glycogen and Muscular-Atrophy

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.

Topics: Administration, Oral; Anabolic Agents; Athletic Performance; Creatine; Exercise; Gene Expression Regulation; Glycogen; Humans; Hypoglycemic Agents; Insulin; Insulin Resistance; Muscle Contraction; Muscle Proteins; Muscle, Skeletal; Muscular Atrophy

Our purpose is to summarize the major effects of space travel on skeletal muscle with particular emphasis on factors that alter function. The primary deleterious changes are muscle atrophy and the associated decline in peak force and power. Studies on both rats and humans demonstrate a rapid loss of cell mass with microgravity. In rats, a reduction in muscle mass of up to 37% was observed within 1 week. For both species, the antigravity soleus muscle showed greater atrophy than the fast-twitch gastrocnemius. However, in the rat, the slow type I fibers atrophied more than the fast type II fibers, while in humans, the fast type II fibers were at least as susceptible to space-induced atrophy as the slow fiber type. Space flight also resulted in a significant decline in peak force. For example, the maximal voluntary contraction of the human plantar flexor muscles declined by 20-48% following 6 months in space, while a 21% decline in the peak force of the soleus type I fibers was observed after a 17-day shuttle flight. The reduced force can be attributed both to muscle atrophy and to a selective loss of contractile protein. The former was the primary cause because, when force was expressed per cross-sectional area (kNm(-2)), the human fast type II and slow type I fibers of the soleus showed no change and a 4% decrease in force, respectively. Microgravity has been shown to increase the shortening velocity of the plantar flexors. This increase can be attributed both to an elevated maximal shortening velocity (V(0)) of the individual slow and fast fibers and to an increased expression of fibers containing fast myosin. Although the cause of the former is unknown, it might result from the selective loss of the thin filament actin and an associated decline in the internal drag during cross-bridge cycling. Despite the increase in fiber V(0), peak power of the slow type I fiber was reduced following space flight. The decreased power was a direct result of the reduced force caused by the fiber atrophy. In addition to fiber atrophy and the loss of force and power, weightlessness reduces the ability of the slow soleus to oxidize fats and increases the utilization of muscle glycogen, at least in rats. This substrate change leads to an increased rate of fatigue. Finally, with return to the 1g environment of earth, rat studies have shown an increased occurrence of eccentric contraction-induced fiber damage. The damage occurs with re-loading and not in-flight, but the etiolo

Topics: Animals; Astronauts; Contractile Proteins; Glycogen; Humans; Lactic Acid; Microscopy, Electron; Muscle Contraction; Muscle Fatigue; Muscle Fibers, Skeletal; Muscle, Skeletal; Muscular Atrophy; Space Flight; Weightlessness

Clinical, neurophysiological, morphological and biochemical investigations were performed in 2 patients with the adult form of glycogenosis II and related to the findings of 58 well-documented cases published in the literature. According to these findings three types can be distinguished from each other. The first one is characterized by an involvement of the limb-girdle muscles only. The second type shows the same pattern with additional progressive insufficiency of the respiratory muscles. The third type presents with weakness of the respiratory muscles without any other severe muscle involvement. Our case 1 can be related to the first, our case 2 to the second type. EMG-studies in case 1 showed myopathic changes and myotonic discharges without clinical signs of myotonia. A myotonic pattern was described in one third of the published cases. In case 2 neurogenic changes as well as in 4 cases in the literature were found. The muscle biopsy is the diagnostic clue in the differential diagnosis of progressive myopathy in the adult. Patients with glycogenosis II show glycogen storage specially in type I-fibres. The enzyme defect can be confirmed biochemically in muscle tissue or cultured fibroblasts. Various therapeutic concepts have been tried in patients with glycogenosis II but most of them remain disappointing. A diet with a low carbohydrate and a high protein proportion was observed to be of some benefit. In patients with respiratory muscle involvement artificial ventilation support showed a positive effect on the general condition for some time.

Topics: Adult; Biopsy; Glycogen; Glycogen Storage Disease Type II; Humans; Male; Microscopy, Electron; Muscles; Muscular Atrophy; Neuromuscular Diseases; Reaction Time; Synaptic Transmission; Tibial Nerve

Phosphorylase b kinase deficiency affecting muscle has been observed infrequently in children with weakness and hepatomegaly, and in 2 adults with cramps on exertion. We observed 2 additional adults with phosphorylase b kinase deficiency: Patient 1, aged 58, had progressive, predominantly distal weakness since age 46 but no cramps on exertion; Patient 2, aged 26, had cramps on exertion since age 6 but no weakness. Lactate production on ischemic exercise was impaired only in Patient 1. The serum creatine kinase level was elevated in both. Muscle specimens showed focal glycogen excess in both, and a necrotizing myopathy and mild denervation atrophy in Patient 1. Muscle phosphorylase b kinase activity was 0.5% and 8.9% of the lowest control value in Patients 1 and 2, respectively; erythrocyte phosphorylase b kinase activity was normal in both; liver phosphorylase b kinase activity, measured in Patient 1, was also normal. Other glycolytic enzymes in muscle were preserved in both.

Topics: Adult; Creatine Kinase; Glycogen; Humans; Male; Middle Aged; Muscle Cramp; Muscle Proteins; Muscles; Muscular Atrophy; Phosphorylase Kinase; Physical Exertion; Syndrome; X Chromosome

Topics: Adolescent; Biopsy; Child; Child, Preschool; Cytoplasm; Diet Therapy; Electromyography; Female; Glycogen; Humans; Infant; Lipid Metabolism; Male; Mitochondria, Muscle; Motor Neurons; Muscles; Muscular Atrophy; Muscular Diseases; Muscular Dystrophies; Necrosis; Nervous System Diseases; Obesity; Obesity Hypoventilation Syndrome

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 approximately 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.

Topics: Administration, Oral; Adult; Casts, Surgical; Creatine; Double-Blind Method; Female; Glucose Transporter Type 4; Glycogen; Humans; Immobilization; Leg; Male; Monosaccharide Transport Proteins; Muscle Proteins; Muscle, Skeletal; Muscular Atrophy; Physical Education and Training; Weight Lifting

Both quercetin and leucine have been shown to exert moderately beneficial effects in preventing muscle atrophy induced by cancers or chemotherapy. However, the combined effects of quercetin and leucine, as well as the possible underlying mechanisms against cisplatin (CDDP)-induced muscle atrophy and cancer-related fatigue (CRF) remain unclear. To investigate the issues, male BALB/c mice were randomly assigned to the following groups for 9 weeks: Control, CDDP (3 mg/kg/week), CDDP+Q (quercetin 200 mg/kg/day administrated by gavage), CDDP+LL (a diet containing 0.8% leucine), CDDP+Q+LL, CDDP+HL (a diet containing 1.6% leucine), and CDDP+Q+HL. The results showed that quercetin in combination with LL or HL synergistically or additively attenuated CDDP-induced decreases in maximum grip strength, fat and muscle mass, muscle fiber size and MyHC level in muscle tissues. However, the combined effects on locomotor activity were less than additive. The combined treatments decreased the activation of the Akt/FoxO1/atrogin-1/MuRF1 signaling pathway (associated with muscle protein degradation), increased the activation of the mTOR and E2F-1 signaling pathways (associated with muscle protein synthesis and cell cycle/growth, respectively). The combined effects on signaling molecules present in muscle tissues were only additive or less. In addition, only Q+HL significantly increased glycogen levels compared to the CDDP group, while the combined treatments considerably decreased CDDP-induced proinflammatory cytokine and MCP-1 levels in the triceps muscle. Using tumor-bearing mice, we demonstrated that the combined treatments did not decrease the anticancer effect of CDDP. In conclusion, this study suggests that the combination of quercetin and leucine enhanced the suppressed effects on CDDP-induced muscle weakness and CRF through downregulating muscle atrophy and upregulating the glycogen level in muscle tissues without compromising the anticancer effect of CDDP. Multiple mechanisms, including regulation of several signaling pathways and decrease in proinflammatory mediator levels in muscles may contributed to the enhanced protective effect of the combined treatments on muscle atrophy.

Topics: Animals; Cisplatin; Fatigue; Glycogen; Leucine; Male; Mice; Muscular Atrophy; Quercetin

Critical illness myopathy (CIM) is a debilitating condition characterized by the preferential loss of the motor protein myosin. CIM is a by-product of critical care, attributed to impaired recovery, long-term complications, and mortality. CIM pathophysiology is complex, heterogeneous and remains incompletely understood; however, loss of mechanical stimuli contributes to critical illness-associated muscle atrophy and weakness. Passive mechanical loading and electrical stimulation (ES) therapies augment muscle mass and function. While having beneficial outcomes, the mechanistic underpinning of these therapies is less known. Therefore, here we aimed to assess the mechanism by which chronic supramaximal ES ameliorates CIM in a unique experimental rat model of critical care.. Rats were subjected to 8 days of critical care conditions entailing deep sedation, controlled mechanical ventilation, and immobilization with and without direct soleus ES. Muscle size and function were assessed at the single cell level. RNAseq and western blotting were employed to understand the mechanisms driving ES muscle outcomes in CIM.. Following 8 days of controlled mechanical ventilation and immobilization, soleus muscle mass, myosin : actin ratio, and single muscle fibre maximum force normalized to cross-sectional area (CSA; specific force) were reduced by 40-50% (P < 0.0001). ES significantly reduced the loss of soleus muscle fibre CSA and myosin : actin ratio by approximately 30% (P < 0.05) yet failed to effect specific force. RNAseq pathway analysis revealed downregulation of insulin signalling in the soleus muscle following critical care, and GLUT4 trafficking was reduced by 55% leading to an 85% reduction of muscle glycogen content (P < 0.01). ES promoted phosphofructokinase and insulin signalling pathways to control levels (P < 0.05), consistent with the maintenance of GLUT4 translocation and glycogen levels. AMPK, but not AKT, signalling pathway was stimulated following ES, where the downstream target TBC1D4 increased 3 logFC (P = 0.029) and AMPK-specific P-TBC1D4 levels were increased approximately two-fold (P = 0.06). Reduction of muscle protein degradation rather than increased synthesis promoted soleus CSA, as ES reduced E3 ubiquitin proteins, Atrogin-1 (P = 0.006) and MuRF1 (P = 0.08) by approximately 50%, downstream of AMPK-FoxO3.. ES maintained GLUT4 translocation through increased AMPK-TBC1D4 signalling leading to improved muscle glucose homeostasis. Soleus CSA and myosin content was promoted through reduced protein degradation via AMPK-FoxO3 E3 ligases, Atrogin-1 and MuRF1. These results demonstrate chronic supramaximal ES reduces critical care associated muscle wasting, preserved glucose signalling, and reduced muscle protein degradation in CIM.

Topics: Actins; AMP-Activated Protein Kinases; Animals; Critical Illness; Electric Stimulation Therapy; Glucose; Glucose Transporter Type 4; Glycogen; Insulin; Muscle, Skeletal; Muscular Atrophy; Muscular Diseases; Myosins; Rats

Obesity causes progressive lipid accumulation and insulin resistance within muscle cells and affects skeletal muscle fibres and muscle mass that demonstrates atrophy and dysfunction. This study investigated the effects of naringin on the metabolic processes of skeletal muscle in obese rats. Male Sprague Dawley rats were divided into five groups: the control group with normal diet and the obese groups, which were induced with a high-fat diet (HFD) for the first 4 weeks and then treated with 40 mg/kg of simvastatin and 50 and 100 mg/kg of naringin from week 4 to 8. The naringin-treated group showed reduced body weight, biochemical parameters, and the mRNA expressions of protein degradation. Moreover, increased levels of antioxidant enzymes, glycogen, glucose uptake, the expression of the insulin receptor substrate 1 (IRS-1), the glucose transporter type 4 (GLUT4), and the mRNA expressions of protein synthesis led to improved muscle mass in the naringin-treated groups. The in vitro part showed the inhibitory effects of naringin on digestive enzymes related to lipid and glucose homeostasis. This study demonstrates the potential benefits of naringin as a supplement for treating muscle abnormalities in obese rats by modulating the antioxidative status, regulating protein metabolism, and improved insulin resistance in skeletal muscle of HFD-induced insulin resistance in obese rats.

Topics: Animals; Antioxidants; Diet, High-Fat; Flavanones; Glucose; Glucose Transporter Type 4; Glycogen; Insulin; Insulin Receptor Substrate Proteins; Insulin Resistance; Male; Muscle, Skeletal; Muscular Atrophy; Obesity; Rats; Rats, Sprague-Dawley; RNA, Messenger; Simvastatin

Perturbations in skeletal muscle metabolism have been reported for a variety of neuromuscular diseases. However, the role of metabolism after constriction injury to a nerve and the associated muscle atrophy is unclear. We have analyzed rat tibialis anterior (TA) four weeks after unilateral constriction injury to the sciatic nerve (DMG) and in the contralateral control leg (CTRL) (n = 7) to investigate changes of the metabolome, immunohistochemistry and protein levels. Untargeted metabolomics identified 79 polar metabolites, 27 of which were significantly altered in DMG compared to CTRL. Glucose concentrations were increased 2.6-fold in DMG, while glucose 6-phosphate (G6-P) was unchanged. Intermediates of the polyol pathway were increased in DMG, particularly fructose (1.7-fold). GLUT4 localization was scattered as opposed to clearly at the sarcolemma. Despite the altered localization, we found GLUT4 protein levels to be increased 7.8-fold while GLUT1 was decreased 1.7-fold in nerve damaged TA. PFK1 and GS levels were both decreased 2.1-fold, indicating an inability of glycolysis and glycogen synthesis to process glucose at sufficient rates. In conclusion, chronic nerve constriction causes increased GLUT4 levels in conjunction with decreased glycolytic activity and glycogen storage in skeletal muscle, resulting in accumulation of intramuscular glucose and polyol pathway intermediates.

Topics: Animals; Disease Models, Animal; Glucose; Glucose Transporter Type 1; Glucose Transporter Type 4; Glycogen; Glycolysis; Humans; Male; Metabolomics; Muscle, Skeletal; Muscular Atrophy; Peripheral Nerve Injuries; Polymers; Rats; Sciatic Nerve

Topics: Animals; Cardiomegaly; Crosses, Genetic; Enzyme-Linked Immunosorbent Assay; Fever; Gene Expression Profiling; Glycogen; Heart Rate; Hypothyroidism; Lipolysis; Liver; Male; Mental Retardation, X-Linked; Mice; Mice, Inbred C57BL; Mice, Knockout; Monocarboxylic Acid Transporters; Muscle Hypotonia; Muscular Atrophy; Phenotype; Telemetry; Thermogenesis; Thermography; Thyroid Hormones; Time Factors; Triiodothyronine

Muscle wasting prevails in numerous diseases (e.g. diabetes, cardiovascular and kidney diseases, COPD,…) and increases healthcare costs. A major clinical issue is to devise new strategies preventing muscle wasting. We hypothesized that 8-week docosahexaenoic acid (DHA) supplementation prior to fasting may preserve muscle mass. Six-week-old C57BL/6 mice were fed a DHA-enriched or a control diet for 8 weeks and then fasted for 48 h.. Feeding mice a DHA-enriched diet prior to fasting elevated muscle glycogen contents, reduced muscle wasting, blocked the 55% decrease in Akt phosphorylation, and reduced by 30-40% the activation of AMPK, ubiquitination, or autophagy. The DHA-enriched diet fully abolished the fasting induced-messenger RNA (mRNA) over-expression of the endocannabinoid receptor-1. Finally, DHA prevented or modulated the fasting-dependent increase in muscle mRNA levels for Rab18, PLD1, and perilipins, which determine the formation and fate of lipid droplets, in parallel with muscle sparing.. These data suggest that 8-week DHA supplementation increased energy stores that can be efficiently mobilized, and thus preserved muscle mass in response to fasting through the regulation of Akt- and AMPK-dependent signalling pathways for reducing proteolysis activation. Whether a nutritional strategy aiming at increasing energy status may shorten recovery periods in clinical settings remains to be tested.

Topics: Adenosine Triphosphate; Animals; Dietary Supplements; Disease Models, Animal; Docosahexaenoic Acids; Endocannabinoids; Fasting; Fatty Acids; Gene Expression Regulation; Glycogen; Lipid Droplets; Lipid Metabolism; Mice; Mitogen-Activated Protein Kinases; Muscular Atrophy; Organ Size; Proteasome Endopeptidase Complex; Proteolysis; Proto-Oncogene Proteins c-akt; Signal Transduction; Ubiquitin; Ubiquitination

Pompe disease is due to a deficiency in acid-α-glucosidase (GAA) and results in debilitating skeletal muscle wasting, characterized by the accumulation of glycogen and autophagic vesicles. Given the role of lysosomes as a platform for mTORC1 activation, we examined mTORC1 activity in models of Pompe disease. GAA-knockdown C2C12 myoblasts and GAA-deficient human skin fibroblasts of infantile Pompe patients were found to have decreased mTORC1 activation. Treatment with the cell-permeable leucine analog L-leucyl-L-leucine methyl ester restored mTORC1 activation. In vivo, Pompe mice also displayed reduced basal and leucine-stimulated mTORC1 activation in skeletal muscle, whereas treatment with a combination of insulin and leucine normalized mTORC1 activation. Chronic leucine feeding restored basal and leucine-stimulated mTORC1 activation, while partially protecting Pompe mice from developing kyphosis and the decline in muscle mass. Leucine-treated Pompe mice showed increased spontaneous activity and running capacity, with reduced muscle protein breakdown and glycogen accumulation. Together, these data demonstrate that GAA deficiency results in reduced mTORC1 activation that is partly responsible for the skeletal muscle wasting phenotype. Moreover, mTORC1 stimulation by dietary leucine supplementation prevented some of the detrimental skeletal muscle dysfunction that occurs in the Pompe disease mouse model.

Topics: alpha-Glucosidases; Animals; Cell Line; Dietary Supplements; Dipeptides; Disease Models, Animal; Dose-Response Relationship, Drug; Fibroblasts; Glycogen; Glycogen Storage Disease Type II; Humans; Insulin; Kyphosis; Lysosomes; Mechanistic Target of Rapamycin Complex 1; Mice, Inbred C57BL; Mice, Knockout; Motor Activity; Multiprotein Complexes; Muscle, Skeletal; Muscular Atrophy; Myoblasts; RNA Interference; TOR Serine-Threonine Kinases; Transfection

Loss of muscle mass related to anti-cancer therapy is a major concern in cancer patients, being associated with important clinical endpoints including survival, treatment toxicity and patient-related outcomes. We investigated effects of voluntary exercise during cisplatin treatment on body weight, food intake as well as muscle mass, strength and signalling. Mice were treated weekly with 4 mg/kg cisplatin or saline for 6 weeks, and randomized to voluntary wheel running or not. Cisplatin treatment induced loss of body weight (29.8%, P < 0.001), lean body mass (20.6%, P = 0.001), as well as anorexia, impaired muscle strength (22.5% decrease, P < 0.001) and decreased glucose tolerance. In addition, cisplatin impaired Akt-signalling, induced genes related to protein degradation and inflammation, and reduced muscle glycogen content. Voluntary wheel running during treatment attenuated body weight loss by 50% (P < 0.001), maintained lean body mass (P < 0.001) and muscle strength (P < 0.001), reversed anorexia and impairments in Akt and protein degradation signalling. Cisplatin-induced muscular inflammation was not prevented by voluntary wheel running, nor was glucose tolerance improved. Exercise training may preserve muscle mass in cancer patients receiving cisplatin treatment, potentially improving physical capacity, quality of life and overall survival.

Topics: Animals; Anorexia; Body Weight; Cisplatin; Female; Gene Expression; Glucose Intolerance; Glycogen; Mice; Muscle Strength; Muscle, Skeletal; Muscular Atrophy; Physical Conditioning, Animal; Proto-Oncogene Proteins c-akt; Running; Signal Transduction

Poor skeletal muscle performance was shown to strongly predict mortality and long-term prognosis in a variety of diseases, including heart failure (HF). Despite the known benefits of aerobic exercise training (AET) in improving the skeletal muscle phenotype in HF, the optimal exercise intensity to elicit maximal outcomes is still under debate. Therefore, the aim of the present study was to compare the effects of high-intensity AET with those of a moderate-intensity protocol on skeletal muscle of infarcted rats. Wistar rats underwent myocardial infarction (MI) or sham surgery. MI groups were submitted either to an untrained (MI-UNT); moderate-intensity (MI-CMT, 60% Vo(2)(max)); or matched volume, high-intensity AET (MI-HIT, intervals at 85% Vo(2)(max)) protocol. High-intensity AET (HIT) was superior to moderate-intensity AET (CMT) in improving aerobic capacity, assessed by treadmill running tests. Cardiac contractile function, measured by echocardiography, was equally improved by both AET protocols. CMT and HIT prevented the MI-induced decay of skeletal muscle citrate synthase and hexokinase maximal activities, and increased glycogen content, without significant differences between protocols. Similar improvements in skeletal muscle redox balance and deactivation of the ubiquitin-proteasome system were also observed after CMT and HIT. Such intracellular findings were accompanied by prevented skeletal muscle atrophy in both MI-CMT and MI-HIT groups, whereas no major differences were observed between protocols. Taken together, our data suggest that despite superior effects of HIT in improving functional capacity, skeletal muscle adaptations were remarkably similar among protocols, leading to the conclusion that skeletal myopathy in infarcted rats was equally prevented by either moderate-intensity or high-intensity AET.

Topics: Animals; Citrate (si)-Synthase; Disease Models, Animal; Exercise Therapy; Exercise Tolerance; Glycogen; Hexokinase; Male; Muscle Contraction; Muscle, Skeletal; Muscular Atrophy; Myocardial Contraction; Myocardial Infarction; Myocardium; Oxidation-Reduction; Oxygen Consumption; Proteasome Endopeptidase Complex; Rats; Rats, Wistar; Ultrasonography

Onabotulinum toxin A (BTX-A) is a frequently used treatment modality to relax spastic muscles by preventing acetylcholine release at the motor nerve endings. Although considered safe, previous studies have shown that BTX-A injections cause muscle atrophy and deterioration in target and non-target muscles. Ideally, muscles should fully recover following BTX-A treatments, so that muscle strength and performance are not affected in the long-term. However, systematic, long-term data on the recovery of muscles exposed to BTX-A treatments are not available, thus practice guidelines on the frequency and duration of BTX-A injections, and associated recovery protocols, are based on clinical experience with little evidence-based information. Therefore, the purpose of this study was to investigate muscle recovery following a six months, monthly BTX-A injection (3.5 U/kg) protocol. Twenty seven skeletally mature NZW rabbits were divided into 5 groups: Control (n=5), zero month recovery - BTX-A+0M (n=5), one month recovery - BTX-A+1M (n=5), three months recovery - BTX-A+3M (n=5), and six months recovery - BTX-A+6M (n=7). Knee extensor strength, muscle mass and percent contractile material in injected and contralateral non-injected muscles was measured at each point of recovery. Strength and muscle mass were partially and completely recovered in injected and contralateral non-injected muscles for BTX-A+6M group animals, respectively. The percent of contractile material partially recovered in the injected, but did not recover in the contralateral non-injected muscles. We conclude from these results that neither target nor non-target muscles fully recover within six months of a BTX-A treatment protocol and that clinical studies on muscle recovery should be pursued.

Topics: Animals; Botulinum Toxins, Type A; Female; Femoral Nerve; Glycogen; Injections, Intramuscular; Muscle Weakness; Muscular Atrophy; Quadriceps Muscle; Rabbits

This study investigated whether exercise training could prevent the negative side effects of dexamethasone. Rats underwent a training period and were either submitted to a running protocol (60% physical capacity, 5 days/week for 8 weeks) or kept sedentary. After this training period, the animals underwent dexamethasone treatment (1 mg/kg per day, i.p., 10 days). Glycemia, insulinemia, muscular weight and muscular glycogen were measured from blood and skeletal muscle. Vascular endothelial growth factor (VEGF) protein was analyzed in skeletal muscles. Dexamethasone treatment evoked body weight loss (-24%), followed by muscular atrophy in the tibialis anterior (-25%) and the extensor digitorum longus (EDL, -15%). Dexamethasone also increased serum insulin levels by 5.7-fold and glucose levels by 2.5-fold compared to control. The exercise protocol prevented atrophy of the EDL and insulin resistance. Also, dexamethasone-treated rats showed decreased muscular glycogen (-41%), which was further attenuated by the exercise protocol. The VEGF protein expression decreased in the skeletal muscles of dexamethasone-treated rats and was unaltered by the exercise protocol. These data suggest that exercise attenuates hyperglycemia and may also prevent insulin resistance, muscular glycogen loss and muscular atrophy, thus suggesting that exercise may have some benefits during glucocorticoid treatment.

Topics: Animals; Blood Glucose; Body Weight; Dexamethasone; Exercise Test; Glucocorticoids; Glycogen; Hyperinsulinism; Insulin; Insulin Resistance; Male; Muscle, Skeletal; Muscular Atrophy; Physical Conditioning, Animal; Rats; Rats, Wistar; Time Factors

It was reported that Dipsaci radix (DR) has a reinforcement effect on the bone-muscle dysfunction in the oriental medical classics and the experimental animal studies. The muscle atrophy was induced by unilateral transection of the sciatic nerve of the rats. Water-extract of DR was used as treatment once a day for 12 days. The muscle weights of the hind limb, atrophic changes, glycogen contents, compositions and cross-section areas of muscle fiber types in soleus and medial gastrocnemius were investigated. Muscle fiber type was classified to type-I and type-II with MHCf immunohistochemistry. Furthermore, Bax and Bcl-2 expressions were observed with immunohistochemiatry. DR treatment significantly increased muscle weights of soleus, medial gastrocnemius, lateral gastrocnemius, and posterior tibialis of the damaged hind limb. DR treatment reduced apoptotic muscle nuclei and hyaline-degenerated muscle fibers in soleus and medial gastrocnemius of the damaged hind limb. DR treatment also significantly increased glycogen contents in medial gastrocnemius of the damaged hind limb. DR treatment significantly attenuated the slow-to-fast shift in soleus of the damaged hind limb but not in medial gastrocnemius. DR treatment significantly increased cross-section areas of type-I and type-II fibers in soleus and medial gastrocnemius of the damaged hind limb. In soleus and medial gastrocnemius, DR treatment significantly reduced Bax positive muscle nuclei in the damaged hind limb. These results suggest that DR treatment has an anti-atrophic effect and an anti-apoptotic effect against myonuclear apoptosis induced by the peripheral nerve damage.

Topics: Animals; Apoptosis; bcl-2-Associated X Protein; Cell Nucleus; Dipsacaceae; Glycogen; Hindlimb; Hyalin; Male; Muscle Fibers, Skeletal; Muscle, Skeletal; Muscular Atrophy; Organ Size; Plant Extracts; Plant Roots; Protective Agents; Rats; Rats, Sprague-Dawley; Sciatic Nerve

The aim of the present study was to evaluate the effect of joint immobilization on morphometric parameters and glycogen content of soleus muscle treated with clenbuterol. Male Wistar (3-4 months old) rats were divided into 4 groups (N = 6 for each group): control, clenbuterol, immobilized, and immobilized treated with clenbuterol. Immobilization was performed with acrylic resin orthoses and 10 microg/kg body weight clenbuterol was administered subcutaneously for 7 days. The following parameters were measured the next day on soleus muscle: weight, glycogen content, cross-sectional area, and connective tissue content. The clenbuterol group showed an increase in glycogen (81.6%, 0.38 +/- 0.09 vs 0.69 +/- 0.06 mg/100 g; P < 0.05) without alteration in weight, cross-sectional area or connective tissue compared with the control group. The immobilized group showed a reduction in muscle weight (34.2%, 123.5 +/- 5.3 vs 81.3 +/- 4.6 mg; P < 0.05), glycogen content (31.6%, 0.38 +/- 0.09 vs 0.26 +/- 0.05 mg/100 mg; P < 0.05) and cross-sectional area (44.1%, 2574.9 +/- 560.2 vs 1438.1 +/- 352.2 microm(2); P < 0.05) and an increase in connective tissue (216.5%, 8.82 +/- 3.55 vs 27.92 +/- 5.36%; P < 0.05). However, the immobilized + clenbuterol group showed an increase in weight (15.9%; 81.3 +/- 4.6 vs 94.2 +/- 4.3 mg; P < 0.05), glycogen content (92.3%, 0.26 +/- 0.05 vs 0.50 +/- 0.17 mg/100 mg; P < 0.05), and cross-sectional area (19.9%, 1438.1 +/- 352.2 vs 1724.8 +/- 365.5 microm(2); P < 0.05) and a reduction in connective tissue (52.2%, 27.92 +/- 5.36 vs 13.34 +/- 6.86%; P < 0.05). Statistical analysis was performed using Kolmogorov-Smirnov and homoscedasticity tests. For the muscle weight and muscle glycogen content, two-way ANOVA and the Tukey test were used. For the cross-sectional area and connective tissue content, Kruskal-Wallis and Tukey tests were used. This study emphasizes the importance of anabolic pharmacological protection during immobilization to minimize skeletal muscle alterations resulting from disuse.

Topics: Adrenergic beta-Agonists; Animals; Clenbuterol; Connective Tissue; Glycogen; Immobilization; Male; Muscle Fibers, Skeletal; Muscle, Skeletal; Muscular Atrophy; Organ Size; Rats; Rats, Wistar; Time Factors

Age-related skeletal muscle sarcopenia has been extensively studied and smooth muscle sarcopenia has been recently described, but age-related cardiac sarcopenia has not been previously examined. Therefore, we evaluated adult (7.5+/-0.5 months; n = 27) and senescent (31.8+/-0.4 months; n = 26) C57BL/6J mice for cardiac sarcopenia using physiological, histological, and biochemical assessments. Mice do not develop hypertension, even into senescence, which allowed us to decouple vascular effects and monitor cardiac-dependent variables. We then developed a mathematical model to describe the relationship between age-related changes in cardiac muscle structure and function. Our results showed that, compared to adult mice, senescent mice demonstrated increased left ventricular (LV) end diastolic dimension, decreased wall thickness, and decreased ejection fraction, indicating dilation and reduced contractile performance. Myocyte numbers decreased, and interstitial fibrosis was punctated but doubled in the senescent mice, indicating reparative fibrosis. Electrocardiogram analysis showed that PR interval and QRS interval increased and R amplitude decreased in the senescent mice, indicating prolonged conduction times consistent with increased fibrosis. Intracellular lipid accumulation was accompanied by a decrease in glycogen stores in the senescent mice. Mathematical simulation indicated that changes in LV dimension, collagen deposition, wall stress, and wall stiffness precede LV dysfunction. We conclude that age-related cardiac sarcopenia occurs in mice and that LV remodeling due to increased end diastolic pressure could be an underlying mechanism for age-related LV dysfunction.

Topics: Aging; Animals; Collagen; Electrocardiography; Female; Fibrosis; Glycogen; Heart; Lipid Metabolism; Male; Mice; Mice, Inbred C57BL; Models, Biological; Muscular Atrophy; Myocardial Contraction; Myocardium; Myocytes, Cardiac; Ventricular Function, Left

Topics: Adult; Creatine Kinase; Diagnosis, Differential; Electromyography; Glycogen; Glycogen Storage Disease Type II; Humans; Lysosomes; Male; Muscle Weakness; Muscular Atrophy; Respiratory Insufficiency; Respiratory Muscles; Respiratory Paralysis; Thorax; Tomography, X-Ray Computed

The aim of this study was to use the glycogen depletion technique to determine whether reinnervated muscle fibers could be distinguished from denervated muscle fibers by their size or by neural cell adhesion molecule (NCAM) expression.. Medial gastrocnemius muscles of five adult Fischer rats were reinnervated from embryonic neurons transplanted into the distal stump of the tibial nerve. Ten weeks later, the transplants were stimulated repeatedly to deplete reinnervated muscle fibers of glycogen. Areas of reinnervated (glycogen-depleted) muscle fibers were measured and assessed for NCAM expression. The areas of muscle fibers from reinnervated, denervated (n=5) and unoperated control muscles (n=5) were compared.. Mean reinnervated muscle fiber area was significantly larger than the mean for denervated fibers (mean +/- SE: 40 +/- 6 and 10 +/- 1% of unoperated control fibers, respectively). NCAM was expressed in 55 +/- 7% of reinnervated fibers (mean +/- SE; range: 42-77%). The mean areas of reinnervated fibers that did or did not express NCAM were similar. NCAM was only expressed in some fibers in completely denervated muscles.. Our data show that NCAM expression does not differentiate muscle denervation or reinnervation. Quantifying the area of large fibers did distinguish reinnervated muscle fibers from denervated fibers and showed that reinnervation of muscle from neurons placed in peripheral nerve is a strategy to rescue muscle from atrophy.

Topics: Analysis of Variance; Animals; Cell Transplantation; Electromyography; Embryo, Mammalian; Female; Glycogen; Muscle Denervation; Muscle Fibers, Skeletal; Muscular Atrophy; Nerve Regeneration; Neural Cell Adhesion Molecules; Neurons; Rats; Rats, Inbred F344; Spinal Cord; Tibial Nerve

Muscle biopsies from chronic steroid (glucocorticoid) myopathy, non-steroid histochemical type-2 fiber atrophy, and muscle denervation patients were studied to determine if their glycogen contents, or enzymes involved in glycogenolysis and glycolysis might be related to their fiber atrophy.. Fast frozen muscle biopsies from the above patients and from patients later judged by histochemistry to be normal were assayed enzymatically for glycogen content, for enzymes involved in glycogenolysis, and for 6 of the enzymes involved in glycolysis.. All three groups of patients had glycogen content, but only the chronic steroid myopathy muscle had statistically less glycogen content than did normal human muscle. All 3 groups had statistically low mean values compared to normal muscles for glycogen phosphorylase activity. This suggests that the biosynthesis and phosphorolysis of glycogen are not involved in muscle fiber atrophy, and glucocorticoid administration does not activate muscle glycogen biosynthesis. Histochemical type-2 fiber atrophy muscles were low compared to normal muscles in three glycogenolysis enzyme activities plus four glycolysis enzyme activities. Muscles from denervation patients were low compared to normal muscles in three glycogenolysis enzyme activities plus five glycolysis enzyme activities. This suggests that muscle denervation may lower the rate of glycolysis enough to fail to provide sufficient pyruvate for mitochondrial ATP biosynthesis, resulting in insufficient protein biosynthesis in both fiber types.

Topics: Adult; Aged; Female; Glycogen; Glycogenolysis; Glycolysis; Humans; Male; Middle Aged; Muscle Denervation; Muscle, Skeletal; Muscular Atrophy; Muscular Diseases

Severe muscle atrophy occurs after complete denervation. Here, Embryonic Day 14-15 ventral spinal cord cells were transplanted into the distal tibial nerve stump of adult female Fischer rats to provide a source of neurons for muscle reinnervation. Our aim was to characterize the properties of the reinnervated motor units and muscle fibers. Some reinnervated motor units contracted spontaneously. Electrical stimulation of the transplants at increasing intensity produced an average (+/- SE) of 7 +/- 1 electromyographic and force steps. Each signal increment represented the excitation of another motor unit. These reinnervated units exerted an average force of 12.0 +/- 1.5 mN, strength similar to that of control fatigue-resistant units. Repeated transplant stimulation depleted 17% of the muscle fibers of glycogen, an indication of some functional reinnervation. Reinnervated (glycogen-depleted), denervated (no cells transplanted), and control fibers were of histochemical type I, IIA, or IIB. Fibers of the same type were grouped after reinnervation. The proportion of fiber types also changed. Reinnervated fibers were primarily type IIA, whereas most fibers in denervated and control muscles were type IIB. Reinnervated fibers of each type had significantly larger cross-sectional areas than the corresponding fiber types in denervated muscles. These data suggest that neurons with different properties can reside in the unusual environment of the adult rat peripheral nerve, make functional connections with muscle, specify muscle fiber type, and reduce the amount that each type atrophies.

Topics: Animals; Anterior Horn Cells; Cell Size; Electric Stimulation; Electromyography; Female; Glycogen; Muscle Contraction; Muscle Denervation; Muscle Fibers, Skeletal; Muscle, Skeletal; Muscular Atrophy; Nerve Regeneration; Rats; Rats, Inbred F344; Spinal Cord; Stress, Mechanical

The present study was undertaken to identify the metabolic and contractile characteristics of fast- and slow-twitch skeletal muscles in a transgenic mouse model of amyotrophic lateral sclerosis (ALS). In addition, we investigated the effects of oral creatine supplementation on muscle functional capacity in this model. Transgenic mice expressing a mutant (G93A) or wild type human SOD1 gene (WT) were supplemented with 2% creatine monohydrate from 60 to 120 days of age. Body weight, rotorod performance and grip strength were evaluated. In vitro contractility was evaluated on isolated m. soleus and m. extensor digitorum longus (EDL), and muscle metabolites were determined. Body weight, rotorod performance and grip strength were markedly decreased in G93A compared to WT mice, but were unaffected by creatine supplementation. Muscle ATP content decreased and glycogen content increased in G93A versus WT in both muscle types, but were unaffected by creatine supplementation. Muscle creatine content increased following creatine intake in G93A soleus. Twitch and tetanic contractions showed markedly slower contraction and relaxation times in G93A versus WT in both muscle types, with no positive effect of creatine supplementation. EDL but not soleus of G93A mice showed significant atrophy, which was partly abolished by creatine supplementation. It is concluded that overexpression of a mutant SOD1 transgene has profound effects on metabolic and contractile properties of both fast- and slow-twitch skeletal muscles. Furthermore, creatine intake does not exert a beneficial effect on muscle function in a transgenic mouse model of ALS.

Topics: Adenosine Triphosphate; Amyotrophic Lateral Sclerosis; Animals; Body Weight; Creatine; Glycogen; Humans; Mice; Mice, Transgenic; Models, Animal; Motor Activity; Muscle Contraction; Muscle Fibers, Fast-Twitch; Muscle Fibers, Slow-Twitch; Muscle, Skeletal; Muscular Atrophy; Mutation; Superoxide Dismutase; Superoxide Dismutase-1

Clinical and morphological features have been studied in 11 late onset Acid Maltase Deficient (AMD) patients. All patients have been diagnosed on biochemical evidence of acid maltase deficiency on muscle biopsy. Molecular studies showed a heterozygous mutation (IVS1-13 T > G transversion resulting in aberrant splicing) in the GSDII gene, which is the most common mutation in late onset AMD patients. Morphological features in muscle biopsy showed a vacuolar myopathy and Golgi apparatus proliferation within fibres. The peripheral areas of autophagic vacuoles were positive for caveolin-3 and dystrophin, documenting an extensive membrane turnover. The ultrastructural study of muscle biopsy showed randomly distributed or isolated vesicles sometimes derived from the Golgi apparatus. In subsarcolemmal region, lipofucsin bodies and abnormal mitochondria with crystalline inclusions were observed. Primary and secondary lysosomes were typically filled with glycogen. These data suggest a predominant role of Golgi in vesicle proliferation and extensive intra-fibral membrane remodelling. The pathological changes observed are selective for muscle fibres (mostly in type 1) and for muscle groups (mainly proximal). An attractive hypothesis for the variability of clinical phenotype in adult and infantile onset AMD patients is that in the former, an aberrant transcript of smaller size may have originated from alternative splicing (exon 2 skipping). A residual enzyme activity is detectable in muscle, but the intracellular processing of the enzyme precursor from Golgi to the mature form in lysosomes might be blocked.

Topics: Acid Phosphatase; Adult; Age of Onset; Aged; Alternative Splicing; Biomarkers; Female; Genetic Predisposition to Disease; Glucan 1,4-alpha-Glucosidase; Glycogen; Golgi Apparatus; Heterozygote; Humans; Immunohistochemistry; Lysosomes; Male; Microscopy, Electron; Middle Aged; Mitochondria, Muscle; Muscle Fibers, Skeletal; Muscle, Skeletal; Muscular Atrophy; Mutation; Sarcolemma; Time Factors; Vacuoles

Topics: Abnormalities, Multiple; Adolescent; Biopsy; Chromosome Deletion; Chromosomes, Human, Pair 22; Craniofacial Abnormalities; Creatine Kinase; Glycogen; Humans; Male; Microscopy, Electron; Muscle, Skeletal; Muscular Atrophy; Neuromuscular Diseases

Reduction of physical activity due to disease or environmental restraints, such as total bed rest or exposure to spaceflight, leads to atrophy of skeletal muscle and is frequently accompanied by alterations in food intake and the concentration of metabolic regulatory hormones such as insulin. Hindlimb suspension of laboratory rats, as a model for microgravity, also shows marked atrophy of gravity dependent muscles along with a reduced gain in body weight. Suspended rats exhibit enhanced sensitivity to insulin-induced glucose uptake when compared with normal control rats and resistance to insulin action when compared with control rats matched similarly for reduced body weight gain. These changes are accompanied by decreased insulin binding and tyrosine kinase activity in soleus but not plantaris muscle, unchanged glucose uptake by perfused hindlimb and decreased sensitivity but not responsiveness to insulin-induced suppression of net proteolysis in hindlimb skeletal muscle. These findings suggest that loss of insulin sensitivity during muscle atrophy is associated with decreased insulin binding and tyrosine kinase activity in atrophied soleus muscle along with decreased sensitivity to the effects of insulin on suppressing net protein breakdown but not on enhancing glucose uptake by perfused hindlimb.

Topics: Animals; Body Weight; Glucose; Glycogen; Hindlimb; Immobilization; Insulin; Insulin Resistance; Liver; Liver Glycogen; Male; Muscle, Skeletal; Muscular Atrophy; Protein-Tyrosine Kinases; Rats; Rats, Sprague-Dawley; Receptor, Insulin; Weightlessness Simulation

1. Biopsies of the extensor hallucis longus (EHL) and gastrocnemius (G) muscles of four captive black bears (Ursus americanus) were obtained prior to denning (PRE), during denning (DEN) and following the Spring arousal (POST). 2. Glycogen, triglyceride and protein concentrations did not differ significantly between the three groups. Likewise, the activity of citrate synthase, a mitochondrial oxidative enzyme, was not significantly different between the three groups. 3. DNA concentrations in DEN samples increased 30% compared to other groups while RNA concentrations were significantly elevated in POST samples. The RNA/DNA ratios were significantly depressed during DEN. 4. These results suggest a degree of muscle atrophy during DEN, with the potential for an increased capacity for muscle protein synthesis following the Spring arousal.

Topics: Adaptation, Physiological; Animals; Citrate (si)-Synthase; DNA; Female; Glycogen; Male; Muscles; Muscular Atrophy; Proteins; RNA; Triglycerides; Ursidae

Electrical stimulation to augment or maintain muscle performance has been well documented. The purpose of this preliminary report is to present the results of a single-case study conducted to determine the order of activation of skeletal muscle fibers as a result of electrical stimulation. The subject's quadriceps femoris muscles were electrically stimulated at 80% of maximal isometric torque. Pre-stimulation and immediate post-stimulation muscle biopsy samples were obtained, and a modification of the glucogen-depletion method was used to determine activation of muscle fibers. The pre-stimulation muscle biopsy sample demonstrated uniform periodic acid-Schiff (PAS)-positive staining in all fiber types, whereas the post-stimulation muscle biopsy sample showed glycogen depletion of type II muscle fibers. The most PAS-negative muscle fibers were type IIa skeletal muscle fibers. The results of this single-case study provide evidence that electrical stimulation, as described, selectively activates type II skeletal muscle fibers. The implication of this finding is that, in many chronic diseases, type II fibers are selectively and preferentially affected. Electrical stimulation may be a clinically viable technique to use in patients with type II fiber involvement.

Topics: Adult; Biopsy; Electric Stimulation Therapy; Evaluation Studies as Topic; Glycogen; Humans; Male; Muscle Contraction; Muscles; Muscular Atrophy; Periodic Acid-Schiff Reaction

Results of hindlimb suspension and space flight experiments with rats examine the effects of weightlessness simulation, weightlessness, and delay in postflight recovery of animals. Parameters examined were body mass, protein balance, amino acid metabolism, glucose and glycogen metabolism, and hormone levels. Tables show metabolic responses to unweighting of the soleus muscle.

Topics: Ammonium Chloride; Animals; Body Weight; Corticosterone; Female; Glucose; Glycogen; Hindlimb Suspension; Insulin; Muscle Proteins; Muscle, Skeletal; Muscular Atrophy; Rats; Rats, Sprague-Dawley; Space Flight; Weightlessness; Weightlessness Simulation

Topics: Adolescent; Biopsy; Glycogen; Humans; Male; Microscopy, Electron; Muscles; Muscular Atrophy; Rhabdomyolysis; Sports; Weight Lifting

Comparison of hindlimb muscles of rats flown on Spacelab-3 or tail-traction-suspended showed that 11-17 h reloading post-flight might have altered the results. Soleus atrophied, plantaris, gastrocnemius and extensor digitorum longus grew slower, and tibialis anterior grew normally. In both flight and simulated soleus and plantaris, higher tyrosine and greater glutamine/glutamate ratio indicated negative protein balance and increased glutamine production, respectively, relative to controls. Aspartate was lower in these muscles. Reloading generally decreased tyrosine, but increased aspartate and glutamine/glutamate. These data showed that at 12 h of reloading after flight is characterized by reversal to varying extents of effects of unloading.

Topics: Adaptation, Physiological; Amino Acids, Dicarboxylic; Animals; Fumarates; Glycogen; Hindlimb Suspension; Male; Muscle Proteins; Muscle, Skeletal; Muscular Atrophy; Rats; Research Design; Space Flight; Tail; Tyrosine; Weightlessness; Weightlessness Simulation

Adult acid maltase deficiency (AMD, glycogen storage disease type II) may involve respiratory muscles leading to severe respiratory failure even before the affection of pelvic girdle muscles has turned the patient non-ambulatory. The case of a 29-year-old woman is presented to demonstrate that long-term survival is possible even after acute respiratory failure has occurred. The examination of the patient's family revealed the diagnosis of AMD in her 24-year-old sister, so far without clinical symptoms. The comparison between the two patients of serum enzyme elevations (CK, LDH, GOT, GPT, aldolase) suggested that both physical activity and the stage of the disease may be correlated with the degree of enzyme level elevation.

Topics: Adult; alpha-Glucosidases; Biopsy; Diagnosis, Differential; Electromyography; Female; Follow-Up Studies; Glucan 1,4-alpha-Glucosidase; Glycogen; Glycogen Storage Disease; Glycogen Storage Disease Type II; Humans; Muscles; Muscular Atrophy

Whole-body hypokinetic-hypodynamic (H/H) suspension, unlike other models of muscle disuse, allows voluntary contractile activity. This study examined the oxidative capacity and insulin sensitivity of rat hindlimb muscles subjected to 7 days of suspension H/H conditions. Oxidative capacity was determined by measuring citrate synthase activity and cytochrome c concentration in soleus and gastrocnemius muscles. A perfused hindquarter preparation was used to measure glucose uptake rates at rest with physiological and supramaximal concentrations of insulin in the perfusate. Citrate synthase activity was 17% lower in soleus and 23% lower in gastrocnemius muscles from H/H rats. Similarly, a 29% decrease in H/H rat gastrocnemius cytochrome c concentration was observed. Rates of glucose uptake were lower in muscles from H/H rats compared with controls at physiological levels of insulin and did not increase in response to a further increase in insulin concentration. Muscles undergoing a significant loss in mass after 7 days suspension were found to have increased glycogen concentrations. In conclusion, data presented in this study suggest that hindlimb muscle disuse, brought about by whole-body suspension, results in a decreased aerobic capacity in load bearing muscles and a lowered insulin sensitivity in perfused rat hindlimb muscles.

Topics: Animals; Cytochrome c Group; Glucose; Glycogen; Hindlimb; Insulin; Lactates; Male; Muscles; Muscular Atrophy; Organ Size; Oxygen Consumption; Rats; Rats, Inbred Strains

The clinical course of metabolic myopathies is dominated by progressive muscle weakness and wasting or aching contraction and recurrent rhabdomyolysis with intense exercise. Vacuolar muscle fibre degeneration is the leading pathological finding on routine histological examination. For further characterization of those histologically empty looking vacuoles, histochemistry and electron microscopy are employed. Increase of glycogen, lipid droplets or mitochondria can often be demonstrated and indicate the need for subsequent biochemical identification of the underlying metabolic defect. Some other metabolic myopathies that cause recurrent rhabdomyolysis lack myopathological abnormalities. These can only be diagnosed biochemically, but additional new histochemical screening methods might be helpful.

Topics: Biopsy; Contracture; Glycogen; Glycogen Storage Disease; Humans; Lipid Metabolism; Lipid Metabolism, Inborn Errors; Microscopy, Electron; Mitochondria, Muscle; Muscle Hypotonia; Muscles; Muscular Atrophy; Muscular Diseases; Rhabdomyolysis; Vacuoles

The effects of progressive resistance exercise (PRE) training for 4 weeks on the hypotrophic quadriceps muscle were investigated in 23 young healthy male soccer players, who had been immobilized in a plaster cast 4-6 weeks after knee ligament injuries. The subjects were allocated to two training regimes where the injured leg was trained for periods of varying duration, whereas the intensity and frequency of exercise were alike in the two groups. However no significant differences were detected between the two training groups. In the whole material the lean thigh volume of the injured leg increased from 4.09 to 4.47 litres (p less than 0.001), whereas the fat component of the thigh was unchanged. The dynamic strength (1 RM) of the injured leg increased from 14.0 kg to 27.0 kg and amounted to 87% of the control leg after 4 weeks of training. At this time the maximum isometric strength amounted to 114 Nm, which was 63% of strength in the control leg. Succinate dehydrogenase (SDH) in homogenates of muscle biopsy sample increased (i.e. 20%, p less than 0.05) to the same level as found in the control leg. No changes in phosphofructokinase (PFK) were observed. The type I fibre distribution was lower in the immobilized leg than in the control leg. These results indicate that, following muscular hypotrophy resulting from 4-6 weeks of immobilization, dynamic exercise can restore the oxidative potential, whereas the size and strength are only partly recovered.

Topics: Adolescent; Adult; Anthropometry; Exercise Therapy; Glycogen; Humans; Male; Muscles; Muscular Atrophy; Phosphofructokinase-1; Succinate Dehydrogenase; Thigh

The comparative electrophysiologic, histochemical, and biochemical investigation of the anterior tibial muscle of 13 alcoholics indicates that neuropathy could be the cause of the chronic muscle weakness and wasting. Myopathic alterations did not predominate in the findings. It was concluded that the proximal muscle atrophy could also be attributed to neurogenic damage. Histochemical reactions in muscle specimens showed a selective type 2 atrophy and a slight increase of the mean diameter of type 1 fibres. Biochemical investigations revealed that the activities of a number of enzymes representative of energy supplying pathways--the glycogenolysis and glycolysis--as well as acid phosphatase activity in the muscle were lowered. A relationship could be assumed between the lowered glycolytic activity and the decline of the mean diameter of type 2 fibres. Oxidative enzymes were of similar activity in the alcoholics and the control group. The glycolytic enzyme activities were particularly important, being the most sensitive indicators of the onset, intensity, and course of neurogenic damage. These activities probably normalise during reinnervation of a muscle earlier than do the morphologic alterations; however, they were markedly lower in alcoholics with impaired liver function and cachexia, probably because of the catabolic metabolic conditions present in these cases.

Topics: Adenosine Triphosphatases; Adult; Alcoholism; Axons; Dihydrolipoamide Dehydrogenase; Electromyography; Female; Glycogen; Glycolysis; Humans; Male; Middle Aged; Muscles; Muscular Atrophy; Neural Conduction; Reflex, Stretch; Sensation

This report describes a female patient with childhood form of acid maltase deficiency who survived till fifteen years old. Although acid alpha-1,4-glucosidase was deficient in the liver, kidney, skeletal and cardiac muscles, neutral alpha-1,4-glucosidase was present in normal concentrations in those organs. On light microscopic examination, numerous intracytoplasmic vacuoles containing acid phosphatase positive granules and PAS positive materials were present in both type 1 and 2 A fibers, predominantly in the latter. The striking finding in the present case was a selective type 2 fiber atrophy with type 2 B fiber deficiency believed to result from type 2 motor neuron dysfunction in the spinal cord. Electron microscopic study revealed extensive glycogen particle accumulation, autophagic vacuoles and myelin figures in the muscle fibers.

Topics: Adolescent; alpha-Glucosidases; Electromyography; Female; Glucan 1,4-alpha-Glucosidase; Glucosidases; Glycogen; Glycogen Storage Disease; Glycogen Storage Disease Type II; Humans; Muscles; Muscular Atrophy; Organoids; Vacuoles

A case of an adult polysaccharide myopathy is reported in a patient with progressive muscular atrophy and weakness of limb girdles. Histochemistry and electron microscopy showed in some muscle fibers, a storage material composed of amylopectin-like filaments. Biochemical results were normal and no enzyme deficiency was found. This case is compared with three other published cases. Pathological conditions with amylopectin or amylopectin-like storage material are reviewed.

Topics: Amylopectin; Glycogen; Humans; Male; Microscopy, Electron; Middle Aged; Muscles; Muscular Atrophy; Polysaccharides

1. The glycogen-depletion patterns were studies as a measure of muscle-fibre recruitment in patients after leg injuries (fractures, ligament injuries). Intermittent isometric and dynamic isokinetic knee extension were performed with 30 and 50% of the maximal isometric torque of the injured leg. In a third group isokinetic and dynamic exercise with weights were compared by using maximal effort procedures. 2. The 30% maximal voluntary contraction programme, which corresponded to 16% of maximal voluntary contraction of the non-injured leg, resulted in glycogen depletion of type I fibres, which was significant only in the isometric exercise. In the 50% maximal voluntary contraction programme (41% of maximal voluntary contraction of the non-injured leg) depletion of type II fibres dominated and was significant with isometric exercises. In the maximal effort programmes there was a significant depletion of type II fibres. 3. Subjects with a relatively large reduction in strength or a small number of type I fibres demonstrated more depletion of these fibres than other subjects. 4. In patients with moderately reduced muscle strength and muscle fibre atrophy static or dynamic exercises using at least 50% of the actual maximal voluntary contraction can thus be used to recruit and train type II fibres.

Topics: Adolescent; Adult; Exercise Therapy; Female; Glycogen; Humans; Isometric Contraction; Leg Injuries; Male; Middle Aged; Muscle Contraction; Muscles; Muscular Atrophy

Striated muscle from patients taking more than 80 g of alcohol each day shows selective atrophy of the type II fibres which are dependent on glycogenolytic pathways. This atrophy is associated with an excess of glycogen and lipid within the fibres and may represent a selective metabolic insult.

Topics: Adult; Aged; Alcoholism; Cytoplasmic Granules; Female; Glycogen; Humans; Lipids; Male; Microscopy, Electron; Middle Aged; Muscles; Muscular Atrophy

Topics: Animals; Dogs; Electromyography; Female; Glycogen; Male; Mitochondria, Muscle; Muscles; Muscular Atrophy; Prednisolone; Vacuoles

The effects of denervation on the gastrocnemius muscle of the frog were studied by histologic and histochemical methods. Thirteen Rana pipiens underwent unilateral sciatic neurotomy and were sacrificed weekly as long as 46 days. Of the three normal populations of muscle fibers, the small fibers underwent atrophy, the intermediate sized fibers remained unchanged in size, and the large fibers either did not change or underwent hypertrophy between 21 and 46 days. Necrosis of muscle fibers did not occur. Histochemical stains showed persistence of the normal pattern after denervation. The small fibers continued to have a high concentration of both oxidative and glycolytic enzyme activity (NADH-TR, SDH, phosphorylase), and the large fibers continued to have a low concentration of these enzymes. Depletion of glycogen stores was seen with PAS. Hypertrophic muscle fibers had mostly subsarcolemmal nuclei and few internal nuclei, suggesting that they may be physiologically tonic rather than twitch fibers. Achilles tenotomy at the time of denervation prevented the hypertrophy of large fibers. Abnormal inclusions have been demonstrated in mammalian muscle following tenotomy alone, but were not seen in the frog.

Topics: Achilles Tendon; Adenosine Triphosphatases; Animals; Anura; Glycogen; Hypertrophy; Muscle Denervation; Muscles; Muscular Atrophy; Rana pipiens; Time

Acid maltase deficiency is described in non-identical adult twins. The onset of the disease can be traced into late infancy; the clinical picture is one of severe muscular dystrophy; respiratory insuficiency was the cause of death in one case. The autopsy showed the central nervous system, heart and liver to be spared. Glycogen filled vacuoles are found in skin, mesenchymal cells, small nerves and skeletal muscles. The light microscopic study of 9 different muscles showed extremely variable involvement ranging from normal appearance to overt vacuolization. A 6--20% residual acid alpha-glucosidase activity was found in visceral organs, cultured fibroblasts and in some skeletal muscles. No satisfactory explanation can be given why this generalized acid alpha-glucosidase deficiency produces a selective involvement of skeletal muscles. If compared with infantile AMD (Pompe's disease) our cases have a much higher residual acid alpha-glucosidase activity and show the presence of an antigenically detectable protein. From our study and from a similar report in the literature (de Barsy et al., 1975), it appears that a combined approach of light microscopy, electron microscopy and biochemical analysis (determination of acid alpha-glucosidase) is necessary to make a diagnosis of AMD in adults.

Topics: Adult; Diseases in Twins; Female; Fibroblasts; Glucosidases; Glycogen; Glycogen Storage Disease; Glycogen Storage Disease Type II; Glycoside Hydrolases; Humans; Male; Muscles; Muscular Atrophy; Pregnancy; Skin; Twins, Dizygotic

During reconstructive procedures performed 4--16 weeks after the tendon lesion the specimens obtained from the injured muscle have been examined by the authors. It was found that after the tendon injury inactivity atrophy develops and a condition of equilibrum could be observed at this time. The most important changes in the fine structure were seen in the contractile elements: there were atrophied, homogenized, fragmentated and ragged independently from the functional unities. The number of the mitochondria was considerably decreased, the sarcoplasmatic reticulum was increased, and the difference between the originally red and white muscular fibres was indistinct. The glycogen content of the musculature was decreased, or it disappeared completely. No pathological changes have been observed in the sarcolemme, the cell nuclei and the motor nerve end-plates.

Topics: Adolescent; Adult; Cell Nucleus; Female; Glycogen; Hand; Humans; Male; Microscopy, Electron; Middle Aged; Mitochondria, Muscle; Motor Endplate; Muscles; Muscular Atrophy; Sarcoplasmic Reticulum; Tendon Injuries; Time Factors

Histochemical and histopathological staining methods were applied to muscle biopsy material from 13 patients with distal myopathy of late onset. Six cases showed slight to moderate histopathological changes and the normal distinction between Type I and Type II muscle fibres, based on their staining characteristics for myofibrillar ATPase, was well preserved. A selective Type I atrophy and an irregular distribution of oxidative enzyme and fat staining in Type I fibres were evident. In the other 7 cases, with moderate to advanced histopathological changes, there was a marked blurring of the normal difference observed in ATPase activity between Type I and TYpe II fibres. Thus, both types of fibre exhibited a high intensity of staining for myofibrillar ATPase at pH 9.4 without inhibition by acid preincubation (pH 4.3). These changes in phosphatase activity were found not only in atrophic fibres but also in normal-sized fibres without other signs of degeneration. Nuclear proliferation in chains and "ring fibres" were found. The early histopathological and histochemical changes in distal myopathy are strikingly similar to those of myotonic dystrophy.

Topics: Adenosine Triphosphatases; Adult; Aged; Cell Nucleus; Electromyography; Female; Glycogen; Humans; Lipid Metabolism; Male; Middle Aged; Muscles; Muscular Atrophy; Myofibrils; NADH Tetrazolium Reductase; Phosphorylases; Syndrome

An 11-year old boy had had recurrent episodes of hepatic and cerebral dysfunction and underdeveloped musculature. Overt weakness developed at age 10. Lipid excess, especially in type I fibers, was found in muscle. Hypertrophied smooth endoplasmic reticulum and excessive microbodies were present in liver. Marked carnitine deficiency was shown in skeletal muscle, plasma, and liver. Ketogenesis was impaired on a high fat diet, but omega oxidation of fatty acids was enhanced. There was excessive glucose uptake and essentially no oxidation of labeled long-chain fatty acids by perfused forearm muscles in vivo. Oral replacement therapy restored plasma carnitine levels to normal, but not liver or muscle carnitine levels, and was accompanied by clinical improvement.

Topics: Adenosine Triphosphatases; Betaine; Carnitine; Child; Endoplasmic Reticulum; Forearm; Glycogen; Histocytochemistry; Humans; Lipid Metabolism; Liver; Male; Microscopy, Electron; Mitochondria, Muscle; Mixed Function Oxygenases; Muscles; Muscular Atrophy; Muscular Diseases; NADH, NADPH Oxidoreductases; Oxidoreductases

The authors describe in biopsies from 6 cases of Werdnig-Hoffmann disease, including 2 of the more benign type, the ultrastructural typical aspects of denervation. They compare their findings with those of other workers. The striking points are the great variation in the diameter of the muscle fibres and the myofibrils, the disorganisation of the myofibrils, the sarcomeres and the filaments, with persistance of the relations between thick and thin filaments at various levels, the modifications of the Z-band and the triads in chains. The folds and the basement membrane are examined. Centrioles are present in a muscle fibre and in a satellite. Glycogen is very abundant. The nerves seem normal but some Schwann cells contain pi granules which are not observed usually at the age of the patient. The end plates and a muscle spindle are normal.

Topics: Basement Membrane; Cell Membrane; Child, Preschool; Cytoplasmic Granules; Demyelinating Diseases; Female; Glycogen; Humans; Infant; Male; Motor Endplate; Motor Neurons; Muscles; Muscular Atrophy; Myofibrils; Nerve Degeneration; Peripheral Nerves; Sarcoplasmic Reticulum; Syndrome

Topics: Animals; Cell Membrane Permeability; DNA; Glycogen; Haplorhini; Hypertrophy; L-Lactate Dehydrogenase; Lactates; Lipid Metabolism; Macaca; Muscle Denervation; Muscle Proteins; Muscles; Muscular Atrophy; Pyruvates; RNA; Species Specificity

Topics: Adenosine Triphosphatases; Animals; Casts, Surgical; Cell Membrane; Collagen; Cytoplasmic Granules; Glycogen; Guinea Pigs; Hydroxyproline; Immobilization; Male; Mitochondria; Muscles; Muscular Atrophy; Myofibrils; Myosins; Sarcoplasmic Reticulum; Succinate Dehydrogenase

Topics: Aged; Brain; Carbohydrate Metabolism, Inborn Errors; Dementia; Electroencephalography; Female; Glycogen; Histocytochemistry; Humans; Muscles; Muscular Atrophy; Peripheral Nerves; Spinal Cord; Syndrome; Tremor

Topics: Animals; Cats; Electric Stimulation; Electrophysiology; Glycogen; Histocytochemistry; Humans; Male; Muscle Contraction; Muscle Denervation; Muscles; Muscular Atrophy; Neuromuscular Junction; Oxidoreductases; Quadriplegia; Rabbits; Self-Help Devices; Spinal Cord; Time Factors

Topics: Acid Phosphatase; Biopsy; Child; Glucosidases; Glucosyltransferases; Glucuronidase; Glycogen; Glycogen Storage Disease; Hexosaminidases; Histocytochemistry; Humans; Intellectual Disability; Male; Microscopy; Microscopy, Electron; Muscles; Muscular Atrophy; Muscular Diseases

Topics: Abnormalities, Multiple; Age Determination by Skeleton; Bone and Bones; Consanguinity; Developmental Disabilities; Female; Foot; Glycogen; Growth Disorders; Hand; Humans; Infant; Intellectual Disability; Male; Microscopy, Electron; Muscles; Muscular Atrophy; Myofibrils; Nerve Degeneration; Pedigree; Rubinstein-Taybi Syndrome; Sarcoplasmic Reticulum

Topics: Biopsy; Glycogen; Histocytochemistry; Histological Techniques; Humans; Methods; Microscopy, Electron; Muscle Denervation; Muscles; Muscular Atrophy; Muscular Diseases; Paraffin

Topics: Adenosine Triphosphatases; Basement Membrane; Biopsy; Cell Membrane; Cell Nucleus; Child; Child, Preschool; Cytoplasmic Granules; Endoplasmic Reticulum; Female; Glycogen; Histocytochemistry; Humans; Lysosomes; Male; Microscopy, Electron; Middle Aged; Mitochondria, Muscle; Muscles; Muscular Atrophy; Myofibrils

Topics: Animals; Botulinum Toxins; Cell Nucleus; Glycogen; Histocytochemistry; Leg; Mice; Microscopy, Electron; Muscles; Muscular Atrophy; Myofibrils; Paralysis; Sarcolemma

Topics: Adolescent; Adult; Aged; Child; Demyelinating Diseases; Extremities; Female; Glycogen; Humans; Lactates; Male; Middle Aged; Muscles; Muscular Atrophy; Muscular Dystrophies; Myotonia Congenita; Myotonic Dystrophy; Paralysis; Spinal Cord Diseases

Topics: Adult; Aphonia; Child; Child, Preschool; Chronaxy; Citric Acid Cycle; Demyelinating Diseases; Energy Metabolism; Female; Glycogen; Histocytochemistry; Humans; Infant; Leukodystrophy, Metachromatic; Male; Middle Aged; Muscles; Muscular Atrophy; Nerve Degeneration; Syndrome

Topics: Adolescent; Adult; Biopsy; Cell Nucleus; Child, Preschool; Endoplasmic Reticulum; Female; Glycogen; Humans; Male; Microscopy, Electron; Mitochondria, Muscle; Muscles; Muscular Atrophy; Myofibrils; Sarcolemma

Topics: Adolescent; Amyotrophic Lateral Sclerosis; Animals; Biopsy; Cats; Dermatomyositis; Esterases; Female; Glucosyltransferases; Glycogen; Guinea Pigs; Histocytochemistry; Humans; Male; Muscular Atrophy; Muscular Diseases; Muscular Dystrophies; Myofibrils; Nervous System Diseases; Oxidoreductases; Paralysis; Rabbits; Schwann Cells; Staining and Labeling; Transferases; Tyrosine

Topics: Adolescent; Adult; Aged; Biopsy; Cell Nucleus; Cerebrovascular Disorders; Cytoplasm; Female; Glycogen; Humans; Lysosomes; Male; Microscopy, Electron; Middle Aged; Mitochondria, Muscle; Muscles; Muscular Atrophy; Neoplasms, Nerve Tissue; Sarcoplasmic Reticulum

Topics: Adult; Basement Membrane; Biopsy; Chlorides; Diabetes Complications; Diabetes Mellitus; Edema; Glycogen; Humans; Magnesium; Methods; Microscopy, Electron; Middle Aged; Muscle Proteins; Muscles; Muscular Atrophy; Muscular Diseases; Phosphorus; Potassium; Sodium

Topics: Animals; Biopsy; Cats; Female; Glycogen; Histocytochemistry; Laminectomy; Microscopy, Electron; Muscle Denervation; Muscles; Muscular Atrophy; Myofibrils; Neuromuscular Junction; Oxidoreductases; Sciatic Nerve; Spinal Cord; Spinal Nerves; Transferases

Topics: Age Factors; Child; Cytoplasm; Fluorine; Glucocorticoids; Glycogen; Golgi Apparatus; Humans; Infant; Male; Microscopy, Electron; Mitochondria, Muscle; Muscles; Muscular Atrophy; Myofibrils; Time Factors

Topics: Animals; Glycogen; Histocytochemistry; Methods; Motor Neurons; Muscle Denervation; Muscles; Muscular Atrophy; Neuromuscular Junction; Rats; Sciatic Nerve; Succinate Dehydrogenase

Topics: Adult; Aged; Antibodies; Child; Culture Techniques; Dermatomyositis; Female; Glycogen; Humans; Lymphocyte Activation; Lymphocytes; Male; Metabolic Diseases; Middle Aged; Muscles; Muscular Atrophy; Muscular Diseases; Muscular Dystrophies

Topics: Biopsy; Electroencephalography; Electromyography; Electrophoresis; Female; Glycogen; Herpes Zoster; Humans; Inclusion Bodies, Viral; Male; Microscopy, Electron; Middle Aged; Mitochondria; Muscles; Muscular Atrophy; Myofibrils; Myositis

Topics: Animals; Castration; Cell Nucleolus; Glycogen; Hypertrophy; Male; Microscopy, Electron; Muscles; Muscular Atrophy; Myofibrils; Nitrogen; Pelvis; Rats; Regeneration; Testosterone

Topics: Glycogen; Humans; Muscles; Muscular Atrophy; Muscular Dystrophies; Nitrogen; Oxygen Consumption; Potassium

Topics: Child; Child, Preschool; Citrates; Diagnosis, Differential; Female; Glycogen; Humans; Lactates; Male; Muscular Atrophy; Muscular Diseases; Muscular Dystrophies; Poliomyelitis; Pyruvates

Topics: Glycogen; Humans; Hypokalemia; Muscle Spindles; Muscular Atrophy; Muscular Diseases; Muscular Dystrophies; Myofibrils; Myositis; Paralysis; Polymyalgia Rheumatica

Topics: Adolescent; Adult; Child; Female; Glycogen; Histocytochemistry; Humans; Male; Muscular Atrophy; Muscular Dystrophies

Topics: Animals; Ascorbic Acid; Biological Transport, Active; Glycogen; In Vitro Techniques; Muscle Denervation; Muscles; Muscular Atrophy; Rats; Subcellular Fractions

Topics: Animals; Birds; Columbidae; Glycogen; Histocytochemistry; Muscles; Muscular Atrophy; Muscular Disorders, Atrophic; Phosphorylases; Phosphotransferases; Research

Topics: Adenine Nucleotides; Adenosine Triphosphate; Adolescent; Blood Chemical Analysis; Child; Coenzymes; Creatine; Creatinine; Fructose-Bisphosphate Aldolase; Glycogen; Humans; Muscular Atrophy; Muscular Diseases; Muscular Dystrophies; Pathology; Phosphates

Topics: Glycogen; Humans; Muscles; Muscular Atrophy; Paralysis; Spinal Cord

Topics: Glycogen; Muscles; Muscular Atrophy; Musculoskeletal Physiological Phenomena; Potassium