Increased muscle fatigability in GLUT-4-deficient mice

2002 ◽  
Vol 282 (2) ◽  
pp. E348-E354 ◽  
Author(s):  
M. Gorselink ◽  
M. R. Drost ◽  
K. F. J. de Brouwer ◽  
G. Schaart ◽  
G. P. J. van Kranenburg ◽  
...  
Keyword(s):  
Peak Power ◽  
Fiber Type ◽  
Flexor Muscle ◽  
Glut 4 ◽  
Muscle Complex ◽  
Alternative Routes ◽  
Deficient Mice ◽  
Shortening Contractions ◽  
Contractile Performance

GLUT-4 plays a predominant role in glucose uptake during muscle contraction. In the present study, we have investigated in mice whether disruption of the GLUT-4 gene affects isometric and shortening contractile performance of the dorsal flexor muscle complex in situ. Moreover, we have explored the hypothesis that lack of GLUT-4 enhances muscle fatigability. Isometric performance normalized to muscle mass during a single tetanic contraction did not differ between wild-type (WT) and GLUT-4-deficient [GLUT-4(−/−)] mice. Shortening contractions, however, revealed a significant 1.4-fold decrease in peak power per unit mass, most likely caused by the fiber-type transition from fast-glycolytic fibers (IIB) to fast-oxidative fibers (IIA) in GLUT-4(−/−) dorsal flexors. In addition, the resting glycogen content was significantly lower (34%) in the dorsal flexor complex of GLUT-4(−/−) mice than in WT mice. Moreover, the muscle complex of GLUT-4(−/−) mice showed enhanced susceptibility to fatigue, which may be related to the decline in the muscle carbohydrate store. The significant decrease in relative work output during the steady-state phase of the fatigue protocol suggests that energy supply via alternative routes is not capable to compensate fully for the lack of GLUT-4.

Accurate assessment of in situ isometric contractile properties of hindlimb plantar and dorsal flexor muscle complex of intact mice

2000 ◽  
Vol 439 (5) ◽  
pp. 665-670 ◽  
Author(s):  
M. Gorselink ◽  
M.R. Drost ◽  
J. de Louw ◽  
P.J.B. Willems ◽  
N. Rosielle ◽  
...  
Keyword(s):  
Contractile Properties ◽  
Accurate Assessment ◽  
Flexor Muscle ◽  
Muscle Complex

Accurate assessment of in situ isometric contractile properties of hindlimb plantar and dorsal flexor muscle complex of intact mice

2000 ◽  
Vol 439 (5) ◽  
pp. 665-670 ◽  
Author(s):  
M. Gorselink ◽  
M.R. Drost ◽  
J. de Louw ◽  
P.J.B. Willems ◽  
N. Rosielle ◽  
...  
Keyword(s):  
Contractile Properties ◽  
Accurate Assessment ◽  
Flexor Muscle ◽  
Muscle Complex

scholarly journals Fiber-type susceptibility to eccentric contraction-induced damage of hindlimb-unloaded rat AL muscles

2001 ◽  
Vol 90 (3) ◽  
pp. 770-776 ◽  
Author(s):  
K. Vijayan ◽  
J. L. Thompson ◽  
K. M. Norenberg ◽  
R. H. Fitts ◽  
D. A. Riley
Keyword(s):  
Fiber Type ◽  
Motor Nerve ◽  
Eccentric Contraction ◽  
Fiber Types ◽  
Serial Sections ◽  
Hybrid Fiber ◽  
Hybrid Fibers ◽  
Semithin Sections ◽  
Adductor Longus

Slow oxidative (SO) fibers of the adductor longus (AL) were predominantly damaged during voluntary reloading of hindlimb unloaded (HU) rats and appeared explainable by preferential SO fiber recruitment. The present study assessed damage after eliminating the variable of voluntary recruitment by tetanically activating all fibers in situ through the motor nerve while applying eccentric (lengthening) or isometric contractions. Muscles were aldehyde fixed and resin embedded, and semithin sections were cut. Sarcomere lesions were quantified in toluidine blue-stained sections. Fibers were typed in serial sections immunostained with antifast myosin and antitotal myosin (which highlights slow fibers). Both isometric and eccentric paradigms caused fatigue. Lesions occurred only in eccentrically contracted control and HU muscles. Fatigue did not cause lesions. HU increased damage because lesioned- fiber percentages within fiber types and lesion sizes were greater than control. Fast oxidative glycolytic (FOG) fibers were predominantly damaged. In no case did damaged SO fibers predominate. Thus, when FOG, SO, and hybrid fibers are actively lengthened in chronically unloaded muscle, FOG fibers are intrinsically more susceptible to damage than SO fibers. Damaged hybrid-fiber proportions ranged between these extremes.

Contraction-by-contraction V̇o2 and computer-controlled pump perfusion as novel techniques to study skeletal muscle metabolism in situ

2010 ◽  
Vol 108 (3) ◽  
pp. 705-712 ◽  
Author(s):  
Andrés Hernández ◽  
Matthew L. Goodwin ◽  
Nicola Lai ◽  
Marco E. Cabrera ◽  
James R. McDonald ◽  
...  
Keyword(s):  
Blood Flow ◽  
Moving Average ◽  
Computer Software ◽  
Muscle Metabolism ◽  
New Techniques ◽  
Muscle Oxygen ◽  
Flow Adjustment ◽  
Train Duration ◽  
Muscle Complex

The purpose of this research was to develop new techniques to 1) rapidly sample venous O2 saturation to determine contraction-by-contraction oxygen uptake (V̇o2), and 2) precisely control the rate and pattern of blood flow adjustment from one chosen steady state to another. An indwelling inline oximeter probe connected to an Oximetrix 3 meter was used to sample venous oxygen concentration ([O2]) (via fractional saturation of Hb with O2). Data from the Oximetrix 3 were filtered, deconvolved, and processed by a moving average second by second. Computer software and a program written in-house were used to control blood flow with a peristaltic pump. The isolated canine gastrocnemius muscle complex (GS) in situ was utilized to test these techniques. A step change in metabolic rate was elicited by stimulating GS muscles via their sciatic nerves (supramaximal voltage, 8 V; 50 Hz, 0.2-ms pulse width; train duration 200 ms) at a rate of either 1 contraction/2 s, or 2 contractions/3 s. With arterial [O2] maintained constant, blood flow and calculated venous [O2] were averaged over each contraction cycle and used in the Fick equation to calculate contraction-by-contraction V̇o2. About 5–8 times more data points were obtained with this method compared with traditional manual sampling. Software-controlled pump perfusion enabled the ability to mimic spontaneous blood flow on-kinetics (τ: 14.3 s) as well as dramatically speed (τ: 2.0 s) and slow (τ: 63.3 s) on-kinetics. These new techniques significantly improve on existing methods for mechanistically altering blood flow kinetics as well as accurately measuring muscle oxygen consumption kinetics during transitions between metabolic rates.

scholarly journals Upregulation of Cardiac IL-10 and Downregulation of IFN-γin Balb/c IL-4−/−in Acute Chagasic Myocarditis due to Colombian Strain ofTrypanosoma cruzi

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Marcos Vinicius da Silva ◽  
Vera Lúcia de Almeida ◽  
Wendyson Duarte de Oliveira ◽  
Natália Carasek Matos Cascudo ◽  
Pollyana Guimarães de Oliveira ◽  
...  
Keyword(s):  
Acute Phase ◽  
Experimental Infection ◽  
Cardiac Tissue ◽  
Histopathological Analysis ◽  
Nest Density ◽  
Cytokine Levels ◽  
Splenic Cells ◽  
Immune System Regulation ◽  
Deficient Mice

Inflammatory response in Chagas disease is related to parasite and host factors. However, immune system regulation has not been fully elucidated. Thus, this study is aimed at evaluating IL-4 influence on acute phase ofTrypanosoma cruziexperimental infection through dosage of cytokine levels in cardiac homogenate of infected Balb/c WT and Balb/c IL-4−/−as well as its histopathological repercussions. For such purpose, mice were divided into two groups: an infected group with 100 forms of the Colombian strain and an uninfected group. After 21 days of infection, animals were euthanized and the blood, spleen, and heart were collected. The spleen was used to culture splenic cells in 48 h. Subsequently, cytokines TNF-α, IL-12p70, IL-10, IFN-γ, and IL-17 were measured in the blood, culture supernatant, and heart apex by ELISA. The base of the heart was used for histopathological analysis. From these analysis, infected Balb/c IL-4−/−mice showed milder inflammatory infiltrate compared to Balb/c WT, but without changes in nest density and collagen deposition. IL-4 absence culminated in lower cardiac tissue IFN-γproduction, although it did not affect TNF-αexpression in situ. It also decreased TNF-αsystemic production and increased IL-10, both systemically andin situ. In addition, IL-4 absence did not influence IL-17 expression. Splenocytes of IL-4-deficient mice produced higher amounts of IFN-γ, TNF-α, and IL-17 and lower amounts of IL-10. Thus, IL-4 absence in acute phase of experimental infection withT. cruziColombian strain reduces myocarditis due to lower IFN-γproduction and greater IL-10 productionin situand this pattern is not influenced by splenocyte general repertoire.

Glucose transporter protein content and glucose transport capacity in rat skeletal muscles

1990 ◽  
Vol 259 (4) ◽  
pp. E593-E598 ◽  
Author(s):  
E. J. Henriksen ◽  
R. E. Bourey ◽  
K. J. Rodnick ◽  
L. Koranyi ◽  
M. A. Permutt ◽  
...  
Keyword(s):  
Protein Content ◽  
Glucose Transport ◽  
Glucose Transporter ◽  
Contractile Activity ◽  
Fiber Type ◽  
Linear Regression Analysis ◽  
Type I ◽  
Fiber Types ◽  
Transport Activity ◽  
Glut 4

The relationships among fiber type, glucose transporter (GLUT-4) protein content, and glucose transport activity stimulated maximally with insulin and/or contractile activity were studied by use of the rat epitrochlearis (15% type I-20% type II2a-65% type IIb), soleus (84-16-0%), extensor digitorum longus (EDL, 3-57-40%), and flexor digitorum brevis (FDB, 7-92-1%) muscles. Insulin-stimulated 2-deoxy-D-glucose (2-DG) uptake was greatest in the soleus, followed (in order) by the FDB, EDL, and epitrochlearis. On the other hand, contractile activity induced the greatest increase in 2-DG uptake in the FDB, followed by the EDL, soleus, and epitrochlearis. The effects of insulin and contractile activity on 2-DG uptake were additive in all the muscle preparations, with the relative rates being FDB greater than soleus greater than EDL greater than epitrochlearis. Quantitation of the GLUT-4 protein content with the antiserum R820 showed the following pattern: FDB greater than soleus greater than EDL greater than epitrochlearis. Linear regression analysis showed that whereas a relatively low and nonsignificant correlation existed between GLUT-4 protein content and 2-DG uptake stimulated by insulin alone, significant correlations existed between GLUT-4 protein content and 2-DG uptake stimulated either by contractions alone (r = 0.950) or by insulin and contractions in combination (r = 0.992). These results suggest that the differences in maximally stimulated glucose transport activity among the three fiber types may be related to differences in their content of GLUT-4 protein.

scholarly journals Metformin Reverses the Enhanced Myocardial SR/ER–Mitochondria Interaction and Impaired Complex I-Driven Respiration in Dystrophin-Deficient Mice

2021 ◽  
Vol 8 ◽  
Author(s):  
Claire Angebault ◽  
Mathieu Panel ◽  
Mathilde Lacôte ◽  
Jennifer Rieusset ◽  
Alain Lacampagne ◽  
...  
Keyword(s):  
Complex I ◽  
Early Stage ◽  
Intrinsic Activity ◽  
Proximity Ligation Assay ◽  
Proximity Ligation ◽  
Skeletal Muscle Dysfunction ◽  
Species Production ◽  
Therapeutic Perspective ◽  
Deficient Mice

Besides skeletal muscle dysfunction, Duchenne muscular dystrophy (DMD) exhibits a progressive cardiomyopathy characterized by an impaired calcium (Ca2+) homeostasis and a mitochondrial dysfunction. Here we aimed to determine whether sarco-endoplasmic reticulum (SR/ER)–mitochondria interactions and mitochondrial function were impaired in dystrophic heart at the early stage of the pathology. For this purpose, ventricular cardiomyocytes and mitochondria were isolated from 3-month-old dystrophin-deficient mice (mdx mice). The number of contacts points between the SR/ER Ca2+ release channels (IP3R1) and the porine of the outer membrane of the mitochondria, VDAC1, measured using in situ proximity ligation assay, was greater in mdx cardiomyocytes. Expression levels of IP3R1 as well as the mitochondrial Ca2+ uniporter (MCU) and its regulated subunit, MICU1, were also increased in mdx heart. MICU2 expression was however unchanged. Furthermore, the mitochondrial Ca2+ uptake kinetics and the mitochondrial Ca2+ content were significantly increased. Meanwhile, the Ca2+-dependent pyruvate dehydrogenase phosphorylation was reduced, and its activity significantly increased. In Ca2+-free conditions, pyruvate-driven complex I respiration was decreased whereas in the presence of Ca2+, complex I-mediated respiration was boosted. Further, impaired complex I-mediated respiration was independent of its intrinsic activity or expression, which remains unchanged but is accompanied by an increase in mitochondrial reactive oxygen species production. Finally, mdx mice were treated with the complex I modulator metformin for 1 month. Metformin normalized the SR/ER-mitochondria interaction, decreased MICU1 expression and mitochondrial Ca2+ content, and enhanced complex I-driven respiration. In summary, before any sign of dilated cardiomyopathy, the DMD heart displays an aberrant SR/ER-mitochondria coupling with an increase mitochondrial Ca2+ homeostasis and a complex I dysfunction. Such remodeling could be reversed by metformin providing a novel therapeutic perspective in DMD.

scholarly journals Percutaneous transhepatic hemodialysis catheters in chronic hemodialysis patients: technique, functional outcome, and complications from a large population study

2019 ◽  
Vol 50 (1) ◽  
Author(s):  
Osama Abuel Naga Khallaf ◽  
Karim A. Abd El Tawab ◽  
Hazem Ibrahim Korashi ◽  
Ghada Samir Ibrahim ◽  
Rasha Samir Mohamed
Keyword(s):  
Large Population ◽  
Vena Cava ◽  
Renal Dialysis ◽  
Venous Access ◽  
Chronic Hemodialysis ◽  
Dialysis Catheter ◽  
Technical Success ◽  
Exit Site Infection ◽  
Alternative Routes

Abstract Background Chronic renal failure is one of the main health problems in Egypt. Arterio-venous fistulas, grafts, as well as conventional sites for placement of the dialysis catheters are liable to thrombosis; stenosis, and occlusions, so alternative routes are considered as life-saving ways in such cases. Transhepatic permcath is one of the new and up to date methods for inferior vena cava and right atrium catheterization. Few studies with rather limited nomber are available to evaluate transhepatic permcath. The aim of our study is to emphasize the technique, complications, and efficacy of application of percutaneous transhepatic hemodialysis catheters. Results Two hundred-ninety six chronic renal dialysis patients were included in this prospective interventional study. They include 180 males and 116 females with mean age of 53.2 years ± 11.7 years ranging from 38 to 65 years. Percutaneous transhepatic hemodialysis catheters were inserted for all patients. Technical success of the procedure was achieved in all cases (100%). Post-procedure patency and function of the catheters were followed up with mean follow-up period 750 days. Mean of primary and secondary devices service intervals were 290 and 270 days respectively. Mean time catheter in situ was 280 days. Mean cumulative duration of catheter in situ was 557 days. Catheters migration, sepsis, thrombosis, and exit site infection rates were 0.14, 0.15, 0.18, and 0.32 per 100 catheter-days respectively. Three patients had hepatic subcapsular hematoma (1%). No mortality or other complications were related to the procedure. Conclusions Combined ultrasound and fluoroscopic-guided transhepatic permanent dialysis catheter application for patients with exhausted classic venous access routes and non-functioning/thrombosed AV fistulas or grafts showed excellent technical success with good short and mid-term patency rates and low complications rates. Thus, this study encourages us to expand this promising technique for application of dialysis catheter in indicated cases.

scholarly journals The cross-bridge cycle and skeletal muscle fatigue

2008 ◽  
Vol 104 (2) ◽  
pp. 551-558 ◽  
Author(s):  
Robert H. Fitts
Keyword(s):  
Peak Power ◽  
Molecular Mechanisms ◽  
Fiber Type ◽  
Low Ph ◽  
Forward Rate ◽  
Maximal Velocity ◽  
Functional Changes ◽  
Cross Bridge ◽  
The Cross

The functional correlates of fatigue observed in both animals and humans during exercise include a decline in peak force (P0), maximal velocity, and peak power. Establishing the extent to which these deleterious functional changes result from direct effects on the myofilaments is facilitated through understanding the molecular mechanisms of the cross-bridge cycle. With actin-myosin binding, the cross-bridge transitions from a weakly bound low-force state to a strongly bound high-force state. Low pH reduces the number of high-force cross bridges in fast fibers, and the force per cross bridge in both fast and slow fibers. The former is thought to involve a direct inhibition of the forward rate constant for transition to the strong cross-bridge state. In contrast, inorganic phosphate (Pi) is thought to reduce P0 by accelerating the reversal of this step. Both H+ and Pi decrease myofibrillar Ca2+ sensitivity. This effect is particularly important as the amplitude of the Ca2+ transient falls with fatigue. The inhibitory effects of low pH and high Pi on P0 are reduced as temperature increases from 10 to 30°C. However, the H+-induced depression of peak power in the slow fiber type, and Pi inhibition of myofibrillar Ca2+ sensitivity in slow and fast fibers, are greater at high compared with low temperature. Thus the depressive effects of H+ and Pi at in vivo temperatures cannot easily be predicted from data collected below 25° C. In vitro, reactive oxygen species reduce myofibrillar Ca2+ sensitivity; however, the importance of this mechanism during in vivo exercise is unknown.

The hem of the embryonic cerebral cortex is defined by the expression of multiple Wnt genes and is compromised in Gli3-deficient mice

Development ◽  
1998 ◽  
Vol 125 (12) ◽  
pp. 2315-2325 ◽  
Author(s):  
E.A. Grove ◽  
S. Tole ◽  
J. Limon ◽  
L. Yip ◽  
C.W. Ragsdale
Keyword(s):  
Gene Expression ◽  
Cerebral Cortex ◽  
Choroid Plexus ◽  
Gene Families ◽  
Cubitus Interruptus ◽  
Embryonic Mouse ◽  
Developmental Relationship ◽  
Cortical Hem ◽  
Deficient Mice

In the developing vertebrate CNS, members of the Wnt gene family are characteristically expressed at signaling centers that pattern adjacent parts of the neural tube. To identify candidate signaling centers in the telencephalon, we isolated Wnt gene fragments from cDNA derived from embryonic mouse telencephalon. In situ hybridization experiments demonstrate that one of the isolated Wnt genes, Wnt7a, is broadly expressed in the embryonic telencephalon. By contrast, three others, Wnt3a, 5a and a novel mouse Wnt gene, Wnt2b, are expressed only at the medial edge of the telencephalon, defining the hem of the cerebral cortex. The Wnt-rich cortical hem is a transient, neuron-containing, neuroepithelial structure that forms a boundary between the hippocampus and the telencephalic choroid plexus epithelium (CPe) throughout their embryonic development. Indicating a close developmental relationship between the cortical hem and the CPe, Wnt gene expression is upregulated in the cortical hem both before and just as the CPe begins to form, and persists until birth. In addition, although the cortical hem does not show features of differentiated CPe, such as expression of transthyretin mRNA, the CPe and cortical hem are linked by shared expression of members of the Bmp and Msx gene families. In the extra-toesJ (XtJ) mouse mutant, telencephalic CPe fails to develop. We show that Wnt gene expression is deficient at the cortical hem in XtJ/XtJ mice, but that the expression of other telencephalic developmental control genes, including Wnt7a, is maintained. The XtJ mutant carries a deletion in Gli3, a vertebrate homolog of the Drosophila gene cubitus interruptus (ci), which encodes a transcriptional regulator of the Drosophila Wnt gene, wingless. Our observations indicate that Gli3 participates in Wnt gene regulation in the vertebrate telencephalon, and suggest that the loss of telencephalic choroid plexus in XtJ mice is due to defects in the cortical hem that include Wnt gene misregulation.

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