Buffer capacity and lactate accumulation in skeletal muscle of trained and untrained men

Buffer capacity (β) of skeletal muscle has been determined in trained (n=7) and in sedentary subjects (n=8). The trained subjects were active in ball games where a high degree of anaerobic energy utilization is required. Percentage fibre type occurrence in the thigh muscle was not significantly different in the two groups. However, there was a tendency towards a higher proportion of type I (slow-twitch) fibres (61.5±11.6% vs. 50.2±12.5%) and a lower proportion of type IIB fibres (2.1±3.5% vs 14.1±16.3%) in the trained subjects. The proportion of the cross-sectional area of the muscle biopsies that was made up of type I or type II fibres was not different in the two groups. All subjects performed an isometric contraction of the knee extensors to fatigue at 61% of their maximal voluntary contraction force. Muscle biopsies were taken from the quadriceps femoris muscle at rest and immediately after contraction. The buffer capacity of muscle was calculated from: β= (Muscle lactate (work)-Muscle lactate (rest))/(Muscle pH (rest) -Muscle pH (work)). A higher buffer capacity (p<0.05) was observed in the trained subjects (β=194±30 mmolxpH^-1xkg^-1 dry wt.) compared to the sedentary group (β=164±20) (mean±SD). An unexpected finding was that muscle lactate after contraction to fatigue was lower (30%, p<0.01) and muscle pH was higher (6.80±0.06 vs. 6.61±0.12, p<0.01) in the trained subjects than in the sedentary controls. Creatine phosphate stores were almost completely depleted in both groups. Post-exercise lactate values were related to the proportion of type II fibres in the muscle (p<0.01). There was, however, no statistical correlation betwe β and fibre type occurrence (p>0.05). In summary, the present results indicate that skeletal muscle buffer capacity can be changed by training in man. Furthermore, it is concluded that the lower lactate accumulation and pH decline after an isometric contraction to fatigue that was observed in the trained compared to the sedentary subjects is related to the training per se. However, the tendency towards a lower type I (slowtwitch) fibre percentage in the trained subjects is likely to have contributed to the observed differences.     

Exogenous endothelin-1 causes peripheral insulin resistance in healthy humans

In states of insulin resistance, increased plasma levels of endothelin-1 and a disturbed vascular reactivity have been reported. In order to investigate the effects of endothelin-1 on peripheral insulin sensitivity and the vasoactive interactions between insulin and endothelin-1, six healthy subjects were studied on two different occasions with the euglycaemic hyperinsulinaemic clamp technique combined with an intravenous infusion of either endothelin-1 (4 pmol kg^?1 min^?1) or 0.9% sodium chloride. During the endothelin-1 infusion, arterial plasma endothelin-1 levels rose 10-fold. The endothelin-1 infusion reduced insulin sensitivity as demonstrated by a 31 ± 7% decrease in whole-body glucose uptake (P < 0.05) and a 26 ± 11% fall in leg glucose uptake (P < 0.05) compared with the control protocol. During the state of hyperinsulinaemia, exogenous endothelin-1 increased mean arterial blood pressure by 8 ± 1% (P < 0.05) and decreased splanchnic and renal blood flow by 30 ± 6% (P < 0.001) and 20 ± 4% (P < 0.001), respectively. However, the endothelin-1 infusion did not lower skeletal muscle blood flow measured as leg and forearm blood flow. In summary, exogenous endothelin-1 induced insulin resistance in healthy humans by reducing insulin-dependent glucose uptake in skeletal muscle without decreasing skeletal muscle blood flow. Furthermore, endothelin-1 also preserved its vasoactive potency in the presence of hyperinsulinaemia.     

Interaction of exercise and diet on GLUT‐4 protein and gene expression in Type I and Type II rat skeletal muscle

We determined the interaction of exercise and diet on glucose transporter (GLUT‐4) protein and mRNA expression in type I (soleus) and type II [extensor digitorum longus (EDL)] skeletal muscle. Forty‐eight Sprague Dawley rats were randomly assigned to one of two dietary conditions: high‐fat (FAT, n=24) or high‐carbohydrate (CHO, n=24). Animals in each dietary condition were allocated to one of two groups: control (NT, n=8) or a group that performed 8 weeks of treadmill running (4 sessions week^–1 of 1000 m @ 28 m min^–1, RUN, n=16). Eight trained rats were killed after their final exercise bout for determination of GLUT‐4 protein and mRNA expression: the remainder were killed 48 h after their last session for measurement of muscle glycogen and triacylglycerol concentration. GLUT‐4 protein expression in NT rats was similar in both muscles after 8 weeks of either diet. However, there was a main effect of training such that GLUT‐4 protein was increased in the soleus of rats fed with either diet (P < 0.05) and in the EDL in animals fed with CHO (P < 0.05). There was a significant diet–training interaction on GLUT‐4 mRNA, such that expression was increased in both the soleus (100% ↑P < 0.05) and EDL (142% ↑P < 0.01) in CHO‐fed animals. Trained rats fed with FAT decreased mRNA expression in the EDL (↓ 45%, P < 0.05) but not the soleus (↓ 14%, NS). We conclude that exercise training in CHO‐fed rats increased both GLUT‐4 protein and mRNA expression in type I and type II skeletal muscle. Despite lower GLUT‐4 mRNA in muscles from fat‐fed animals, exercise‐induced increases in GLUT‐4 protein were largely preserved, suggesting that control of GLUT‐4 protein and gene expression are modified independently by exercise and diet.     

Glucose kinetics during exercise in trained men

Six trained men were studied to examine the relative increases in hepatic glucose output and peripheral glucose uptake during 40 min of exercise at 75%Vo_2max. Rates of appearance (Ra) and disappearance (Rd) were measured using a primed, continuous intravenous infusion of D-[3-³H]glucose. Plasma glucose increased (P < 0.05) from 4.8 ± 0.2 mmol I^-1 at rest to 6.2 ± 0.5 mmol l^-1 after 40 min of exercise. Both Ra and Rd increased (P < 0.05) during exercise, however, during the early phase of exercise, Ra exceeded Rd (P < 0.05). Ra peaked at 42.0 ±3.2/tmol kgf¹ min^-1 after approximately 15 min of exercise. In contrast, the highest Rd of 33.9 ± 4.3 μmol kg^-1 min^-1 was measured at the end of exercise. In additional experiments, five men were studied during 40 min of exercise at 70–75%Vo_2max, 2 h after ingestion of the non-selective β-adrenergic antagonist timolol or a placebo capsule. Subjects were unable to complete the exercise bout following timolol, fatiguing after 28.0 ± 4.0 min (P < 0.05). The increase in blood glucose from 4.3 ±0.1 to 4.7 ± 0.3 mmol l^-1 (P < 0.05) following 20 min of exercise under control conditions was completely abolished by prior timolol ingestion (4.2 ± 0.2 to 4.1±0.2 mmol l^-1). These results demonstrate that during exercise at 75%Vo_2max in trained men, hepatic glucose output is not always closely matched to peripheral muscle glucose uptake and may be subject to feed-forward regulation. The abolition of the hyperglycaemia with non-selective β-adrenergic blockade implicates adrenaline in this response.     

Effects of endurance training on oxidative capacity and structural composition of human arm and leg muscles

Six healthy subjects performed endurance training of the same duration with legs and arms consecutively. Performance and muscle structure were measured before and after training in lower and upper limbs. Training induced similar increases in maximal oxygen consumption (6 ± 1 vs. 7 ± 2 mL min^?1 kg^?1: legs vs. arms, P > 0.05) and mitochondrial volume in leg and arm muscles (42 ± 12 vs. 31 ± 11%: legs vs. arms, P > 0.05). The gain in mitochondrial volume after training was achieved solely by increasing the fraction of mitochondria (+40 ± 11%, P < 0.05) in the same muscle volume (+2 ± 2%, P > 0.05) in the legs. In contrast, increased muscle volume (+14 ± 3%, P < 0.05), in addition to a tendency for an increase in mitochondrial fraction (+16 ± 11%, P > 0.05), occurred in the arms after training. Thus, similar improvements in muscle oxidative capacity in upper and lower limbs were brought about by different mechanisms. It is suggested that due to infrequent use and a lack of load-bearing function, arm muscle volume is underdeveloped in untrained, sedentary or detrained/injured subjects and that the mode of endurance training used in this study is sufficient to enlarge arm muscle volume as well as aerobic capacity.     

Brain cooling in diving seals

A previous study reported elevations of insulin-mediated muscle protein synthesis following four days of resistance exercise in rats (Fluckey et al. 1996. Am J Physiol 270, E313–E319). The purpose of this study was to determine if insulin-stimulated muscle glucose uptake (a–v diff.) and 2-deoxyglucose (2-DG) transport were altered under similar conditions. The protocol consisted of squat-like exercises during four sessions with progressively increased weight (70–190 g). Each session consisted of 50 repetitions and sessions were separated by 48 h. Sixteen hours after the last exercise session, basal glucose uptake in perfused hindlimbs was not different (P > 0.05) between exercised (n=6) and non-exercised controls (n=6). However, there was a significant (P < 0.05) attenuation of insulin-stimulated (20 000 μU mL^–1) glucose uptake in exercised vs. non-exercised rats (491 ± 31 vs. 664 ± 58 μmol glucose^–1 g^–1 [15-min insulin period]^–1, respectively). Following resistance exercise, insulin-stimulated 2-DG transport, measured during the last 10 min of the perfusion period, was significantly reduced (P < 0.05) in the soleus, white gastrocnemius and extensor digitorum longus muscles. Additionally, GLUT-4 glucose transporter protein content was significantly reduced (P < 0.05) in white gastrocnemius and extensor digitorum longus muscles. These results demonstrate that insulin-stimulated glucose uptake and transport are reduced after resistance exercise. Furthermore, the applied resistance exercise protocol causes directionally opposite changes of insulin action in two major metabolic pathways, i.e. glucose transport and protein synthesis.     

DHEA improves impaired activation of Akt and PKC ζ/λ‐GLUT4 pathway in skeletal muscle and improves hyperglycaemia in streptozotocin‐induced diabetes rats

Aim: Addition of dehydroepiandrosterone (DHEA) to a cultured skeletal muscle locally synthesizes 5α‐dihydrotestosterone (DHT). It induced activation of glucose metabolism‐related signalling pathway via protein kinase B (Akt) and protein kinase C zeta/lambda (PKC ζ/λ)‐glucose transporter‐4 (GLUT4) proteins. However, such an effect of DHEA in vivo remains unclear. Methods: Using streptozotocin (STZ)‐induced rats with type 1 diabetes mellitus, we tested the hypothesis that a single bout of DHEA injection in the rats improves hyperglycaemia and muscle GLUT4‐regulated signalling pathway. After 1 week of STZ injection (55 mg kg^?1) with male Wistar rats, fasting glucose concentrations were determined in a blood sample taken from the tail vein. Blood glucose levels were then monitored for 180 min after DHEA or sesame oil (control) was injected (n = 10 for each group). Results: Blood glucose levels decreased significantly for 30–150 min after 2 mg DHEA injection in the STZ rats. In the skeletal muscle, expression and translocation of GLUT4 protein, phosphorylation of Akt and PKC ζ/λ, and phosphofructokinase and hexokinase enzyme activities increased significantly by DHEA injection. However, DHEA‐induced improvements in Akt and PKC ζ/λ‐GLUT4 pathways were blocked by a DHT inhibitor. Conclusion: These results suggest that a single bout of DHEA injection can improve hyperglycaemia and activate the glucose metabolism‐related signalling pathway via Akt and PKC ζ/λ‐GLUT4 proteins of skeletal muscles in rats. Moreover, these results show that a DHEA‐induced increase in muscle glucose uptake and utilization might contribute to improvement in hyperglycaemia in type 1 diabetes mellitus.     

Caffeine and theophylline block insulin-stimulated glucose uptake and PKB phosphorylation in rat skeletal muscles

Aim: Caffeine and theophylline inhibit phosphatidylinositol 3-kinase (PI3-kinase) activity and insulin-stimulated protein kinase B (PKB) phosphorylation. Insulin-stimulated glucose uptake involves PI3-kinase/PKB, and the aim of the present study was to test the hypothesis that caffeine and theophylline inhibit insulin-stimulated glucose uptake in skeletal muscles. Methods: Rat epitrochlearis muscles and soleus strips were incubated with insulin and different concentrations of caffeine and theophylline for measurement of glucose uptake, force development and PKB phosphorylation. The effect of caffeine was also investigated in muscles stimulated electrically. Results: Caffeine and theophylline completely blocked insulin-stimulated glucose uptake in both soleus and epitrochlearis muscles at 10 mm . Furthermore, insulin-stimulated PKB Ser⁴⁷³ and Thr³⁰⁸ and GSK-3β Ser⁹ phosphorylation were blocked by caffeine and theophylline. Caffeine reduced and theophylline blocked insulin-stimulated glycogen synthase activation. Caffeine stimulates Ca²⁺ release and force development increased rapidly to 10–20% of maximal tetanic contraction. Dantrolene (25 μm ), a well-known inhibitor of Ca²⁺-release, prevented caffeine-induced force development, but caffeine inhibited insulin-stimulated glucose uptake in the presence of dantrolene. Contraction, like insulin, stimulates glucose uptake via translocation of glucose transporter-4 (GLUT4). Caffeine and theophylline reduced contraction-stimulated glucose uptake by about 50%, whereas contraction-stimulated glycogen breakdown was normal. Conclusion: Caffeine and theophylline block insulin-stimulated glucose uptake independently of Ca²⁺ release, and the likely mechanism is via blockade of insulin-stimulated PI3-kinase/PKB activation. Caffeine and theophylline also reduced contraction-stimulated glucose uptake, which occurs independently of PI3-kinase/PKB, and we hypothesize that caffeine and theophylline also inhibit glucose uptake in skeletal muscles via an additional and hitherto unknown molecule involved in GLUT4 translocation.     

GLUT11, but not GLUT8 or GLUT12, is expressed in human skeletal muscle in a fibre type-specific pattern

Nine novel sugar transporter-like proteins have been discovered in the past 5 years. The mRNA for three of these, the glucose transporters (GLUT) GLUT8, GLUT11 and GLUT12, have been detected in human skeletal muscle. In the present study, we examined the pattern of expression and localization of the GLUT isoforms 8, 11 and 12 in human skeletal muscle using an immunohistochemical approach. Biopsies of human skeletal muscle from sedentary or trained healthy adults, from fetal muscle (24 weeks of gestation), from obese type-2 diabetic subjects, and from patients suffering from polymyositis or amyotrophic lateral sclerosis (ALS) were studied. GLUT8 and 12 immunoreactivity was below detection level in both developing and adult muscle fibres. GLUT11 immunoreactivity, however, was present in slow-twitch muscle fibres, but not in fast twitch fibres. Since, in contrast, GLUT4 was expressed in all investigated muscle fibres, the pattern of expression of GLUT11 differs from that of GLUT4, suggesting a specialized function for GLUT11 with a regulation independent from that of GLUT4. Obesity, type-2 diabetes, training, conditions of de- and reinnervation (ALS) and regeneration (polymyositis) failed to induce GLUT8 or -12 expression. Likewise, the fibre type-dependent pattern of GLUT11 immunoreactivity was unaltered. However, some slow muscle fibres lose their GLUT11 immunoreactivity under regeneration. Our results indicate that GLUT11 immunoreactivity, in contrast to that of GLUT4, is expressed exclusively in slow-twitch muscle fibres and is unaffected by physiological and pathophysiological conditions except in primary myopathy. GLUT8 and GLUT12 do not appear to be of importance in human muscle under physiological and pathophysiological conditions.     

Skeletal muscle buffering capacity is higher in the superficial vastus than in the soleus of spontaneously running rats

Skeletal muscle buffering capacity (βm_titr) was determined in soleus (type I) and superficial vastus (type II) muscles of 16 Long–Evans rats with differing levels of spontaneous activity and in 11 sedentary control rats. βm_titr was 24% higher (P<0.001) in superficial vastus muscle than in soleus muscle (268±50 vs. 216±30 μmol H⁺ g muscle dry wt^-1 pH unit^-1) (mean±SD). There was no relationship between βm_titr and mean weekly running distance amongst spontaneously running rats, nor was βm_titr any greater in these rats than in a group of sedentary control rats. Protein to wet wt ratio was 31% higher (P<0.0001) in the superficial vastus muscle when compared with soleus muscle (22.04±3.74 vs. 16.77±3.00 mg protein, 100 mg wet wt muscle^-1), but there was no relationship between protein to wet wt ratio and running distance. Initial muscle homogenate pH (pH_i) was lower in superficial vastus muscle compared with soleus muscle (6.36±0.25 vs. 6.63±0.16). Running rats had a significantly lower pH_i in both soleus and superficial vastus than sedentary controls. There was an exponential relationship between weekly running distance and pH_i in both the superficial vastus muscle (r=-0.86, P<0.001) and the soleus muscle (r=-0.73, P<0.01). Citrate synthase activity correlated with weekly running distance in superficial vastus muscle (r=0.66, P<0.01) but not in soleus muscle. The results confirm a higher βm_titr in the type II superficial vastus muscle when compared with the predominantly type I soleus muscle. We suggest that this may be partly the result of a higher protein concentration in type II muscle. Future studies measuring βm_titr in mixed muscle (e.g. human vastus lateralis) should report fibre type composition.     

GLUT4 expression at the plasma membrane is related to fibre volume in human skeletal muscle fibres

In this study we examined the relationship between GLUT4 expression at the plasma membrane and muscle fibre size in fibre-typed human muscle fibres by immunocytochemistry and morphometry in order to gain further insight into the regulation of GLUT4 expression. At the site of the plasma membrane, GLUT4 was more abundantly expressed in slow as compared to fast fibres at the same fibre diameter (p < 0.01) and the GLUT4 expression increased with increasing fibre radius independently of fibre type (p < 0.01). The GLUT4 density at the surface of slow fibres of both diabetic and obese was reduced compared to control subjects at the same diameter (p < 0.001). Fast fibres in obese and type 2 diabetic subjects expressed a fibre-volume-dependent GLUT4 expression (p < 0.001), while this did not reach significance in slow fibres (obese p = 0.18 and diabetic p = 0.06). Our results show that increasing fibre volume is associated with increasing GLUT4 expression in both slow and fast fibres. Based on the possible dependency of GLUT4 expression on volume, we hypothesize that the reduced GLUT4 expression in obesity and type 2 diabetes may partly be compensated for by physical activity.     

Skeletal muscle perfusion in electrically induced dynamic exercise in humans

Leg blood flow, blood pressure and metabolic responses were evaluated in six men during incremental one-legged dynamic knee extension exercise tests (no load exercise - 40 W); one performed with voluntary contractions (VOL) and one with electrically induced contractions (EMS). Pulmonary oxygen uptake was the same in both exercise modes, but the ventilatory coefficient was 2–5 L per L O₂ higher in EMS than VOL (P < 0.05). Heart rate and mean arterial pressure were slightly higher with EMS than VOL at all exercise intensities reaching 138 (EMS) and 126 bpm (VOL), as well as 148 (EMS) and 137 mmHg (VOL) at 40 W, respectively (P < 0.05). Leg blood flow, oxygen uptake and conductance were similar in the two exercise modes. At 40 W, mean muscle blood flow was close to 200 (range: 165–220) mL 100 g^-1 min^-1, mean peak muscle oxygen uptake reached 230 mL kg^-1 min^-1, and mean conductance became as high as around 45 mL min^-1 mmHg^-1, and normalized for muscle size and arterial pressure it approached 100 mL min^-1 100 g^-1 100 mmHg^-1. Lactate and ammonia efflux from the leg were higher with EMS than with VOL and the difference became larger with increasing exercise intensity (P < 0.05). Muscle glucose uptake was the same in each exercise mode. Femoral venous K⁺ concentration increased with exercise intensity and was higher with EMS than with VOL, reaching 5.1 (EMS) and 4.7 mmol L^-1 (VOL) at 40 W (P < 0.05). The study demonstrates that electrically induced dynamic exercise is associated with a marked cardiovascular response similar to voluntarily performed exercise and a more pronounced activation of the anaerobic metabolism of the muscle. Furthermore, as the electrically activated muscle group is well defined, the present results confirm that peak muscle blood flow can reach 200–250 mL 100 g^-1 min^-1.     

Over-expression of NYGGF4 (PID1) inhibits glucose transport in skeletal myotubes by blocking the IRS1/PI3K/AKT insulin pathway

IntroductionDefects in insulin-stimulated glucose uptake in muscle are the important early events in the pathogenesis of insulin resistance. NYGGF4 (also named PID1) is a recently discovered gene which is suggested to be associated with obesity-associated insulin resistance. In this study, we aimed to investigate the effects of NYGGF4 on glucose uptake and insulin signaling in rat skeletal muscle cells.MethodsRat L6 myoblasts were transfected with either an empty vector or an NYGGF4-expressing vector and induced to differentiate into mature L6 skeletal myotubes. Glucose uptake was determined by measuring uptake of 2-deoxy-d-[³H] glucose. Immunoblotting was performed to detect the translocation of insulin-sensitive glucose transporter 4 (GLUT4). Immunoblotting was also used to measure phosphorylation and total protein levels of the insulin signaling proteins including insulin receptor (IR), insulin receptor substrate 1 (IRS1), Akt, extracellular signal-regulated kinase 1 and 2 (ERK1/2), p38, and c-Jun-N-terminal kinase (JNK).ResultsNYGGF4 over-expression in L6 skeletal myotubes reduced insulin-stimulated glucose uptake and impaired insulin-stimulated GLUT4 translocation. It also diminished insulin-stimulated tyrosine phosphorylation of IRS1 and serine phosphorylation of Akt without affecting the phosphorylation of IR, ERK1/2, p38, or JNK.ConclusionsOver-expression of NYGGF4 inhibits glucose transport in skeletal myotubes by blocking the IRS1/PI3K/AKT insulin pathway. These observations highlight the potential role of NYGGF4 in glucose homeostasis and the development of insulin resistance in obesity.     

Effects of intensified endurance training on the concentration of Na,K-ATPase and Ca-ATPase in human skeletal muscle

Thirty-nine moderately endurance trained males increased their normal training programme of 2.2 h week^-1 with an average training intensity of 65 % of maximum heart rate (HR_max) to 2.7 h week^-1 and a mean intensity of 78% of HR_max. Performance tests and measurements of the total concentrations of Na,K-ATPase (³H-ouabain binding) and Ca-ATPase, fibre type distribution and fibre area were performed in biopsies from the vastus lateralis muscle before and after increased training. The 6 weeks of training elevated Vo_2max from 54.9 + 3.1 to 58.3±3.0 ml 0₂ min^-1 kg^-1 (P < 0.0001). Exercise time to exhaustion at 86% of Fo_2max (pre-training) increased from 35 ±8 to 61 + 17 min (P < 0.0001). The concentration of Ca-ATPase was unaffected by the intensified training (6.74 ± 1.03 vs. 6.68+ 1.07 nmol g wet wt^-1), but the concentration of Na,K-ATPase increased from 307±43 to 354 + 59 pmol g wet wt ' (P < 0.0001). The relative distribution of FT-fibres was correlated with the concentration of Ca-ATPase (r = 0.72, P < 0.0001). The data support the view that intensive training induces an upregulation of the concentration of skeletal muscle Na,K-ATPase, but no change in the total capacity for reaccumulation of Ca²⁺ into the SR. There was no correlation between the concentrations of Na,K-ATPase, Ca-ATPase and indices of endurance performance.     

No role of interstitial adenosine in insulin-mediated vasodilation

The mechanisms behind the vasodilatory effect of insulin are not fully understood, but nitric oxide plays an important role. We have investigated the possibility that insulin mediates vasodilatation in the human skeletal muscle via an increase in extracellular adenosine concentrations. In eight healthy subjects (H) and in four subjects with a complete, high (C5–C6/7) spinal cord injury (SCI) a hyperinsulinaemic (480 mU min^–1 kg^–1), isoglycaemic clamp was performed. SCI subjects were included as it has been proposed that adenosine and adenine nucleotides may be released from nerve endings in the skeletal muscle. Adenosine concentrations in the extracellular fluid (ECF) of skeletal muscle in the thigh were measured by means of the microdialysis technique. Leg blood flow (LBF) was measured by termodilution. In response to insulin infusion, LBF always increased (P < 0.05) (from 228 ± 25 and 318 ± 18 mL min^–1 to 451 ± 41 and 530 ± 29 mL min^–1, SCI and H, respectively [mean ± SEM]). Concentrations of adenosine in the muscle ECF did not change with infusion of insulin and did not differ between groups (before: 147 ± 55 [SCI] and 207 ± 108 [H] nmol L^–1; during: 160 ± 36 [SCI] and 165 ± 74 [H] nmol L^–1). No significant correlation between concentrations of adenosine and corresponding LBF rates was achieved (LBF=[–0.0936 · Adenosine] + 475. R=–0.092, P=0.22, number of samples=181, number of subjects=12). Conclusion: the mechanism by which insulin mediates an increase in skeletal muscle blood flow is not associated with adenosine in the ECF.     

Dissociation of the effects of training on oxidative metabolism,glucose utilisation and GLUT4 levels in skeletal muscle of streptozotocin-diabetic rats

The effects of long-term, moderate physical exercise on in vivo glucose uptake, levels of two glucose transporter proteins (GLUT1 and GLUT4) and activities of various key enzymes of energy metabolism were measured in skeletal muscle from streptozotocin-diabetic rats. Diabetes (12–16 weeks) reduced the in vivo glucose uptake (glucose metabolic index, GMI) in muscle containing mainly type I fibres by 55% but had no effect in muscles containing mainly type IIa and IIb fibres. GMI was increased in the diabetic white skeletal muscle (mainly type IIb fibres) by more than 120%. In contrast to the complex changes in GMI, GLUT4 levels were reduced in all types of skeletal muscle from diabetic rats with no change in GLUT1 levels. Exercise training had no effects on GMI or the glucose transporter levels. Streptozotocin induced diabetes significantly reduced the oxidative capacity of skeletal muscle assayed as the activities of citrate synthase, succinate dehydrogenase and cytochrome c oxidase. Training increased the activities of oxidative enzymes, with this increase being more prominent in the diabetic animals. The present data indicate that long-term streptozotocin-induced diabetes decreases oxidative metabolic capacity and GLUT4 protein levels in skeletal muscle, but that the changes of glucose transport largely depend on the fibre type composition. Moderate training fully reverses the effect of insulinopenia and hyperglycaemia on muscle oxidative metabolism. In contrast to the previous suggestions, the expression of GLUT4 is not correlated with the capacity of oxidative metabolism in skeletal muscle of streptozotocin-diabetic rats.     

Muscle morphology and performance in master athletes: A systematic review and meta-analyses

IntroductionThe extent to which chronic exercise training preserves age-related decrements in physical function, muscle strength, mass and morphology is unclear. Our aim was to conduct a systematic review of the literature to determine to what extent chronically trained master athletes (strength/power and endurance) preserve levels of physical function, muscle strength, muscle mass and morphology in older age, compared with older and younger controls and young trained individuals.MethodsThe systematic data search included Medline, EMBASE, SPORTDiscus, CINAHL and Web of Science databases.Inclusion criteriai) master athletes mean exercise training duration ≥20 years ii) master athletes mean age of cohort >59 years) iii) at least one measurement of muscle mass/volume/fibre-type morphology and/or strength/physical function.ResultsFifty-five eligible studies were identified. Meta-analyses were carried out on maximal aerobic capacity, maximal voluntary contraction and body composition. Master endurance athletes (42.0 ± 6.6 ml kg⁻¹ min⁻1) exhibited VO_2max values comparable with young healthy controls (43.1 ± 6.8 ml kg⁻¹ min⁻¹, P = .84), greater than older controls (27.1 ± 4.3 ml kg⁻¹ min⁻¹, P < 0.01) and master strength/power athletes (26.5 ± 2.3 mlkg⁻¹ min⁻¹, P < 0.01), and lower than young endurance trained individuals (60.0 ± 5.4 ml kg⁻¹ min⁻¹, P < 0.01). Master strength/power athletes (0.60 (0.28–0.93) P < 0.01) and young controls (0.71 (0.06–1.36) P < 0.05) were significantly stronger compared with the other groups. Body fat% was greater in master endurance athletes than young endurance trained (−4.44% (−8.44 to −0.43) P < 0.05) but lower compared with older controls (7.11% (5.70–8.52) P < 0.01).ConclusionDespite advancing age, this review suggests that chronic exercise training preserves physical function, muscular strength and body fat levels similar to that of young, healthy individuals in an exercise mode-specific manner.     

Effects of training at mild exercise intensities on quadriceps muscle energy metabolism in patients with chronic obstructive pulmonary disease

Aim: To study the effects of physical training at mild intensities on skeletal muscle energy metabolism in eight patients with chronic obstructive pulmonary disease (COPD) and eight paired healthy sedentary subjects. Methods: Energy metabolism of patients and controls vastus lateralis muscle was studied before and after 3 months of cycling training at mild exercises intensities. Results: The total amount of work accomplished was about 4059 ± 336 kJ in patients with COPD and 7531 ± 1693 kJ in control subjects. This work corresponds to a mechanical power set at 65.2 ± 7.5% of the maximum power for patients with COPD and 52 ± 3.3% of the maximum power in control group. Despite this low level of exercise intensities, we observed an improvement in mitochondrial oxidative phosphorylation through the creatine kinase system revealed by the increased apparent K_m for ADP (from 105.5 ± 16.1 to 176.9 ± 26.5 μm , P < 0.05 in the COPD group and from 126.9 ± 16.8 to 177.7 ± 17.0, P > 0.05 in the control group). Meanwhile, maximal mechanical and metabolic power increased significantly from 83.1 ± 7.1 to 91.3 ± 7.4 Watts (P < 0.05) and from 16 ± 0.8 to 18.7 ± 0.98 mL O₂ kg^?1 min^?1 (P < 0.05) only in the COPD group. Conclusion: This study shows that physical training at mild intensity is able to induce comparable changes in skeletal muscles oxidative energy metabolism in patients with COPD and sedentary healthy subjects, but different changes of maximal mechanical and metabolic power.     

GLUT4 activation: thoughts on possible mechanisms

A family of facilitative glucose transporters or GLUTs mediates glucose uptake by cells and tissues. The glucose transporter isoform GLUT4, which is the predominant isoform expressed in mature muscle and fat tissues, is primarily responsible for the increase in glucose uptake in response to insulin stimulation. Recent work in our laboratory suggests that there are two divergent responses initiated by insulin stimulation. The first response involves the recruitment of GLUT4 transporters from intracellular reserves and their subsequent insertion into the plasma membrane. The second pathway results in an increase in the intrinsic activity of the transporters. This review will discuss evidence supporting the divergence of the two pathways regulating glucose uptake and, in particular, evidence for the increased intrinsic activity of GLUT4 in response to insulin stimulation. Inhibitors of p38 mitogen-activated protein kinase (MAPK) affected only the arm leading to the insulin-stimulated activation of GLUT4. This implicates p38 MAPK involvement in the regulation of this pathway. There is further evidence that p38 MAPK is itself recruited to the plasma membrane. The role of the phosphorylation state of the glucose transporter in response to insulin stimulation has been studied and indicates that, contrary to what might be predicted, there is actually a decrease in its phosphorylation at the plasma membrane in response to insulin. The relationship of this change to glucose uptake remains to be established. Other possible mechanisms regulating GLUT4 activity include binding of (+) or (-) modulators of its function.     

Increase in the proportion of fast-twitch muscle fibres by sprint training in males

Fifteen male physical education students were studied. The subjects trained for 4–6 weeks, 2–3 days per week, on a mechanically braked bicycle ergometer. A training session consisted of repeated 30-s ‘all-out’ sprints on a Wingate bicycle ergometer, on which the brake band of the flywheel was loaded with 75 g kg^-1 body wt, with rest periods of 15–20 min between consecutive sprints. Thigh muscle biopsies were taken before and after the training period and were analysed for fibre types using a myofibrillar ATPase stain. The proportion of type I fibres decreased from 57 to 48% (P < 0.05) and type IIA fibres increased from 32 to 38% (P < 0.05). This study indicates that it is possible to achieve a fibre type transformation with high-intensity training. The effect of two-legged ‘sprint’ training on muscle fibre type composition may be related to a changed pattern of muscle fibre activation (e.g. an increased stimulation frequency). A change in fibre activation frequency may induce an increased synthesis of type II fibre myosin (fast myosin). Hormonal influences such as enhanced adrenergic stimulation of the muscle fibres cannot be excluded as a contributing factor, however.