The “muscular variant” of Pompe disease: Clinical,biochemical and histologic characteristics

We report on a 2-yr-old boy with progressive muscular weakness and respiratory failure. There was no clinical evidence of heart muscle involvement. Autopsy showed marked intralysosomal glycogen deposition in skeletal muscle and liver with no histological evidence of glycogen deposition in cardiac muscle. The activity of the lysosomal enzyme α-1,4-glucosidase was deficient in skin fibroblasts, skeletal muscle, cardiac muscle, and liver; however, the enzymatic activity in peripheral blood leukocytes was in the low normal range. The child's mother had normal enzymatic activity in leukocytes but heterozygote levels in skin fibroblasts.     

Exercise Increases Ca2+–Calmodulin-Dependent Protein Kinase II Activity in Human Skeletal Muscle

There is evidence in rodents that Ca²⁺-calmodulin-dependent protein kinase II (CaMKII) activity is higher in contracting skeletal muscle, and this kinase may regulate skeletal muscle function and metabolism during exercise. To investigate the effect of exercise on CaMKII in human skeletal muscle, healthy men (   n = 8  ) performed cycle ergometer exercise for 40 min at 76 ± 1 % peak pulmonary O₂ uptake (_O2peak), with skeletal muscle samples taken at rest and after 5 and 40 min of exercise. CaMKII expression and activities were examined by immunoblotting and in vitro kinase assays, respectively. There were no differences in maximal (+ Ca²⁺, CaM) CaMKII activity during exercise compared with rest. Autonomous (- Ca²⁺, CaM) CaMKII activity was 9 ± 1 % of maximal at rest, remained unchanged at 5 min, and increased to 17 ± 1 % (   P < 0.01  ) at 40 min. CaMKII autophosphorylation at Thr²⁸⁷ was 50-70 % higher during exercise, with no differences in CaMKII expression. The effect of maximal aerobic exercise on CaMKII was also examined (   n = 9  ), with 0.7- to 1.5-fold increases in autonomous CaMKII activity, but no change in maximal CaMKII activity. CaMKIV was not detected in human skeletal muscle. In summary, exercise increases the activity of CaMKII in skeletal muscle, suggesting that it may have a role in regulating skeletal muscle function and metabolism during exercise in humans.     

Relationship between muscle fibre composition,glucose transporter protein 4 and exercise training: possible consequences in non‐insulin‐dependent diabetes mellitus

Skeletal muscle is composed of different fibre types, which differ in contractile as well as in metabolic properties. The myosin molecule, which exists in several different isoforms, is of major importance in determining the contractile properties of the muscle cell. The plasticity of skeletal muscle is reflected in this tissue’s adaptability to changes in the functional demand. In both rats and humans, a decrease in activity level will in most cases change the muscle fibre composition towards faster myosin isoforms and an increase in activity level (such as seen with exercise training) will induce an increase in slower myosin isoforms. The glucose transporter protein 4 (GLUT4), which is the major insulin regulatable glucose transporter in mammalian skeletal muscle, is found in larger amounts in slow muscle fibres compared with fast muscle fibres. An increase in activity level will increase the GLUT4 protein expression and a decrease in activity level will in most cases decrease GLUT4. Thus, there seems to be some kind of relationship between the muscle fibre type and GLUT4. However, the main factor regulating both the GLUT4 protein expression and the muscle fibre composition seems to be the activity level of the muscle fibre. Patients suffering from non‐insulin‐dependent diabetes mellitus (NIDDM) are insulin resistant in their skeletal muscles but are generally normal when it comes to skeletal muscle fibre composition and the GLUT4 protein expression. There is good evidence that exercise training beneficially impacts on insulin sensitivity in healthy individuals and in patients with type II diabetes. An increase in the GLUT4 protein expression in skeletal muscle may at least partly explain this effect of training.     

Ca2+–calmodulin-dependent protein kinase expression and signalling in skeletal muscle during exercise

Ca²⁺ signalling is proposed to play an important role in skeletal muscle function during exercise. Here, we examined the expression of multifunctional Ca²⁺–calmodulin-dependent protein kinases (CaMK) in human skeletal muscle and show that CaMKII and CaMKK, but not CaMKI or CaMKIV, are expressed. Furthermore, the effect of exercise duration and intensity on skeletal muscle CaMKII activity and phosphorylation of downstream targets was examined. Eight healthy men exercised at ∼67% of peak pulmonary O₂ uptake     with muscle samples taken at rest and after 1, 10, 30, 60 and 90 min of exercise. Ten other men exercised for three consecutive 10 min bouts at 35%, 60% and 85%     with muscle samples taken at rest, at the end of each interval and 30 min post-exercise. There was a rapid and transient increase in autonomous CaMKII activity and CaMKII phosphorylation at Thr²⁸⁷ in skeletal muscle during exercise. Furthermore, the phosphorylation of phospholamban (PLN) at Thr¹⁷, which was identified as a CaMKII substrate in skeletal muscle, was rapidly (< 1 min) increased by exercise, and remained phosphorylated 5-fold above basal level during 90 min of exercise. The phosphorylation of serum response factor at Ser¹⁰³, a putative CaMKII substrate, was higher after 30 min of exercise. PLN phosphorylation at Thr¹⁷ was higher with increasing exercise intensities. These data indicate that CaMKII is the major multifunctional CaMK in skeletal muscle and its activation occurs rapidly and is sustained during continuous exercise, with the activation being greater during intense exercise.     

Oestrogen receptor β is expressed in adult human skeletal muscle both at the mRNA and protein level

Aim: There are two known oestrogen receptors (ER), oestrogen receptor α (ERα) and the recently cloned oestrogen receptor β (ERβ). ERα mRNA has been detected in mouse, rat, bovine and human skeletal muscle. ERβ mRNA has been detected in bovine skeletal muscle. To our knowledge, no study has investigated the expression of oestrogen receptor β in human skeletal muscle. Therefore, the primary aim of the present investigation was to study ERβ mRNA and protein expression in human skeletal muscle. In addition the ERα expression was also studied. Methods: Muscle biopsies were taken from vastus lateralis in six healthy adults (three women and three men). mRNA expression was detected with real‐time PCR (TaqMan) and protein localization by immunohistochemistry. Results: A clear expression of ERα and ERβ mRNA was seen in skeletal muscle in all subjects. The ERα mRNA expression was 180 fold higher compared with that of ERβ mRNA. Immunohistochemistry demonstrated positive staining for ERβ, but not for ERα, with localization to the nuclei of skeletal muscle fibres. On average, 70% of all nuclei were ERβ‐positive. Conclusion: The present study shows for the first time ERβ mRNA and protein expression in human skeletal muscle tissue in both males and females.     

Neonatal hyper- and hypothyroidism alter the myoglobin gene expression program in adulthood

Myoglobin acts as an oxygen store and a reactive oxygen species acceptor in muscles. We examined myoglobin mRNA in rat cardiac ventricle and skeletal muscles during the first 42 days of life and the impact of transient neonatal hypo- and hyperthyroidism on the myoglobin gene expression pattern. Cardiac ventricle and skeletal muscles of Wistar rats at 7-42 days of life were quickly removed, and myoglobin mRNA was determined by Northern blot analysis. Rats were treated with propylthiouracil (5-10 mg/100 g) and triiodothyronine (0.5-50 µg/100 g) for 5, 15, or 30 days after birth to induce hypo- and hyperthyroidism and euthanized either just after treatment or at 90 days. During postnatal (P) days 7-28, the ventricle myoglobin mRNA remained unchanged, but it gradually increased in skeletal muscle (12-fold). Triiodothyronine treatment, from days P0-P5, increased the skeletal muscle myoglobin mRNA 1.5- to 4.5-fold; a 2.5-fold increase was observed in ventricle muscle, but only when triiodothyronine treatment was extended to day P15. Conversely, hypothyroidism at P5 markedly decreased (60%) ventricular myoglobin mRNA. Moreover, transient hyperthyroidism in the neonatal period increased ventricle myoglobin mRNA (2-fold), and decreased heart rate (5%), fast muscle myoglobin mRNA (30%) and body weight (20%) in adulthood. Transient hypothyroidism in the neonatal period also permanently decreased fast muscle myoglobin mRNA (30%) and body weight (14%). These results indicated that changes in triiodothyronine supply in the neonatal period alter the myoglobin expression program in ventricle and skeletal muscle, leading to specific physiological repercussions and alterations in other parameters in adulthood.     

Desmin‐related myopathies in mice and man

Desmin, the main intermediate filament (IF) protein in skeletal and heart muscle cells, is of great importance as a part of the cytoskeleton. The IFs surround and interlink myofibrils, and connect the peripheral myofibrils with the sarcolemma. In myotendinous junctions and neuromuscular junctions of skeletal muscle fibres, desmin is enriched. In the heart, desmin is increased at intercalated discs, the attachment between cardiomyocytes, and it is the main component in Purkinje fibres of the conduction system. Desmin is the first muscle‐specific protein to appear during myogenesis. Nevertheless, lack of desmin, as shown from experiments with desmin knockout (K/O) mice, does not influence myogenesis or myofibrillogenesis. However, the desmin knock‐out mice postnatally develop a cardiomyopathy and a muscle dystrophy in highly used skeletal muscles. In other skeletal muscles the organization of myofibrils is remarkably unaffected. Thus, the main consequence of the lack of desmin is that the muscle fibres become more susceptible to damage. The loss of membrane integrity leads to a dystrophic process, with degeneration and fibrosis. In the heart cardiac failure develops, whereas in affected skeletal muscles regenerative attempts are seen. In humans, accumulations of desmin have been a hallmark for presumptive desmin myopathies. Recent investigations have shown that some families with such a myopathy have a defect in the gene coding for αB‐crystallin, whereas others have mutations in the desmin gene. Typical features of these patients are cardiac affections and muscle weakness. Thus, mutations in the desmin gene is pathogenic for a distinct type of muscle disorder.     

New evidence for similarities in excitation–contraction coupling in skeletal and cardiac muscle

This review describes several new experimental observations indicating that some of the differences thought to distinguish activation of contraction in skeletal and cardiac muscle may be in fact much less profound than are currently considered. Three such areas are considered in particular. First, it now appears that activation of the elementary units of Ca²⁺ release from the sarcoplasmic reticulum (`Ca<sup>2+</sup>sparks') in skeletal muscle may occur not only as the result of voltage activation but also of Ca<sup>2+</sup> activation in a process very much like Ca<sup>2+</sup>-induced Ca<sup>2+</sup> release (CICR) in cardiac muscle. Second, there is new evidence that activation of contraction in cardiac muscle may be partly reliant on a voltage-sensitive release mechanism (VSRM) similar to that in skeletal muscle. Third, digitalis binds to a high affinity site on the cardiac sarcoplasmic reticulum Ca<sup>2+</sup> release channel (ryanodine receptor RyR) causing an increase in single channel open probability which could contribute to its positive inotropic action; although mammalian skeletal muscle does not appear to share this sensitivity to cardiac glycosides, amphibian skeletal muscle has both cardiac and skeletal isoforms of the channel and does indeed demonstrate a positive inotropic action in response to digitalis. These results raise the possibility that several differences thought to represent `fundamental' distinctions between the two muscle types and how they generate and regulate contraction, as well as pharmacological sensitivities, may be more similar than are currently considered.     

Exercise‐induced muscle damage and inflammation: fact or fiction?

Physical exercise is necessary for maintaining normal function of skeletal muscle. The mechanisms governing normal muscle function and maintenance are vastly unknown but synergistic function of hormones, neurosignalling, growth factors, cytokines and other factors, is undoubtedly important. Because of the complex interaction among these systems the lack of complete understanding of muscle function is not surprising. The purpose of exercise‐induced changes in muscle cell function is to adapt the tissue to a demand of increased physical work capacity. Some of the approaches used to investigate changes in skeletal muscle cell function are exercise and electrical stimulation in animals and human models and isolated animal muscle. From these models, it has been concluded that during physical exercise, in an intensity and duration dependent manner, skeletal muscle is damaged and subsequently inflamed. The purpose of the inflammation would be to repair the exercise‐induced damage. Because of the design and methods used in a majority of these studies, concerns must be raised, and the question asked whether the paradigm of exercise‐induced muscle inflammation in fact is fiction. In a majority of conducted studies, a non‐exercising control group is lacking and because of the invasive nature of the sampling methods used to study inflammation it does not appear impossible that observed inflammatory events in human skeletal muscle after physical exercise are methodoligical artefacts.     

Metabolic responses in feline “red” and “white” skeletal muscle to shock and ischemia

In order to investigate possible differences in the reaction to hypoxic conditions between “red” and “white” skeletal muscle, cats were subjected to a 2 h period of either hemorrhagic shock or hind limb tourniquet ischemia, and the hypoxia induced changes were studied in the soleus and lateral gastrocnemius muscles. Muscle biopsies were analysed for ATP, CP, glucose, G 6–P and lactate. Using microelectrodes, the resting membrane potential was repeatedly measured. Both experimental models resulted in increased tissue lactate levels and a successive decrease in the membrane potential of both muscles studied. No reduction of the high energy phosphagen content (ATP+CP) occurred in any of the muscles during shock. The tourniquet ischemia resulted in a 40% reduction of the ATP+CP content in the soleus muscle, whereas in the gastrocnemius muscle no significant reduction occurred. A significant correlation was found between the tissue lactate content and the membrane potential under both conditions and in both muscles studied. It is concluded that “red” muscles are more susceptible to metabolic derangement than “white” muscles during total ischemia, whereas during hypovolemia “red” muscles appear to be protected from early hypoxic damage, probably due to a redistribution of skeletal muscle blood flow.     

Activities of key enzymes in the energy metabolism of human myocardial and skeletal muscle

Activities of total creatine kinase (CK), its isoenzyme MB (CK-MB), total lactate dehydrogenase (LD) and its isoenzyme LD1, phosphofructokinase (PFK), aspartate aminotransferase (ASAT) and citrate synthase (CS) were determined in skeletal muscle biopsies obtained from physically trained and untrained men and in myocardial biopsies from patients subjected to open heart surgery because of valve disease. The LD1, ASAT and CS activities were higher in trained than in untrained skeletal muscle and still higher in heart muscle than in either trained or untrained skeletal muscle. The CK-MB activity was higher in trained than untrained skeletal muscle and the myocardial CK-MB activity was similar to that in trained skeletal muscle. Total CK activity was slightly lower in trained than in untrained skeletal muscle and the myocardial CK activity was approximately one third of the skeletal muscle CK. Both the PFK and the total LD activity was of similar magnitude in the different muscle types. In conclusion, as estimated by enzyme activities, the oxidative capacity is 2-3 times larger in myocardial than in skeletal muscle, while the glycolytic capacity as estimated by PFK appears to be the same.     

骨骼肌卫星细胞生长因子与运动训练的关系

背景：大运动量训练可以导致骨骼肌组织微细结构的损伤性变化, 而骨骼肌卫星细胞的激活、增殖与分化和肌肉组织损伤的修复有密切关系。 目的：文章从训练导致肌肉组织结构性损伤需要修复的客观实际出发,提出运动后骨骼肌结构的修复与骨骼肌卫星细胞生长因子之间存在某种依赖关系。 方法：由第一作者通过计算机网络检索中国期刊全文数据库(CNKI)和Medline数据库(2000/2010),检索词分别为“骨骼肌卫星细胞,生长因子,运动训练,骨骼肌超微结构”和“Skeletal muscle satellite cells,exercise,growth factor”。 共检索到97篇文章,按纳入和排除标准对文献进行筛选,共纳入23篇文章。从运动后骨骼肌组织修复与骨骼肌卫星细胞生长因子的激活作用机制进行总结,对两者间的联系进行分析。 结果与结论：大强度训练可以导致骨骼肌组织的损伤,而卫星细胞是运动后恢复期骨骼肌修复的关键,其生长因子也与训练方式等因素有关。目前在骨骼肌卫星细胞的生长因子与运动训练之间的联系还缺乏足够的认识与研究。     

O‐GlcNAcylation as a regulator of the functional and structural properties of the sarcomere in skeletal muscle: An update review

Although the O‐GlcNAcylation process was discovered in 1984, its potential role in the physiology and physiopathology of skeletal muscle only emerged 20 years later. An increasing number of publications strongly support a key role of O‐GlcNAcylation in the modulation of important cellular processes which are essential for skeletal muscle functions. Indeed, over a thousand of O‐GlcNAcylated proteins have been identified within skeletal muscle since 2004, which belong to various classes of proteins, including sarcomeric proteins. In this review, we focused on these myofibrillar proteins, including contractile and structural proteins. Because of the modification of motor and regulatory proteins, the regulatory myosin light chain (MLC2) is related to several reports that support a key role of O‐GlcNAcylation in the fine modulation of calcium activation parameters of skeletal muscle fibres, depending on muscle phenotype and muscle work. In addition, another key function of O‐GlcNAcylation has recently emerged in the regulation of organization and reorganization of the sarcomere. Altogether, this data support a key role of O‐GlcNAcylation in the homeostasis of sarcomeric cytoskeleton, known to be disturbed in many related muscle disorders.     

ARNT调控低氧通路促进小鼠骨骼肌再生的实验研究

目的　探索芳香烃受体核转运子（aryl hydrocarbon receptor nuclear translocator,ARNT）对骨骼肌再生的调控作用,为提高老龄人口骨骼肌再生能力提供方向。 方法　构建小鼠骨骼肌冰冻损伤模型,观察幼龄鼠与老龄鼠、骨骼肌特异性ARNT基因敲除小鼠与野生鼠、加入低氧通路激活剂（ML228）与DMSO老龄鼠间骨骼肌再生能力差别;分析ARNT、低氧通路、肌再生因子表达含量及小鼠下肢血流差异。 结果　衰老导致骨骼肌再生能力减弱;敲除ARNT基因后,小鼠骨骼肌的再生能力显著下降,低氧通路因子及相关基因表达下调;ML228可使受损的骨骼肌再生能力得到恢复。 结论　衰老引起的ARNT含量下降抑制低氧通路是导致老龄骨骼肌再生能力降低的主要原因。低氧通路激活剂可改善受损骨骼肌的再生能力,有望成为药物重塑衰老骨骼肌再生能力的新靶点。     

Adenosine and nitric oxide in exercise‐induced human skeletal muscle vasodilatation

The vasoactive substances adenosine and nitric oxide (NO) are credible candidates in the local regulation of skeletal muscle blood flow. Adenosine and NO have both been shown to increase in skeletal muscle cells and interstitial fluid during exercise and the enzymes responsible for their formation, AMP 5′‐nucleotidase and NO synthase (NOS), have been shown to be activated upon muscle contraction. In vitro as well as in vivo evidence suggest that the contraction‐induced increase in interstitial adenosine concentration largely stems from extracellular formation via the membrane‐bound ecto‐form of AMP 5′‐nucleotidase. It remains unclear whether the exercise‐induced NO formation in muscle originates from endothelial NOS in the microvascular endothelium, or from neuronal NOS (nNOS) in nerve cells and muscle fibres. Functional evidence for the role of adenosine in muscle blood flow control stems from studies using adenosine receptor agonists and antagonsits, adenosine deaminase or adenosine uptake inhibitors. The majority of these studies have been performed on laboratory animals and, although the results show some discrepancy, the majority of studies indicate that adenosine does participate in the regulation of muscle blood flow. In humans, evidence is lacking. The role of NO in the regulation of skeletal muscle blood flow has mainly been studied using NOS inhibitors. Despite a large number of studies in this area, the role of NO for the contraction‐induced increase in skeletal muscle blood flow is uncertain. The majority, but not all, human and animal studies show that, whereas blockade of NOS reduces muscle blood flow at rest and in recovery from exercise, there is no effect on the exercise‐induced increase in muscle perfusion. Conclusive evidence for the mechanisms underlying the precise regulation of the multiphased increase in skeletal muscle blood flow during exercise and the role and potency of various vasoactive substances, remain missing.     

Both smooth and skeletal muscle precursors are present in foetal mouse oesophagus and they follow different differentiation pathways.

Muscularis externa of mouse oesophagus is composed of two skeletal muscle layers in the adult. Unlike rest of skeletal muscle in the body, the oesophageal skeletal muscle in the mouse has been proposed to be derived from fully differentiated smooth muscle cells by transdifferentiation during later foetal and early postnatal development (Patapoutian et al. [1995] Science 270:1818-1821). Here we characterised the nature of cells in muscularis externa of the mouse oesophagus by ultrastructural and immunoctyochemical analyses. The presence of differentiated skeletal muscle cells identified by positive staining for skeletal muscle specific myosin heavy chain became first apparent in the outer layer of cranial oesophagus at 14 days gestation. The transient expression of smooth muscle type alpha-actin in mouse oesophageal muscle was also apparent during foetal development. This isoform, however, was not smooth muscle specific during early development as it was also detected in foetal skeletal muscles. Compared with oesophagus, the suppression of this smooth muscle type alpha-actin during foetal development was faster in non-oesophageal skeletal muscle cells. The development of skeletal muscle in oesophagus showed a cranial to caudal and an outer layer to inner layer progression. During early foetal development, mouse oesophagus is composed of undifferentiated mesenchymal cells that formed cell clusters. Two types of cells with different staining densities could be distinguished within these cell clusters by electron microscopy. The centrally located pale staining cells gave rise to skeletal muscle cells while the peripherally positioned dense staining cells gave rise to smooth muscle cells, indicating the existence of both skeletal and smooth muscle cell precursors in mouse oesophagus during early foetal development. Further development showed an increase in the proportion of skeletal muscle cells and a decrease in size and number of the smooth muscle type cells. Apart from decrease in cell size, some other morphological features of smooth muscle cell degeneration were also observed during later foetal and early neonatal development. No smooth muscle cells undergoing transdifferentiation were observed. Both immunochemical and ultrastructural observations, thus, demonstrated the presence of skeletal muscle cells in early foetal oesophagus. It is concluded that the transient appearance of smooth muscle cells may provide a scaffold for the laying down of skeletal muscle layers in mouse oesophagus, the final disappearance of which may be triggered by lack of smooth muscle innervation.     

Sequestosome‐1 (p62) expression reveals chaperone‐assisted selective autophagy in immune‐mediated necrotizing myopathies

Diffuse myofiber necrosis in the context of inflammatory myopathy is the hallmark of immune‐mediated necrotizing myopathy (IMNM). We have previously shown that skeletal muscle fibers of IMNM patients may display nonrimmed vacuoles and sarcoplasmic irregularities. The dysfunctional chaperone activity has been linked to the defective assembly of skeletal muscle proteins and their degradation via lysosomes, autophagy and the proteasomal machinery. This study was undertaken to highlight a chaperone‐assisted selective autophagy (CASA) pathway, functionally involved in protein homeostasis, cell stress and the immune response in skeletal muscle of IMNM patients. Skeletal muscle biopsies from 54 IMNM patients were analyzed by immunostaining, as well as by qPCR. Eight biopsies of sIBM patients served as pathological controls, and eight biopsies of nondisease control subjects were included. Alteration of autophagy was detectable in all IMNM biopsy samples highlighted via a diffuse sarcoplasmic staining pattern by p62 and LC3 independent of vacuoles. This pattern was at variance with the coarse focal staining pattern mostly confined to rimmed vacuoles in sIBM. Colocalization of p62 with the chaperone proteins HSP70 and αB‐crystalline points to the specific targeting of misfolded proteins to the CASA machinery. Bcl2‐associated athanogene 3 (BAG3) positivity of these fibers emphasizes the selectivity of autophagy processes and these fibers also express MHC class I sarcolemma. Expression of genes involved in autophagy and endoplasmic reticulum (ER) stress pathways studied here is significantly upregulated in IMNM. We highlight that vacuoles without sarcolemmal features may arise in IMNM muscle biopsies, and they must not be confounded with sIBM‐specific vacuoles. Further, we show the activation of selective autophagy and emphasize the role of chaperones in this context. CASA occurs in IMNM muscle, and specific molecular pathways of autophagy differ from the ones in sIBM, with p62 as a unique identifier of this process.     

Pro‐ and macroglycogenolysis in contracting rat skeletal muscle

Glycogen is present in skeletal muscle in smaller acid‐insoluble proglycogen particles and larger acid‐soluble macroglycogen particles. The present study was designed to investigate the relative contribution of pro‐ and macroglycogen to glycogenolysis during muscle contractions. Rats were subjected to a glycogen‐depleting exercise bout and refed with either a carbohydrate‐rich or fat‐rich diet, resulting in widely different muscle glycogen contents. The following day, isolated hindlimbs were perfused and electrically stimulated to contract for 10 min. Pre‐ and postcontraction muscle samples of soleus, white and red gastrocnemius were analysed for pro‐ and macroglycogen. Contractions caused significant reductions in both pro‐ and macroglycogen in all glycogen groups and muscle types. In glycogen‐supercompensated gastrocnemius muscles, the relative utilization of macroglycogen was significantly higher than the relative utilization of proglycogen. In muscles with normal to low initial glycogen contents, proglycogen was much more abundant than macroglycogen and therefore contributed more to glycogenolysis in absolute numbers. In conclusion, both proglycogen and macroglycogen are suitable substrates during skeletal muscle contractions, although macroglycogen, when amply available, seems to be more easily broken down. This may provide an explanation for the dependence of the glycogenolytic rate on the total muscle glycogen content.     

Effects of high‐intensity intermittent swimming on PGC‐1α protein expression in rat skeletal muscle

Aim: The aim of the present investigation was to elucidate the effects of exercise intensity on exercise‐induced expression of peroxisome proliferator‐activated receptor γ coactivator‐1α (PGC‐1α) protein in rat skeletal muscle. Methods: We measured PGC‐1α content in the skeletal muscles of male Sprague–Dawley rats (age: 5–6 weeks old; body weight: 150–170 g) after a single session of high‐intensity intermittent exercise (HIE) or low‐intensity prolonged swimming exercise (LIE). During HIE, the rats swam for fourteen 20‐s periods carrying a weight (14% of body weight), and the periods of swimming were separated by a 10‐s pause. LIE rats swam with no load for 6 h in two 3‐h sessions, separated by 45 min of rest. Results: After HIE, the PGC‐1α protein content in rat epitrochlearis muscle had increased by 126, 140 and 126% at 2, 6 and 18 h, respectively, compared with that of the age‐matched sedentary control rats’ muscle. Immediately, 6 and 18‐h after LIE, the PGC‐1α protein content in the muscle was significantly elevated by 84, 95 and 67% respectively. The PGC‐1α protein content observed 6 h after HIE tended to be higher than that observed after LIE. However, there was no statistically significant difference between the two values (P = 0.12). Conclusion: The present investigation suggests that irrespective of the intensity of the exercise, PGC‐1α protein content in rat skeletal muscle increases to a comparable level when stimuli induced by different protocols are saturated. Further, HIE is a potent stimulus for enhancing the expression of PGC‐1αprotein, which may induce mitochondrial biogenesis in exercise‐activated skeletal muscle.     

Evidence against a sexual dimorphism in glucose and fatty acid metabolism in skeletal muscle cultures from age‐matched men and post‐menopausal women

Aim: In vivo whole body differences in glucose/lipid metabolism exist between men and women. Thus, we tested the hypothesis that intrinsic sex differences exist in skeletal muscle gene expression and glucose/lipid metabolism using cultured myotubes. Methods: Myotube cultures were prepared for gene expression and metabolic studies from vastus lateralis skeletal muscle biopsies obtained from age‐matched men (n = 11; 59 ± 2 years) and post‐menopausal women (n = 10; 60 ± 1 years). Results: mRNA expression of several genes involved in glucose and lipid metabolism was higher in skeletal muscle biopsies from female vs. male donors, but unaltered between the sexes in cultured myotubes. Basal and insulin‐stimulated glucose uptake, as well as glucose incorporation into glycogen, was similar in myotube cultures derived from male vs. female donors. In males vs. females, insulin increased glucose uptake (1.3 ± 0.1 vs. 1.5 ± 0.1‐fold respectively) and incorporation into glycogen (2.3 ± 0.3 vs. 2.0 ± 0.3‐fold respectively) to the same extent. Basal fatty acid oxidation and rate of uptake/accumulation was similar between sexes. In response to the 5′AMP‐activated protein kinase activator AICAR, lipid oxidation was increased to the same extent in myotubes established from male vs. female donors (1.6 ± 0.6 vs. 2.0 ± 0.3‐fold respectively). Moreover, the AICAR‐induced rate of uptake/accumulation was similar between sexes. Conclusion: Differences in metabolic parameters and gene expression profiles between age‐matched men and post‐menopausal women noted in vivo are not observed in cultured human skeletal muscle cells. Thus, the sexual dimorphism in glucose and lipid metabolism is likely a consequence of systemic whole body factors, rather than intrinsic differences in the skeletal muscle proper.