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American Journal of Physiology.... Sep 2012Elevated mitochondrial reactive oxygen species have been suggested to play a causative role in some forms of muscle insulin resistance. However, the extent of their...
Elevated mitochondrial reactive oxygen species have been suggested to play a causative role in some forms of muscle insulin resistance. However, the extent of their involvement in the development of diet-induced insulin resistance remains unclear. To investigate, manganese superoxide dismutase (MnSOD), a key mitochondrial-specific enzyme with antioxidant modality, was overexpressed, and the effect on in vivo muscle insulin resistance induced by a high-fat (HF) diet in rats was evaluated. Male Wistar rats were maintained on chow or HF diet. After 3 wk, in vivo electroporation (IVE) of MnSOD expression and empty vectors was undertaken in right and left tibialis cranialis (TC) muscles, respectively. After one more week, insulin action was evaluated using hyperinsulinemic euglycemic clamp, and tissues were subsequently analyzed for antioxidant enzyme capacity and markers of oxidative stress. MnSOD mRNA was overexpressed 4.5-fold, and protein levels were increased by 70%, with protein detected primarily in the mitochondrial fraction of muscle fibers. This was associated with elevated MnSOD and glutathione peroxidase activity, indicating that the overexpressed MnSOD was functionally active. The HF diet significantly reduced whole body and TC muscle insulin action, whereas overexpression of MnSOD in HF diet animals ameliorated this reduction in TC muscle glucose uptake by 50% (P < 0.05). Decreased protein carbonylation was seen in MnSOD overexpressing TC muscle in HF-treated animals (20% vs. contralateral control leg, P < 0.05), suggesting that this effect was mediated through an altered redox state. Thus interventions causing elevation of mitochondrial antioxidant activity may offer protection against diet-induced insulin resistance in skeletal muscle.
Topics: Animals; Diet, High-Fat; Electroporation; Gene Transfer Techniques; Glutathione Peroxidase; Humans; Insulin Resistance; Lower Extremity; Male; Mitochondria, Muscle; Muscle Fibers, Skeletal; Muscle, Skeletal; Oxidative Stress; Protein Carbonylation; RNA, Messenger; Rats; Rats, Wistar; Recombinant Fusion Proteins; Superoxide Dismutase; Up-Regulation
PubMed: 22829583
DOI: 10.1152/ajpendo.00577.2011 -
British Journal of Anaesthesia Aug 1999We have noted previously that duration of vecuronium block correlated with fibre size in six muscle groups in the goat. Electrophysiological considerations suggest that...
We have noted previously that duration of vecuronium block correlated with fibre size in six muscle groups in the goat. Electrophysiological considerations suggest that the important factor should be the number of acetylcholine receptors (AChR) relative to fibre size. However, this hypothesis could not be verified in the goat because the number of AChR was relatively constant in the different muscles despite differences in fibre size. Therefore, in this study, we have investigated the relationship between sensitivity to vecuronium, as reflected by the ED50 and duration of block, of six muscles in the cat and the number of AChR per unit fibre cross-sectional area (CSA). The ED50 and duration of action (time to 50% recovery of the first twitch after a dose of 15 micrograms kg-1) of vecuronium in the tibialis cranialis, soleus, rectus abdominis, masseter, diaphragm and thyroarytenoideus muscles were determined during train-of-four stimulation and EMG recording in seven cats anaesthetized with pentobarbital. CSA of the muscle fibres and number of junctional AChR in these muscles were measured by histological methods and 125I-alpha-bungarotoxin binding assay, respectively, and the number of AChR per unit fibre CSA calculated. The association between muscle response (ED50 and duration of block) and fibre CSA or number of AChR per unit fibre CSA was then tested by regression analyses. Duration of block varied between the six muscles (mean 8.9 (SEM 2.6) to 20.3 (3.1) min; P = 0.0001) but ED50 did not (7.5 (1.5) to 15.6 (2.5) micrograms kg-1; P = 0.185). Fibre CSA and number of AChR per unit fibre CSA also varied between these muscles (P = 0.0001). Duration to 50% TI recovery was prolonged in muscles with a low number of AChR relative to fibre CSA (r2 = 0.30; P = 0.0002) and the ED50 increased as the number of AChR per fibre CSA increased (r2 = 0.240; P = 0.0016). These results in the cat suggest that the number of junctional AChR relative to fibre CSA is a morphological predictor of the differential sensitivities of muscles to neuromuscular blocking agents.
Topics: Analysis of Variance; Animals; Cats; Female; Male; Muscle Fibers, Skeletal; Muscle, Skeletal; Neuromuscular Blockade; Neuromuscular Nondepolarizing Agents; Receptors, Cholinergic; Time Factors; Vecuronium Bromide
PubMed: 10618945
DOI: 10.1093/bja/83.2.284 -
Journal of Anatomy Jul 2010Selective breeding for performance has resulted in distinct breeds of horse, such as the Quarter Horse (bred for acceleration) and the Arab (bred for endurance). Rapid... (Comparative Study)
Comparative Study
Selective breeding for performance has resulted in distinct breeds of horse, such as the Quarter Horse (bred for acceleration) and the Arab (bred for endurance). Rapid acceleration, seen during Quarter Horse racing, requires fast powerful muscular contraction and the generation of large joint torques, particularly by the hind limb muscles. This study compared hind limb moment arm lengths in the Quarter Horse and Arab. We hypothesized that Quarter Horse hind limb extensor muscles would have longer moment arms when compared to the Arab, conferring a greater potential for torque generation at the hip, stifle and tarsus during limb extension. Six Quarter Horse and six Arab hind limbs were dissected to determine muscle moment arm lengths for the following muscles: gluteus medius, biceps femoris, semitendinosus, vastus lateralis, gastrocnemius (medialis and lateralis) and tibialis cranialis. The moment arms of biceps femoris (acting at the hip) and gastrocnemius lateralis (acting at the stifle) were significantly longer in the Quarter Horse, although the length of the remaining muscle moment arms were similar in both breeds of horse. All the Quarter Horse muscles were capable of generating greater muscle moments owing to their greater physiological cross-sectional area (PCSA) and therefore greater isometric force potential, which suggests that PCSA is a better determinant of muscle torque than moment arm length in these two breeds of horse. With the exception of gastrocnemius and tibialis cranialis, the observed muscle fascicle length to moment arm ratio (MFL : MA ratio) was greater for the Arab horse muscles. It appears that the Arab muscles have the potential to operate at slower velocities of contraction and hence generate greater force outputs when compared to the Quarter Horse muscles working over a similar range of joint motion; this would indicate that Arab hind limb muscles are optimized to function at maximum economy rather than maximum power output.
Topics: Acceleration; Animals; Biometry; Breeding; Female; Hindlimb; Hip Joint; Horses; Male; Muscle Contraction; Muscle, Skeletal; Physical Endurance; Range of Motion, Articular; Torque
PubMed: 20492428
DOI: 10.1111/j.1469-7580.2010.01241.x -
Folia Morphologica Feb 2024That the peroneus tertius muscle (PT) is a separate entity has been debated. PT has been reported to be part of the extensor digitorum longus muscle, part of the...
BACKGROUND
That the peroneus tertius muscle (PT) is a separate entity has been debated. PT has been reported to be part of the extensor digitorum longus muscle, part of the extensor digitorum brevis, or a separate muscle. While pigs have a PT as well as primates, there are no reports of its association with the extensor digitorum longus muscle or extensor digitorum brevis.
MATERIALS AND METHODS
In this study, we used gross dissection and Sihler's staining to determine the origin, course, insertion, and innervation of the pig PT.
RESULTS
The PT and extensor digitorum longus muscles jointly originated from the femur and ran between the tibialis cranialis and peroneus longus muscles. The PT was inserted at the retinaculum of the metatarsal extensors, tarsal bone, and second metatarsal bone. The branches of the common fibular nerve to the extensor digitorum longus muscle were distributed to the PT.
CONCLUSIONS
The innervations suggest that the PT and extensor digitorum longus muscles of the pig were derived from the same muscle mass during development but were named separately due to differences in their morphology. Furthermore, morphological features suggest that pig PT and human PT are probably different muscles.
PubMed: 38299444
DOI: 10.5603/fm.98348 -
PloS One 2015SIRT1 is a NAD+-dependent deacetylase thought to regulate cellular metabolic pathways in response to alterations in nutrient flux. In the current study we investigated...
SIRT1 is a NAD+-dependent deacetylase thought to regulate cellular metabolic pathways in response to alterations in nutrient flux. In the current study we investigated whether acute changes in SIRT1 expression affect markers of muscle mitochondrial content and also determined whether SIRT1 influenced muscle insulin resistance induced by acute glucose oversupply. In male Wistar rats either SIRT1 or a deacetylase inactive mutant form (H363Y) was electroprated into the tibialis cranialis (TC) muscle. The other leg was electroporated with an empty control vector. One week later, glucose was infused and hyperglycaemia was maintained at ~11mM. After 5 hours, 11mM glucose induced significant insulin resistance in skeletal muscle. Interestingly, overexpression of either SIRT1 or SIRT1 (H363Y) for 1 week did not change markers of mitochondrial content or function. SIRT1 or SIRT1 (H363Y) overexpression had no effect on the reduction in glucose uptake and glycogen synthesis in muscle in response to hyperglycemia. Therefore we conclude that acute increases in SIRT1 protein have little impact on mitochondrial content and that overexpressing SIRT1 does not prevent the development of insulin resistance during hyperglycaemia.
Topics: Animals; Blood Glucose; Cell Line; Electroporation; Glucose; Hyperglycemia; Insulin Resistance; Male; Mice; Muscle, Skeletal; Rats; Rats, Wistar; Signal Transduction; Sirtuin 1
PubMed: 25798922
DOI: 10.1371/journal.pone.0121959 -
American Journal of Physiology.... Apr 2012Serum levels and muscle expression of the chemokine CXCL1 increase markedly in response to exercise in mice. Because several studies have established muscle-derived...
Serum levels and muscle expression of the chemokine CXCL1 increase markedly in response to exercise in mice. Because several studies have established muscle-derived factors as important contributors of metabolic effects of exercise, this study aimed at investigating the effect of increased expression of muscle-derived CXCL1 on systemic and intramuscular metabolic parameters, with focus on fatty acid oxidation and oxidative metabolism in skeletal muscle. By overexpression of CXCL1 in the tibialis cranialis muscle in mice, significant elevations in muscle and serum CXCL1 within a physiological range were obtained. At 3 mo of high-fat feeding, visceral and subcutaneous fat mass were 32.4 (P < 0.01) and 22.4% (P < 0.05) lower, respectively, in CXCL1-overexpressing mice compared with control mice. Also, chow-fed CXCL-transfected mice had 35.4% (P < 0.05) lower visceral fat mass and 33.4% (P < 0.05) lower subcutaneous fat mass compared with chow-fed control mice. These reductions in accumulation of adipose tissue were accompanied by improved glucose tolerance and insulin sensitivity. Furthermore, in CXCL1-transfected muscles, muscular ex vivo fatty acid oxidation was significantly enhanced compared with control muscles (chow fed: 2.2-fold, P < 0.05; high-fat fed: 2-fold, P < 0.05) and also showed increased expression levels of major fatty acid oxidation genes (CD36, CPT I, and HADH). Finally, CXCL1 expression was associated with increased muscle mRNA expression of VEGF and CD31, suggesting a role for CXCL1 in muscle angiogenesis. In conclusion, our data show that overexpression of CXCL1 within a physiological range attenuates diet-induced obesity, likely mediated through a CXCL1-induced improvement of fatty acid oxidation and oxidative capacity in skeletal muscle tissue.
Topics: Adipose Tissue; Animals; Body Composition; Body Weight; Chemokine CXCL1; Cytokines; DNA; Diet; Eating; Fatty Acids, Nonesterified; Glucose Tolerance Test; Mice; Mice, Inbred C57BL; Muscle Proteins; Muscle, Skeletal; Neovascularization, Physiologic; Obesity; Oxidation-Reduction; Platelet Endothelial Cell Adhesion Molecule-1; Real-Time Polymerase Chain Reaction; Transfection; Up-Regulation; Vascular Endothelial Growth Factor A
PubMed: 22275756
DOI: 10.1152/ajpendo.00339.2011 -
PloS One 2013The effect of the fast skeletal muscle troponin activator, CK-2066260, on calcium-induced force development was studied in skinned fast skeletal muscle fibers from...
The effect of the fast skeletal muscle troponin activator, CK-2066260, on calcium-induced force development was studied in skinned fast skeletal muscle fibers from wildtype (WT) and nebulin deficient (NEB KO) mice. Nebulin is a sarcomeric protein that when absent (NEB KO mouse) or present at low levels (nemaline myopathy (NM) patients with NEB mutations) causes muscle weakness. We studied the effect of fast skeletal troponin activation on WT muscle and tested whether it might be a therapeutic mechanism to increase muscle strength in nebulin deficient muscle. We measured tension-pCa relations with and without added CK-2066260. Maximal active tension in NEB KO tibialis cranialis fibers in the absence of CK-2066260 was ∼60% less than in WT fibers, consistent with earlier work. CK-2066260 shifted the tension-calcium relationship leftwards, with the largest relative increase (up to 8-fold) at low to intermediate calcium levels. This was a general effect that was present in both WT and NEB KO fiber bundles. At pCa levels above ∼6.0 (i.e., calcium concentrations <1 µM), CK-2066260 increased tension of NEB KO fibers to beyond that of WT fibers. Crossbridge cycling kinetics were studied by measuring k(tr) (rate constant of force redevelopment following a rapid shortening/restretch). CK-2066260 greatly increased k(tr) at submaximal activation levels in both WT and NEB KO fiber bundles. We also studied the sarcomere length (SL) dependence of the CK-2066260 effect (SL 2.1 µm and 2.6 µm) and found that in the NEB KO fibers, CK-2066260 had a larger effect on calcium sensitivity at the long SL. We conclude that fast skeletal muscle troponin activation increases force at submaximal activation in both wildtype and NEB KO fiber bundles and, importantly, that this troponin activation is a potential therapeutic mechanism for increasing force in NM and other skeletal muscle diseases with loss of muscle strength.
Topics: Animals; Biomechanical Phenomena; Calcium; In Vitro Techniques; Kinetics; Mice; Mice, Knockout; Muscle Fatigue; Muscle Fibers, Fast-Twitch; Muscle Proteins; Sarcomeres; Troponin
PubMed: 23437068
DOI: 10.1371/journal.pone.0055861 -
American Journal of Veterinary Research Oct 2008To determine the electrical impulse duration thresholds (chronaxy) for maximal motor contraction of various muscles without stimulation of pain fibers in dogs.
OBJECTIVE
To determine the electrical impulse duration thresholds (chronaxy) for maximal motor contraction of various muscles without stimulation of pain fibers in dogs.
ANIMALS
10 healthy adult Beagles.
PROCEDURES
The dogs were used to assess the minimal intensity (rheobase) required to elicit motor contraction of 11 muscles (5 in the forelimb [supraspinatus, infraspinatus, deltoideus, lateral head of the triceps brachii, and extensor carpi radialis], 5 in the hind limb [gluteus medius, biceps femoris, semitendinosus, vastus lateralis, and tibialis cranialis], and the erector spinae). The rheobase was used to determine the chronaxy for each of the 11 muscles in the 10 dogs; chronaxy values were compared with those reported for the corresponding muscles in humans.
RESULTS
Compared with values in humans, chronaxy values for stimulation of AA motor fibers in the biceps femoris and semitendinosus muscles and muscles of the more distal portions of limbs were lower in dogs. For the other muscles evaluated, chronaxy values did not differ between dogs and humans.
CONCLUSIONS AND CLINICAL RELEVANCE
Application of the dog-specific chronaxy values when performing electrical stimulation for strengthening muscles or providing pain relief is likely to minimize the pain perceived during treatment in dogs.
Topics: Animals; Dogs; Electric Stimulation; Humans; Kinetics; Muscle Contraction; Muscle Fibers, Skeletal; Muscle, Skeletal; Sensory Thresholds; Species Specificity; Time Factors
PubMed: 18828687
DOI: 10.2460/ajvr.69.10.1305 -
Journal of Applied Physiology... May 2009Understanding the mechanical determinants of the energy cost of limb swing is crucial for refining our models of locomotor energetics, as well as improving treatments...
Understanding the mechanical determinants of the energy cost of limb swing is crucial for refining our models of locomotor energetics, as well as improving treatments for those suffering from impaired limb-swing mechanics. In this study, we use guinea fowl (Numida meleagris) as a model to explore whether mechanical work at the joints explains limb-swing energy use by combining inverse dynamic modeling and muscle-specific energetics from blood flow measurements. We found that the overall efficiencies of the limb swing increased markedly from walking (3%) to fast running (17%) and are well below the usually accepted maximum efficiency of muscle, except at the fastest speeds recorded. The estimated efficiency of a single muscle used during ankle flexion (tibialis cranialis) parallels that of the total limb-swing efficiency (3% walking, 15% fast running). Taken together, these findings do not support the hypothesis that joint work is the major determinant of limb-swing energy use across the animal's speed range and warn against making simple predictions of energy use based on joint mechanical work. To understand limb-swing energy use, mechanical functions other than accelerating the limb segments need to be explored, including isometric force production and muscle work arising from active and passive antagonist muscle forces.
Topics: Animals; Energy Metabolism; Female; Galliformes; Hindlimb; Male; Models, Biological; Muscle, Skeletal; Running; Walking
PubMed: 19228989
DOI: 10.1152/japplphysiol.91115.2008 -
Journal of Anatomy Jun 1996Morphological features and the chronology of muscle changes after denervation were studied over a 21 d period in 2 heavy (HW) and light-weight (LW) strains of 6-wk-old... (Comparative Study)
Comparative Study
Morphological features and the chronology of muscle changes after denervation were studied over a 21 d period in 2 heavy (HW) and light-weight (LW) strains of 6-wk-old male turkeys. The atrophy of tibialis cranialis, gastrocnemius lateralis and plantaris muscles was apparent at d 3 after denervation. By d 21 the weight of these muscles had reached 45-60% of that of nondenervated contralateral muscle. Cellular lesions, such as irregularities in mitochondrial distribution or coagulative necrosis with fragmentation and lysis associated with moderate infiltration of inflammatory cells, were similar in both strains. Ten days after denervation, immunolabelling of a proliferating cell nuclear antigen (PCNA) expressed during the G1 and S phase of the cell cycle revealed satellite cell activation in denervated muscles. The number of satellite cells activated at d 21 was markedly greater in the HW than LW strain. Morphometric analysis revealed that fast twitch (type II) fibres were atrophied after denervation, whereas slow-twitch (type I) and slow tonic (type III) fibres were hypertrophied from d 10. Hypertrophy occurred more rapidly in the LW than HW strain.
Topics: Animals; Body Weight; Hypertrophy; Immunohistochemistry; Inflammation; Male; Muscle Denervation; Muscle Fibers, Fast-Twitch; Muscle Fibers, Slow-Twitch; Muscle, Skeletal; Proliferating Cell Nuclear Antigen; Time Factors; Turkeys
PubMed: 8763485
DOI: No ID Found