16.6 g/l). On one occasion, the resistance exercise session was performed after the intake of a carbohydrate-rich breakfast (B), whereas in the other session they remained fasted (F). Needle biopsies from m. vastus lateralis were obtained before (Rest), and 1 h (+1h) and 4 h (+4h) after exercise. Myogenin, MRF4, and MyoD1 mRNA contents were determined by RT-PCR. Phosphorylation of PKB (protein kinase B), GSK3, p70(s6k) (p70 ribosomal S6 kinase), eIF2B, eEF2 (eukaryotic elongation factor 2), ERK1/2, and p38 was measured via western blotting. Compared with F, the pre-exercise phosphorylation states of PKB and p70(s6k) were higher in B, whereas those of eIF2B and eEF2 were lower. During recovery, the phosphorylation state of p70(s6k) was lower in B than in F (p = 0.02). There were no differences in basal mRNA contents between B and F. However, compared with F at +1h, MyoD1 and MRF4 mRNA contents were lower in B (p < 0.05). Our results indicate that prior fasting may stimulate the intramyocellular anabolic response to ingestion of a carbohydrate/protein/leucine mixture following a heavy resistance training session.

In this study, some important metabolic responses to exercise will be discussed, and aspects of particular interest for patients with diabetes mellitus will be emphasized. Alterations in the metabolic responses to exercise induced by physical endurance training and consequences of training for metabolism of plasma lipids and lipoproteins will be discussed. Glucoregulation during exercise is not perfect in normal subjects and is less so in patients with diabetes mellitus. For instance, during intense exercise, large increases in the plasma glucose concentration occur and a state of insulin resistance exists for a few hours after intense exercise. Even so, increased sensitivity to insulin is found the day after intense exercise and also shortly after more moderate intensity exercise, both in healthy subjects and in patients with diabetes mellitus. Increased sensitivity to insulin is also found after endurance training, whereas insulin sensitivity is decreased after inactivity. Exercise training increases the ability of muscle to take up and oxidize free fatty acids during exercise and also increases the activity of the enzyme lipoprotein lipase in muscle. The activity of lipoprotein lipase in muscle correlates with muscle insulin sensitivity. This might explain why insulin resistance is often associated with hypercholesterolemia, hypertriglyceridemia, and low high-density lipoprotein cholesterol.

The influence of differences in glycogen concentration on glycogen breakdown and on phosphorylase activity was investigated in perfused contracting rat skeletal muscle. The rats were preconditioned by a combination of swimming exercise and diet (carbohydrate-free or carbohydrate-rich) in order to obtain four sub-groups of rats with varying resting muscle glycogen concentrations (range 10-60 mumol/g wet wt.). Pre-contraction muscle glycogen concentration was closely positively correlated with glycogen breakdown over 15 min of intermittent short tetanic contractions (r = 0.75; P less than 0.001; n = 56) at the same tension development and oxygen uptake. Additional studies in supercompensated and glycogen-depleted hindquarters during electrical stimulation for 20 s or 2 min revealed that the difference in glycogenolytic rate was found at the beginning rather than at the end of the contraction period. Phosphorylase alpha activity was approximately twice as high (P less than 0.001) in supercompensated muscles as in glycogen-depleted muscles after 20 s as well as after 2 min of contractions. It is concluded that glycogen concentration is an important determinant of phosphorylase activity in contracting skeletal muscle, and probably via this mechanism a regulator of glycogenolytic rate during muscle contraction.

Three different cyclist positions were evaluated with Computational Fluid Dynamics (CFD) and wind-tunnel experiments were used to provide reliable data to evaluate the accuracy of the CFD simulations. Specific features of this study are: (1) both steady Reynolds-averaged Navier-Stokes (RANS) and unsteady flow modelling, with more advanced turbulence modelling techniques (Large-Eddy Simulation - LES), were evaluated; (2) the boundary layer on the cyclist's surface was resolved entirely with low-Reynolds number modelling, instead of modelling it with wall functions; (3) apart from drag measurements, also surface pressure measurements on the cyclist's body were performed in the wind-tunnel experiment, which provided the basis for a more detailed evaluation of the predicted flow field by CFD. The results show that the simulated and measured drag areas differed about 11% (RANS) and 7% (LES), which is considered to be a close agreement in CFD studies. A fair agreement with wind-tunnel data was obtained for the predicted surface pressures, especially with LES. Despite the higher accuracy of LES, its much higher computational cost could make RANS more attractive for practical use in some situations. CFD is found to be a valuable tool to evaluate the drag of different cyclist positions and to investigate the influence of small adjustments in the cyclist's position. A strong advantage of CFD is that detailed flow field information is obtained, which cannot easily be obtained from wind-tunnel tests. This detailed information allows more insight in the causes of the drag force and provides better guidance for position improvements. ispartof: Journal of Biomechanics vol:43 issue:7 pages:1262-1268 ispartof: location:United States status: published

Muscle frailty is considered a major cause of disability in the elderly and chronically ill. However, the exact role of androgen receptor (AR) signaling in muscle remains unclear. Therefore, a postmitotic myocyte-specific AR knockout (mARKO) mouse model was created and investigated together with a mouse model with ubiquitous AR deletion. Muscles from mARKO mice displayed a marked reduction in AR protein (60–88%). Interestingly, body weights and lean body mass were lower in mARKO vs. control mice (−8%). The weight of the highly androgen-sensitive musculus levator ani was significantly reduced (−46%), whereas the weights of other peripheral skeletal muscles were not or only slightly reduced. mARKO mice had lower intra-abdominal fat but did not demonstrate a cortical or trabecular bone phenotype, indicating that selective ablation of the AR in myocytes affected male body composition but not skeletal homeostasis. Furthermore, muscle contractile performance in mARKO mice did not differ from their controls. Myocyte-specific AR ablation resulted in a conversion of fast toward slow fibers, without affecting muscle strength or fatigue. Similar results were obtained in ubiquitous AR deletion, showing lower body weight, whereas some but not all muscle weights were reduced. The percent slow fibers was increased, but no changes in muscle strength or fatigue could be detected. Together, our findings show that myocyte AR signaling contributes to the maintenance of muscle mass and fiber type regulation but not to muscle strength or fatigue. The levator ani weight remains the most sensitive and specific marker of AR-mediated anabolic action on muscle.

The daily oral ingestion of supplementary creatine monohydrate can substantially elevate the creatine content of human skeletal muscle. This chapter aims to summarize the current knowledge regarding the impact muscle creatine loading can have on exercise performance and rehabilitation. The major part of the elevation of muscle creatine content is already obtained after one week of supplementation, and the response can be further enhanced by a concomitant exercise or insulin stimulus. The elevated muscle creatine content moderately improves contractile performance in sports with repeated high-intensity exercise bouts. More chronic ergogenic effects of creatine are to be expected when combined with several weeks of training. A more pronounced muscle hypertrophy and a faster recovery from atrophy have been demonstrated in humans involved in resistance training. The mechanism behind this anabolic effect of creatine may relate to satellite cell proliferation, myogenic transcription factors and insulin-like growth factor-1 signalling. An additional effect of creatine supplementation, mostly when combined with training, is enhanced muscle glycogen accumulation and glucose transporter (GLUT4) expression. Thus, creatine may also be beneficial in sport competition and training characterized by daily glycogen depletion, as well as provide therapeutic value in the insulin-resistant state.

The histidine-containing dipeptides (HCD) carnosine and anserine are found in high concentrations in mammalian skeletal muscle. Given its versatile biologic properties, such as antioxidative, antiglycation, and pH buffering capacity, carnosine has been implicated as a protective factor in the aging process. The present study aimed to systematically explore age-related changes in skeletal muscles HCD content in a murine model of accelerated aging. Additionally, we investigated the effect of lifelong creatine supplementation on muscle HCD content and contractile fatiguability. Male senescence-accelerated mice (SAMP8) were fed control or creatine-supplemented (2% of food intake) diet from the age of 10 to 60 weeks. At week 10, 25, and 60, tibialis anterior muscles were dissected and analysed for HCD and taurine content by HPLC. Soleus and EDL muscles were tested for in vitro contractile fatigue and recovery. From 10 to 60 weeks of age, muscular carnosine (-45%), taurine (-24%), and total creatine (-42%) concentrations gradually and significantly decreased. At 25 but not at 60 weeks, oral creatine supplementation significantly increased carnosine (+88%) and anserine (+40%) content compared to age-matched control-fed animals. Taurine and total creatine content were not affected by creatine supplementation at any age. Creatine-treated mice showed attenuated muscle fatigue (soleus) and enhanced force recovery (m. extensor digitorum longus [EDL]) compared to controls at 25 weeks, but not at 60 weeks. From the present study, we can conclude that skeletal muscle tissue exhibits a significant decline in HCD content at old age. Oral creatine supplementation is able to transiently but potently increase muscle carnosine and anserine content, which coincides with improved resistance to contractile fatigue.

Age-related skeletal muscle sarcopenia is linked with increases in falls, fractures, and death and therefore has important socioeconomic consequences. The molecular mechanisms controlling age-related muscle loss in humans are not well understood, but are likely to involve multiple signaling pathways. This study investigated the regulation of several genes and proteins involved in the activation of key signaling pathways promoting muscle hypertrophy, including GH/STAT5, IGF-1/Akt/GSK-3beta/4E-BP1, and muscle atrophy, including TNFalpha/SOCS-3 and Akt/FKHR/atrogene, in muscle biopsies from 13 young (20 +/- 0.2 years) and 16 older (70 +/- 0.3 years) males. In the older males compared to the young subjects, muscle fiber cross-sectional area was reduced by 40-45% in the type II muscle fibers. TNFalpha and SOCS-3 were increased by 2.8 and 1.5 fold, respectively. Growth hormone receptor protein (GHR) and IGF-1 mRNA were decreased by 45%. Total Akt, but not phosphorylated Akt, was increased by 2.5 fold, which corresponded to a 30% reduction in the efficiency of Akt phosphorylation in the older subjects. Phosphorylated and total GSK-3beta were increased by 1.5 and 1.8 fold, respectively, while 4E-BP1 levels were not changed. Nuclear FKHR and FKHRL1 were decreased by 73 and 50%, respectively, with no changes in their atrophy target genes, atrogin-1 and MuRF1. Myostatin mRNA and protein levels were significantly elevated by 2 and 1.4 fold. Human sarcopenia may be linked to a reduction in the activity or sensitivity of anabolic signaling proteins such as GHR, IGF-1, and Akt. TNFalpha, SOCS-3, and myostatin are potential candidates influencing this anabolic perturbation. ispartof: Rejuvenation research vol:11 issue:1 pages:163-175 ispartof: location:United States status: published

HIF prolyl hydroxylases (PHD1-3) are oxygen sensors that regulate the stability of the hypoxia-inducible factors (HIFs) in an oxygen-dependent manner. Here, we show that loss of Phd1 lowers oxygen consumption in skeletal muscle by reprogramming glucose metabolism from oxidative to more anaerobic ATP production through activation of a Pparalpha pathway. This metabolic adaptation to oxygen conservation impairs oxidative muscle performance in healthy conditions, but it provides acute protection of myofibers against lethal ischemia. Hypoxia tolerance is not due to HIF-dependent angiogenesis, erythropoiesis or vasodilation, but rather to reduced generation of oxidative stress, which allows Phd1-deficient myofibers to preserve mitochondrial respiration. Hypoxia tolerance relies primarily on Hif-2alpha and was not observed in heterozygous Phd2-deficient or homozygous Phd3-deficient mice. Of medical importance, conditional knockdown of Phd1 also rapidly induces hypoxia tolerance. These findings delineate a new role of Phd1 in hypoxia tolerance and offer new treatment perspectives for disorders characterized by oxidative stress. ispartof: Nature Genetics vol:40 issue:2 pages:170-180 ispartof: location:United States status: published

Skeletal muscle gene response to exercise depends on nutritional status during and after exercise, but it is unknown whether muscle adaptations to endurance training are affected by nutritional status during training sessions. Therefore, this study investigated the effect of an endurance training program (6 wk, 3 day/wk, 1-2 h, 75% of peak (V) over dot O-2) in moderately active males. They trained in the fasted (F; n = 10) or carbohydratefed state (CHO; n = 10) while receiving a standardized diet [65 percent of total energy intake (En) from carbohydrates, 20% En fat, 15% En protein]. Before and after the training period, substrate use during a 2-h exercise bout was determined. During these experimental sessions, all subjects were in a fed condition and received extra carbohydrates (1 g.kg body wt(-1) . h(-1)). Peak (V) over dot O-2 (+7%), succinate dehydrogenase activity, GLUT4, and hexokinase II content were similarly increased between F and CHO. Fatty acid binding protein (FABPm) content increased significantly in F (P = 0.007). Intramyocellular triglyceride content (IMCL) remained unchanged in both groups. After training, pre-exercise glycogen content was higher in CHO (545 +/- 19 mmol/ kg dry wt; P = 0.02), but not in F (434 +/- 32 mmol/ kg dry wt; P = 0.23). For a given initial glycogen content, F blunted exercise-induced glycogen breakdown when compared with CHO (P = 0.04). Neither IMCL breakdown (P = 0.23) nor fat oxidation rates during exercise were altered by training. Thus short-term training elicits similar adaptations in peak (V) over dot O-2 whether carried out in the fasted or carbohydrate-fed state. Although there was a decrease in exercise-induced glycogen breakdown and an increase in proteins involved in fat handling after fasting training, fat oxidation during exercise with carbohydrate intake was not changed. ispartof: Journal of applied physiology vol:104 issue:4 pages:1045-1055 ispartof: location:United States status: published

The daily oral ingestion of supplementary creatine monohydrate can substantially elevate the creatine content of human skeletal muscle. This chapter aims to summarize the current knowledge regarding the impact muscle creatine loading can have on exercise performance and rehabilitation. The major part of the elevation of muscle creatine content is already obtained after one week of supplementation, and the response can be further enhanced by a concomitant exercise or insulin stimulus. The elevated muscle creatine content moderately improves contractile performance in sports with repeated high-intensity exercise bouts. More chronic ergogenic effects of creatine are to be expected when combined with several weeks of training. A more pronounced muscle hypertrophy and a faster recovery from atrophy have been demonstrated in humans involved in resistance training. The mechanism behind this anabolic effect of creatine may relate to satellite cell proliferation, myogenic transcription factors and insulin-like growth factor-1 signalling. An additional effect of creatine supplementation, mostly when combined with training, is enhanced muscle glycogen accumulation and glucose transporter (GLUT4) expression. Thus, creatine may also be beneficial in sport competition and training characterized by daily glycogen depletion, as well as provide therapeutic value in the insulin-resistant state

alpha-Actinin-3 is a Z-disc structural protein found only in type II muscle fibers. The X allele of the R577X polymorphism in the ACTN3 gene results in a premature stop codon and alpha-actinin-3 deficiency in XX homozygotes. Associations between the R577X polymorphism and the muscle-power performance of elite athletes have been described earlier. About 45% of the fiber type proportions are determined by genetic factors. The ACTN3 variant could be one of the contributing genes in the heritability of fiber type distribution through its interaction with calcineurin. The aim of this study was to quantify the association between the polymorphism and muscle fiber type distribution and fast-velocity knee extension strength. Ninety healthy young men (18-29 y) were genotyped for ACTN3 R577X. Knee extensor strength was measured isometrically (45 degrees ) and at different dynamic velocities (100-300 degrees /s) on a programmable dynamometer. Twenty-two XX and twenty-two RR subjects underwent a biopsy of the right vastus lateralis muscle. Fiber type composition was determined by immunohistochemistry. Homozygotes for the R allele show significantly higher relative dynamic quadriceps torques at 300 degrees /s, compared with XX carriers (P0.05). Fiber type characteristics differed significantly between the two genotype groups. The percentage surface and number of type IIx fibers were greater in the RR than the XX genotype group (P0.05), and alpha-actinin-3 protein content is systematically higher in type IIx compared with type IIa fibers (staining intensity ratio IIx to IIa = 1.17). This study shows that the mechanism, by which the ACTN3 polymorphism has its effect on muscle power, might rely on a control function of fiber type proportions.