Visualization of muscles involved in unilateral tremor using 13N-ammonia and positron emission tomography

International Nuclear Information System (INIS)

Schelstraete, K.; Simons, M.; Deman, J.; Vermeulen, F.L.; Ghent Rijksuniversiteit; Goethals, P.; Bratzlavsky, M.

1982-01-01

Using positron emission computerized tomography (PCT), a high uptake of IV injected 13 N-ammonia was observed in the muscles of the right forearm and leg of a patient with a rightsided static tremor. In some mucles the concentration of 13 NH 3 was 8.5 times higher than in the symmetrical normal limb. Confrontation of the clinical, neurological, and electroyographic findings with the results of the PCT proved that the muscles with the high uptake corresponded to the muscles responsible for the tremulous movements. There is strong evidence that the high uptake of 13 NH 3 was related to the increased blood flow produced by the continuous rhythmic exercise of the muscles involved in the tremor. To our knowledge a similar observation has not been described before. It is suggested that the combined use of suitable positron emitters and PCT might provide a valuable tool for the noninvasive study of perfusion of individual skeletal muscles. (orig.)

Rac1 is a novel regulator of contraction-stimulated glucose uptake in skeletal muscle.

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Sylow, Lykke; Jensen, Thomas E; Kleinert, Maximilian; Mouatt, Joshua R; Maarbjerg, Stine J; Jeppesen, Jacob; Prats, Clara; Chiu, Tim T; Boguslavsky, Shlomit; Klip, Amira; Schjerling, Peter; Richter, Erik A

2013-04-01

In skeletal muscle, the actin cytoskeleton-regulating GTPase, Rac1, is necessary for insulin-dependent GLUT4 translocation. Muscle contraction increases glucose transport and represents an alternative signaling pathway to insulin. Whether Rac1 is activated by muscle contraction and regulates contraction-induced glucose uptake is unknown. Therefore, we studied the effects of in vivo exercise and ex vivo muscle contractions on Rac1 signaling and its regulatory role in glucose uptake in mice and humans. Muscle Rac1-GTP binding was increased after exercise in mice (~60-100%) and humans (~40%), and this activation was AMP-activated protein kinase independent. Rac1 inhibition reduced contraction-stimulated glucose uptake in mouse muscle by 55% in soleus and by 20-58% in extensor digitorum longus (EDL; P contraction-stimulated increment in glucose uptake was decreased by 27% (P = 0.1) and 40% (P muscles, respectively, of muscle-specific inducible Rac1 knockout mice. Furthermore, depolymerization of the actin cytoskeleton decreased contraction-stimulated glucose uptake by 100% and 62% (P muscles, respectively. These are the first data to show that Rac1 is activated during muscle contraction in murine and human skeletal muscle and suggest that Rac1 and possibly the actin cytoskeleton are novel regulators of contraction-stimulated glucose uptake.

Skeletal muscle glucose uptake during exercise

DEFF Research Database (Denmark)

Rose, Adam John; Richter, Erik

2005-01-01

The increase in skeletal muscle glucose uptake during exercise results from a coordinated increase in rates of glucose delivery (higher capillary perfusion), surface membrane glucose transport, and intracellular substrate flux through glycolysis. The mechanism behind the movement of GLUT4...

Shikonin increases glucose uptake in skeletal muscle cells and improves plasma glucose levels in diabetic Goto-Kakizaki rats.

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Anette I Öberg

Full Text Available BACKGROUND: There is considerable interest in identifying compounds that can improve glucose homeostasis. Skeletal muscle, due to its large mass, is the principal organ for glucose disposal in the body and we have investigated here if shikonin, a naphthoquinone derived from the Chinese plant Lithospermum erythrorhizon, increases glucose uptake in skeletal muscle cells. METHODOLOGY/PRINCIPAL FINDINGS: Shikonin increases glucose uptake in L6 skeletal muscle myotubes, but does not phosphorylate Akt, indicating that in skeletal muscle cells its effect is medaited via a pathway distinct from that used for insulin-stimulated uptake. Furthermore we find no evidence for the involvement of AMP-activated protein kinase in shikonin induced glucose uptake. Shikonin increases the intracellular levels of calcium in these cells and this increase is necessary for shikonin-mediated glucose uptake. Furthermore, we found that shikonin stimulated the translocation of GLUT4 from intracellular vesicles to the cell surface in L6 myoblasts. The beneficial effect of shikonin on glucose uptake was investigated in vivo by measuring plasma glucose levels and insulin sensitivity in spontaneously diabetic Goto-Kakizaki rats. Treatment with shikonin (10 mg/kg intraperitoneally once daily for 4 days significantly decreased plasma glucose levels. In an insulin sensitivity test (s.c. injection of 0.5 U/kg insulin, plasma glucose levels were significantly lower in the shikonin-treated rats. In conclusion, shikonin increases glucose uptake in muscle cells via an insulin-independent pathway dependent on calcium. CONCLUSIONS/SIGNIFICANCE: Shikonin increases glucose uptake in skeletal muscle cells via an insulin-independent pathway dependent on calcium. The beneficial effects of shikonin on glucose metabolism, both in vitro and in vivo, show that the compound possesses properties that make it of considerable interest for developing novel treatment of type 2 diabetes.

Unexpected radionuclide uptake due to calcification in muscles

International Nuclear Information System (INIS)

Khier, A.

1999-01-01

Full text: A male patient aged 27 years was injected with 1000 MBq of 99 Tc m -MDP. The patient was an active man indulging in contact sport. He presented with lower back and pelvic pain. Spot pictures were made of the pelvis, lumbar spine and femurs. Unexpected active radionuclide uptake in the muscles was seen. In the delayed static images, there was focal accumulation of tracer uptake in the muscles overlying the mid-shaft of the left femur consistent with myositis ossificans. Myositis ossificans is a benign ossifying process that is generally solitary and well circumscribed. It is most commonly found in the muscles but it may occur in other connective tissues, especially tendons and subcutaneous fat. This was presumably associated with chronic muscular injuries contracted during sports activity

Rac1 Is a Novel Regulator of Contraction-Stimulated Glucose Uptake in Skeletal Muscle

Science.gov (United States)

Sylow, Lykke; Jensen, Thomas E.; Kleinert, Maximilian; Mouatt, Joshua R.; Maarbjerg, Stine J.; Jeppesen, Jacob; Prats, Clara; Chiu, Tim T.; Boguslavsky, Shlomit; Klip, Amira; Schjerling, Peter; Richter, Erik A.

2013-01-01

In skeletal muscle, the actin cytoskeleton-regulating GTPase, Rac1, is necessary for insulin-dependent GLUT4 translocation. Muscle contraction increases glucose transport and represents an alternative signaling pathway to insulin. Whether Rac1 is activated by muscle contraction and regulates contraction-induced glucose uptake is unknown. Therefore, we studied the effects of in vivo exercise and ex vivo muscle contractions on Rac1 signaling and its regulatory role in glucose uptake in mice and humans. Muscle Rac1-GTP binding was increased after exercise in mice (∼60–100%) and humans (∼40%), and this activation was AMP-activated protein kinase independent. Rac1 inhibition reduced contraction-stimulated glucose uptake in mouse muscle by 55% in soleus and by 20–58% in extensor digitorum longus (EDL; P Rac1 knockout mice. Furthermore, depolymerization of the actin cytoskeleton decreased contraction-stimulated glucose uptake by 100% and 62% (P Rac1 is activated during muscle contraction in murine and human skeletal muscle and suggest that Rac1 and possibly the actin cytoskeleton are novel regulators of contraction-stimulated glucose uptake. PMID:23274900

Involvement of atypical protein kinase C in the regulation of cardiac glucose and long-chain fatty acid uptake

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Habets, Daphna D J; Luiken, Joost J F P; Ouwens, Margriet

2012-01-01

Aim: The signaling pathways involved in the regulation of cardiac GLUT4 translocation/glucose uptake and CD36 translocation/long-chain fatty acid uptake are not fully understood. We compared in heart/muscle-specific PKC-¿ knockout mice the roles of atypical PKCs (PKC-¿ and PKC-¿) in regulating...

CaMKII regulates contraction- but not insulin-induced glucose uptake in mouse skeletal muscle.

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Witczak, Carol A; Jessen, Niels; Warro, Daniel M; Toyoda, Taro; Fujii, Nobuharu; Anderson, Mark E; Hirshman, Michael F; Goodyear, Laurie J

2010-06-01

Studies using chemical inhibitors have suggested that the Ca(2+)-sensitive serine/threonine kinase Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) is a key regulator of both insulin- and contraction-stimulated glucose uptake in skeletal muscle. However, due to nonspecificity of these inhibitors, the specific role that CaMKII may play in the regulation of glucose uptake is not known. We sought to determine whether specific inhibition of CaMKII impairs insulin- and/or contraction-induced glucose uptake in mouse skeletal muscle. Expression vectors containing green fluorescent protein conjugated to a CaMKII inhibitory (KKALHRQEAVDCL) or control (KKALHAQERVDCL) peptide were transfected into tibialis anterior muscles by in vivo electroporation. After 1 wk, muscles were assessed for peptide expression, CaMK activity, insulin- and contraction-induced 2-[(3)H]deoxyglucose uptake, glycogen concentrations, and changes in intracellular signaling proteins. Expression of the CaMKII inhibitory peptide decreased muscle CaMK activity approximately 35% compared with control peptide. Insulin-induced glucose uptake was not changed in muscles expressing the inhibitory peptide. In contrast, expression of the inhibitory peptide significantly decreased contraction-induced muscle glucose uptake (approximately 30%). Contraction-induced decreases in muscle glycogen were not altered by the inhibitory peptide. The CaMKII inhibitory peptide did not alter expression of the glucose transporter GLUT4 and did not impair contraction-induced increases in the phosphorylation of AMP-activated protein kinase (Thr(172)) or TBC1D1/TBC1D4 on phospho-Akt substrate sites. These results demonstrate that CaMKII does not regulate insulin-stimulated glucose uptake in skeletal muscle. However, CaMKII plays a critical role in the regulation of contraction-induced glucose uptake in mouse skeletal muscle.

Respiratory muscle involvement in sarcoidosis.

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Schreiber, Tina; Windisch, Wolfram

2018-07-01

In sarcoidosis, muscle involvement is common, but mostly asymptomatic. Currently, little is known about respiratory muscle and diaphragm involvement and function in patients with sarcoidosis. Reduced inspiratory muscle strength and/or a reduced diaphragm function may contribute to exertional dyspnea, fatigue and reduced health-related quality of life. Previous studies using volitional and non-volitional tests demonstrated a reduced inspiratory muscle strength in sarcoidosis compared to control subjects, and also showed that respiratory muscle function may even be significantly impaired in a subset of patients. Areas covered: This review examines the evidence on respiratory muscle involvement and its implications in sarcoidosis with emphasis on pathogenesis, diagnosis and treatment of respiratory muscle dysfunction. The presented evidence was identified by a literature search performed in PubMed and Medline for articles about respiratory and skeletal muscle function in sarcoidosis through to January 2018. Expert commentary: Respiratory muscle involvement in sarcoidosis is an underdiagnosed condition, which may have an important impact on dyspnea and health-related quality of life. Further studies are needed to understand the etiology, pathogenesis and extent of respiratory muscle involvement in sarcoidosis.

Effect of glycogen synthase overexpression on insulin-stimulated muscle glucose uptake and storage.

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Fogt, Donovan L; Pan, Shujia; Lee, Sukho; Ding, Zhenping; Scrimgeour, Angus; Lawrence, John C; Ivy, John L

2004-03-01

Insulin-stimulated muscle glucose uptake is inversely associated with the muscle glycogen concentration. To investigate whether this association is a cause and effect relationship, we compared insulin-stimulated muscle glucose uptake in noncontracted and postcontracted muscle of GSL3-transgenic and wild-type mice. GSL3-transgenic mice overexpress a constitutively active form of glycogen synthase, which results in an abundant storage of muscle glycogen. Muscle contraction was elicited by in situ electrical stimulation of the sciatic nerve. Right gastrocnemii from GSL3-transgenic and wild-type mice were subjected to 30 min of electrical stimulation followed by hindlimb perfusion of both hindlimbs. Thirty minutes of contraction significantly reduced muscle glycogen concentration in wild-type (49%) and transgenic (27%) mice, although transgenic mice retained 168.8 +/- 20.5 micromol/g glycogen compared with 17.7 +/- 2.6 micromol/g glycogen for wild-type mice. Muscle of transgenic and wild-type mice demonstrated similar pre- (3.6 +/- 0.3 and 3.9 +/- 0.6 micromol.g(-1).h(-1) for transgenic and wild-type, respectively) and postcontraction (7.9 +/- 0.4 and 7.0 +/- 0.4 micromol.g(-1).h(-1) for transgenic and wild-type, respectively) insulin-stimulated glucose uptakes. However, the [14C]glucose incorporated into glycogen was greater in noncontracted (151%) and postcontracted (157%) transgenic muscle vs. muscle of corresponding wild-type mice. These results indicate that glycogen synthase activity is not rate limiting for insulin-stimulated glucose uptake in skeletal muscle and that the inverse relationship between muscle glycogen and insulin-stimulated glucose uptake is an association, not a cause and effect relationship.

Phosphatidylinositol 3-phosphate 5-kinase (PIKfyve) is an AMPK target participating in contraction-stimulated glucose uptake in skeletal muscle.

Science.gov (United States)

Liu, Yang; Lai, Yu-Chiang; Hill, Elaine V; Tyteca, Donatienne; Carpentier, Sarah; Ingvaldsen, Ada; Vertommen, Didier; Lantier, Louise; Foretz, Marc; Dequiedt, Franck; Courtoy, Pierre J; Erneux, Christophe; Viollet, Benoît; Shepherd, Peter R; Tavaré, Jeremy M; Jensen, Jørgen; Rider, Mark H

2013-10-15

PIKfyve (FYVE domain-containing phosphatidylinositol 3-phosphate 5-kinase), the lipid kinase that phosphorylates PtdIns3P to PtdIns(3,5)P2, has been implicated in insulin-stimulated glucose uptake. We investigated whether PIKfyve could also be involved in contraction/AMPK (AMP-activated protein kinase)-stimulated glucose uptake in skeletal muscle. Incubation of rat epitrochlearis muscles with YM201636, a selective PIKfyve inhibitor, reduced contraction- and AICAriboside (5-amino-4-imidazolecarboxamide riboside)-stimulated glucose uptake. Consistently, PIKfyve knockdown in C2C12 myotubes reduced AICAriboside-stimulated glucose transport. Furthermore, muscle contraction increased PtdIns(3,5)P2 levels and PIKfyve phosphorylation. AMPK phosphorylated PIKfyve at Ser307 both in vitro and in intact cells. Following subcellular fractionation, PIKfyve recovery in a crude intracellular membrane fraction was increased in contracting versus resting muscles. Also in opossum kidney cells, wild-type, but not S307A mutant, PIKfyve was recruited to endosomal vesicles in response to AMPK activation. We propose that PIKfyve activity is required for the stimulation of skeletal muscle glucose uptake by contraction/AMPK activation. PIKfyve is a new AMPK substrate whose phosphorylation at Ser307 could promote PIKfyve translocation to endosomes for PtdIns(3,5)P2 synthesis to facilitate GLUT4 (glucose transporter 4) translocation.

F-18 FDG uptake in respiratory muscle mimicking metastasis in patients with gastric cancer

International Nuclear Information System (INIS)

Choi, Seung Jin; Hyun, In Young; Kim, Jeong Ho

2006-01-01

A 67-year-old man with a history of chronic obstructive pulmonary disease (COPD) underwent F-18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) for staging of gastric cancer. The projection images of F-18 FDG PET/CT showed intensely increased F-18 FDG uptake in the anterior neck, chest wall, and upper abdomen. We suspected distant metastases of cervical lymph nodes, ribs, and peritoneum in gastric cancer. However, the transaxial images of F-18 FDG PET/CT showed abnormal F-18 FDG uptake in scalene muscles of anterior neck, intercostal muscles of chest wall, and diaphragm of upper abdomen. Patients with COPD use respiratory muscles extensively on the resting condition. These excessive physiologic use of respiratory muscles causes increased F-18 FDG uptake as a result of increased glucose metabolism. The F-18 FDG uptake in respiratory muscles of gastric cancer patient with COPD mimicked distant metastases in cervical lymph nodes, ribs, and peritoneum

Contraction-induced skeletal muscle FAT/CD36 trafficking and FA uptake is AMPK independent

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Jeppesen, J.; Albers, P. H.; Rose, A. J.; Birk, J. B.; Schjerling, P.; Dzamko, N.; Steinberg, G. R.; Kiens, B.

2011-01-01

The aim of this study was to investigate the molecular mechanisms regulating FA translocase CD36 (FAT/CD36) translocation and FA uptake in skeletal muscle during contractions. In one model, wild-type (WT) and AMP-dependent protein kinase kinase dead (AMPK KD) mice were exercised or extensor digitorum longus (EDL) and soleus (SOL) muscles were contracted, ex vivo. In separate studies, FAT/CD36 translocation and FA uptake in response to muscle contractions were investigated in the perfused rat hindlimb. Exercise induced a similar increase in skeletal muscle cell surface membrane FAT/CD36 content in WT (+34%) and AMPK KD (+37%) mice. In contrast, 5-aminoimidazole-4-carboxamide ribonucleoside only induced an increase in cell surface FAT/CD36 content in WT (+29%) mice. Furthermore, in the perfused rat hindlimb, muscle contraction induced a rapid (1 min, +15%) and sustained (10 min, +24%) FAT/CD36 relocation to cell surface membranes. The increase in cell surface FAT/CD36 protein content with muscle contractions was associated with increased FA uptake, both in EDL and SOL muscle from WT and AMPK KD mice and in the perfused rat hindlimb. This suggests that AMPK is not essential in regulation of FAT/CD36 translocation and FA uptake in skeletal muscle during contractions. However, AMPK could be important in regulation of FAT/CD36 distribution in other physiological situations. PMID:21297178

Intracellular uptake and degradation of extracellular tracers in mouse skeletal muscle in vitro: the effect of denervation

International Nuclear Information System (INIS)

Libelius, R.; Lundquist, I.; Templeton, W.; Thesleff, S.

1978-01-01

Innervated and chronically denervated mouse skeletal muscles have been incubated under various conditions in a Ringer solution containing one of the three macromolecules [ 3 H] α-neurotoxin, [ 3 H]inulin and horseradish peroxidase. Following extensive wash-out for 4 h of the extracellular compartment, the amount of each macromolecule retained intracellularly was obtained. Intracellular uptake of a [ 3 H]monoacetylated α-neurotoxin in vitro at 37 C was found to be increased in denervated mouse extensor digitorum longus muscles compared to innervated control muscles. Similarly, the uptake in vitro at 37 C of [ 3 H] inulin and horseradish peroxidase was also increased in denervated muscles. At 4 C the uptake of [ 3 H]inulin and horseradish peroxidase was markedly reduced. Protamine was found to stimulate the uptake of [ 3 H]inulin at 37 C, but not at 4 C. Reduction in specific activity by addition of 50-fold excess of unlabelled inulin failed to affect the uptake of [ 3 H]inulin suggesting that this uptake process obeyed bulk kinetics. Furthermore, the endocytized [ 3 H]inulin was found to be strongly retained in the muscles since prolonged washing or addition of unlabelled inulin to the washing solution did not reduce the uptake. Characterization of [ 3 H]inulin taken up by the muscles was performed by gel chromatography on Sephadex G-25. Using a purified [ 3 H]inulin solution it was observed that about 45% of the total radioactivity remaining in the muscles was eluted as [ 3 H]inulin. Additional radioactivity consisted of lower molecular weight compounds. These degradation products of [ 3 H]inulin were only present in the muscle homogenate and were not detected in the incubation solution. The results suggest that intracellular uptake of different macromolecules by endocytosis in skeletal muscles increases following denervation, and that following uptake, degradation of the endocytized material may occur. (author)

Mammalian target of rapamycin complex 2 regulates muscle glucose uptake during exercise in mice

DEFF Research Database (Denmark)

Kleinert, Maximilian; Parker, Benjamin L; Fritzen, Andreas Mæchel

2017-01-01

Exercise increases glucose uptake into insulin-resistant muscle. Thus, elucidating the exercise signalling network in muscle may uncover new therapeutic targets. mTORC2, a regulator of insulin-controlled glucose uptake, has been reported to interact with Rac1, which plays a role in exercise-induc...

Low density lipoprotein uptake by an endothelial-smooth muscle cell bilayer

International Nuclear Information System (INIS)

Alexander, J.J.; Miguel, R.; Graham, D.

1991-01-01

To study the interaction of endothelial and smooth muscle cells, and the means by which such interaction may affect lipid permeability of the arterial wall, cell bilayers were established by use of a transwell culture system. After confluent growth of both cell types had been achieved, iodine 125 bound to low-density lipoprotein (10 ng protein/ml) was added to the media of the upper well. After a 3-hour incubation period, the iodine 125-bound low-density lipoprotein content of the upper and lower media demonstrated an impedance to lipoprotein movement across the endothelial cell monolayer as compared to the bare porous polycarbonate filter of the transwell (p less than 10(-6)). The presence of smooth muscle cells in the bottom well significantly enhanced the permeability of the endothelial cell layer (p less than 10(-60)). This effect remained unchanged over a 9-day time course. Membrane binding and cellular uptake of low-density lipoprotein by endothelial cells was not altered by smooth muscle cells, indicating that this change in permeability could not be easily attributed to changes in receptor-mediated transport or transcytosis. Membrane binding (p less than 0.02) and cellular uptake (p less than 10(-6)) of low-density lipoprotein by smooth muscle cells in the bilayer, when adjusted for counts available in the smooth muscle cell media, were both reduced in the early incubation period as compared to isolated smooth muscle cells. The disproportionate reduction in uptake as compared to binding would suggest that this was not entirely a receptor-dependent process

111In antimyosin uptake in skeletal muscle: case report and literature review

International Nuclear Information System (INIS)

Alberini, J.L.; Bourguet, P.

1999-01-01

We report an observation of skeletal muscle uptake on antimyosin imaging. Aim of this imaging was to identify recent myocardial infarction in a patient resuscitated after cardio-version. Planar anterior and Left Anterior Oblique (45 deg. and 70 deg.) views centered on the thorax were performed 48 hours after injection of In-111 antimyosin. This uptake could be explained by a muscle necrosis, induced by the electroshock. Similar cases were reported with Tc-99m pyrophosphate. It must be remind on one hand the importance to perform several incidences for planar images and SPET and on the other hand the potential utility of antimyosin antibody imaging in skeletal muscle disorders. (authors)

Intracellular uptake and degradation of extracellular tracers in mouse skeletal muscle in vitro: the effect of denervation

Energy Technology Data Exchange (ETDEWEB)

Libelius, R; Lundquist, I; Templeton, W; Thesleff, S [Lund Univ. (Sweden)

1978-01-01

Innervated and chronically denervated mouse skeletal muscles have been incubated under various conditions in a Ringer solution containing one of the three macromolecules (/sup 3/H) ..cap alpha..-neurotoxin, (/sup 3/H)inulin and horseradish peroxidase. Following extensive wash-out for 4 h of the extracellular compartment, the amount of each macromolecule retained intracellularly was obtained. Intracellular uptake of a (/sup 3/H)monoacetylated ..cap alpha..-neurotoxin in vitro at 37 C was found to be increased in denervated mouse extensor digitorum longus muscles compared to innervated control muscles. Similarly, the uptake in vitro at 37 C of (/sup 3/H) inulin and horseradish peroxidase was also increased in denervated muscles. At 4 C the uptake of (/sup 3/H)inulin and horseradish peroxidase was markedly reduced. Protamine was found to stimulate the uptake of (/sup 3/H)inulin at 37 C, but not at 4 C. Reduction in specific activity by addition of 50-fold excess of unlabelled inulin failed to affect the uptake of (/sup 3/H)inulin suggesting that this uptake process obeyed bulk kinetics. Furthermore, the endocytized (/sup 3/H)inulin was found to be strongly retained in the muscles since prolonged washing or addition of unlabelled inulin to the washing solution did not reduce the uptake. Characterization of (/sup 3/H)inulin taken up by the muscles was performed by gel chromatography on Sephadex G-25. Using a purified (/sup 3/H)inulin solution it was observed that about 45% of the total radioactivity remaining in the muscles was eluted as (/sup 3/H)inulin. Additional radioactivity consisted of lower molecular weight compounds. Degradation products of (/sup 3/H)inulin were only present in the muscle homogenate and were not detected in the incubation solution. Results suggest that intracellular uptake of different macromolecules by endocytosis in skeletal muscles increases following denervation, and that following uptake, degradation of the endocytized material may occur.

No effect of NOS inhibition on skeletal muscle glucose uptake during in situ hindlimb contraction in healthy and diabetic Sprague-Dawley rats.

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Hong, Yet Hoi; Betik, Andrew C; Premilovac, Dino; Dwyer, Renee M; Keske, Michelle A; Rattigan, Stephen; McConell, Glenn K

2015-05-15

Nitric oxide (NO) has been shown to be involved in skeletal muscle glucose uptake during contraction/exercise, especially in individuals with Type 2 diabetes (T2D). To examine the potential mechanisms, we examined the effect of local NO synthase (NOS) inhibition on muscle glucose uptake and muscle capillary blood flow during contraction in healthy and T2D rats. T2D was induced in Sprague-Dawley rats using a combined high-fat diet (23% fat wt/wt for 4 wk) and low-dose streptozotocin injections (35 mg/kg). Anesthetized animals had one hindlimb stimulated to contract in situ for 30 min (2 Hz, 0.1 ms, 35 V) with the contralateral hindlimb rested. After 10 min, the NOS inhibitor, N(G)-nitro-l-arginine methyl ester (l-NAME; 5 μM) or saline was continuously infused into the femoral artery of the contracting hindlimb until the end of contraction. Surprisingly, there was no increase in skeletal muscle NOS activity during contraction in either group. Local NOS inhibition had no effect on systemic blood pressure or muscle contraction force, but it did cause a significant attenuation of the increase in femoral artery blood flow in control and T2D rats. However, NOS inhibition did not attenuate the increase in muscle capillary recruitment during contraction in these rats. Muscle glucose uptake during contraction was significantly higher in T2D rats compared with controls but, unlike our previous findings in hooded Wistar rats, NOS inhibition had no effect on glucose uptake during contraction. In conclusion, NOS inhibition did not affect muscle glucose uptake during contraction in control or T2D Sprague-Dawley rats, and this may have been because there was no increase in NOS activity during contraction. Copyright © 2015 the American Physiological Society.

Rac1 governs exercise‐stimulated glucose uptake in skeletal muscle through regulation of GLUT4 translocation in mice

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Nielsen, Ida L.; Kleinert, Maximilian; Møller, Lisbeth L. V.; Ploug, Thorkil; Schjerling, Peter; Bilan, Philip J.; Klip, Amira; Jensen, Thomas E.; Richter, Erik A.

2016-01-01

Key point Exercise increases skeletal muscle energy turnover and one of the important substrates for the working muscle is glucose taken up from the blood.The GTPase Rac1 can be activated by muscle contraction and has been found to be necessary for insulin‐stimulated glucose uptake, although its role in exercise‐stimulated glucose uptake is unknown.We show that Rac1 regulates the translocation of the glucose transporter GLUT4 to the plasma membrane in skeletal muscle during exercise.We find that Rac1 knockout mice display significantly reduced glucose uptake in skeletal muscle during exercise. Abstract Exercise increases skeletal muscle energy turnover and one of the important substrates for the working muscle is glucose taken up from the blood. Despite extensive efforts, the signalling mechanisms vital for glucose uptake during exercise are not yet fully understood, although the GTPase Rac1 is a candidate molecule. The present study investigated the role of Rac1 in muscle glucose uptake and substrate utilization during treadmill exercise in mice in vivo. Exercise‐induced uptake of radiolabelled 2‐deoxyglucose at 65% of maximum running capacity was blocked in soleus muscle and decreased by 80% and 60% in gastrocnemius and tibialis anterior muscles, respectively, in muscle‐specific inducible Rac1 knockout (mKO) mice compared to wild‐type littermates. By developing an assay to quantify endogenous GLUT4 translocation, we observed that GLUT4 content at the sarcolemma in response to exercise was reduced in Rac1 mKO muscle. Our findings implicate Rac1 as a regulatory element critical for controlling glucose uptake during exercise via regulation of GLUT4 translocation. PMID:27061726

Exercise training induces similar elevations in the activity of oxoglutarate dehydrogenase and peak oxygen uptake in the human quadriceps muscle

DEFF Research Database (Denmark)

Blomstrand, Eva; Krustrup, Peter; Søndergaard, Hans

2011-01-01

During exercise involving a small muscle mass, peak oxygen uptake is thought to be limited by peripheral factors, such as the degree of oxygen extraction from the blood and/or mitochondrial oxidative capacity. Previously, the maximal activity of the Krebs cycle enzyme oxoglutarate dehydrogenase has...

Low blood flow at onset of moderate-intensity exercise does not limit muscle oxygen uptake

DEFF Research Database (Denmark)

Nyberg, Michael Permin; Mortensen, Stefan P; Saltin, Bengt

2010-01-01

The effect of low blood flow at onset of moderate-intensity exercise on the rate of rise in muscle oxygen uptake was examined. Seven male subjects performed a 3.5-min one-legged knee-extensor exercise bout (24 +/- 1 W, mean +/- SD) without (Con) and with (double blockade; DB) arterial infusion...... of inhibitors of nitric oxide synthase (N(G)-monomethyl-l-arginine) and cyclooxygenase (indomethacin) to inhibit the synthesis of nitric oxide and prostanoids, respectively. Leg blood flow and leg oxygen delivery throughout exercise was 25-50% lower (P ... +/- 12 vs. 262 +/- 39 ml/min). The present data demonstrate that muscle blood flow and oxygen delivery can be markedly reduced without affecting muscle oxygen uptake in the initial phase of moderate-intensity exercise, suggesting that blood flow does not limit muscle oxygen uptake at the onset...

Increased technetium uptake is not equivalent to muscle necrosis: scintigraphic, morphological and intramuscular pressure analyses of sore muscles after exercise

Science.gov (United States)

Crenshaw, A. G.; Friden, J.; Hargens, A. R.; Lang, G. H.; Thornell, L. E.

1993-01-01

A scintigraphic technique employing technetium pyrophosphate uptake was used to identify the area of skeletal muscle damage in the lower leg of four runners 24 h after an ultramarathon footrace (160 km). Most of the race had been run downhill which incorporated an extensive amount of eccentric work. Soreness was diffuse throughout the posterior region of the lower leg. In order to interpret what increased technetium uptake reflects and to express extreme endurance related damages, a biopsy was taken from the 3-D position of abnormal uptake. In addition, intramuscular pressures were determined in the deep posterior compartment. Scintigraphs revealed increased technetium pyrophosphate uptake in the medial portion of the gastrocnemius muscle. For 3698 fibres analysed, 33 fibres (1%) were necrotic, while a few other fibres were either atrophic or irregular shaped. A cluster of necrotic fibres occurred at the fascicular periphery for one subject and fibre type grouping occurred for another. Ultrastructural analysis revealed Z-line streaming near many capillaries and variously altered subsarcolemmal mitochondria including some with paracrystalline inclusions. The majority of the capillaries included thickened and irregular shaped endothelial cells. Intramuscular pressures of the deep posterior compartment were slightly elevated (12-15 mmHg) for three of the four subjects. Increased technetium uptake following extreme endurance running does not just reflect muscle necrosis but also subtle fibre abnormalities. Collectively, these pathological findings are attributed to relative ischaemia occurring during the race and during pre-race training, whereas, intramuscular pressure elevations associated with muscle soreness are attributed to mechanical stress caused by extensive eccentric work during the race.

Glucose-induced insulin resistance of skeletal-muscle glucose transport and uptake

DEFF Research Database (Denmark)

Richter, Erik; Hansen, B F; Hansen, S A

1988-01-01

in the presence of glucose and insulin. The data indicate that exposure to a moderately increased glucose concentration (12 mM) leads to rapidly developing resistance of skeletal-muscle glucose transport and uptake to maximal insulin stimulation. The effect of glucose is enhanced by simultaneous insulin exposure......, whereas exposure for 5 h to insulin itself does not cause measurable resistance to maximal insulin stimulation.......The ability of glucose and insulin to modify insulin-stimulated glucose transport and uptake was investigated in perfused skeletal muscle. Here we report that perfusion of isolated rat hindlimbs for 5 h with 12 mM-glucose and 20,000 microunits of insulin/ml leads to marked, rapidly developing...

Glucose uptake and transport in contracting, perfused rat muscle with different pre-contraction glycogen concentrations

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Hespel, P; Richter, Erik

1990-01-01

1. Glucose uptake and transport, muscle glycogen, free glucose and glucose-6-phosphate concentrations were studied in perfused resting and contracting rat skeletal muscle with different pre-contraction glycogen concentrations. Rats were pre-conditioned by a combination of swimming exercise and diet......, resulting in either low (glycogen-depleted rats), normal (control rats) or high (supercompensated rats) muscle glycogen concentrations at the time their hindlimbs were perfused. 2. Compared with control rats, pre-contraction muscle glycogen concentration was approximately 40% lower in glycogen-depleted rats......, whereas it was 40% higher in supercompensated rats. Muscle glycogen break-down correlated positively (r = 0.76; P less than 0.001) with pre-contraction muscle glycogen concentration. 3. Glucose uptake during contractions was approximately 50% higher in glycogen-depleted hindquarters than in control...

Two weeks of metformin treatment induces AMPK dependent enhancement of insulin-stimulated glucose uptake in mouse soleus muscle

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Kristensen, Jonas Møller; Treebak, Jonas Thue; Schjerling, Peter

2014-01-01

signaling. Methods: Oral doses of metformin or saline treatment were given muscle-specific kinase α2 dead AMPK mice (KD) and wild type (WT) littermates either once or chronically for 2 weeks. Soleus and Extensor Digitorum Longus (EDL) muscles were used for measurements of glucose transport and Western blot......Background: Metformin-induced activation of AMPK has been associated with enhanced glucose uptake in skeletal muscle but so far no direct causality has been examined. We hypothesized that an effect of in vivo metformin treatment on glucose uptake in mouse skeletal muscles is dependent upon AMPK...... analyzes. Results: Chronic treatment with metformin enhanced insulin-stimulated glucose uptake in soleus muscles of WT (45%, P...

Insulin-stimulated glucose uptake in healthy and insulin-resistant skeletal muscle

DEFF Research Database (Denmark)

Deshmukh, Atul S

2016-01-01

transporter protein 4 (GLUT4) to the plasma membrane which leads to facilitated diffusion of glucose into the cell. Understanding the precise signaling events guiding insulin-stimulated glucose uptake is pivotal, because impairment in these signaling events leads to development of insulin resistance and type...... 2 diabetes. This review summarizes current understanding of insulin signaling pathways mediating glucose uptake in healthy and insulin-resistant skeletal muscle....

Ammonia uptake in inactive muscles during exercise in humans

DEFF Research Database (Denmark)

Bangsbo, Jens; Kiens, Bente; Richter, Erik

1996-01-01

The present study examined NH3 (ammonia and ammonium) uptake in resting leg muscle. Six male subjects performed intermittent arm exercise at various intensities in two separate 32-min periods (part I and part II) and in one subsequent 20-min period in which one-legged exercise was also performed ...

Two weeks of metformin treatment induces AMPK-dependent enhancement of insulin-stimulated glucose uptake in mouse soleus muscle

Science.gov (United States)

Kristensen, Jonas Møller; Treebak, Jonas T.; Schjerling, Peter; Goodyear, Laurie

2014-01-01

Metformin-induced activation of the 5′-AMP-activated protein kinase (AMPK) has been associated with enhanced glucose uptake in skeletal muscle, but so far no direct causality has been examined. We hypothesized that an effect of in vivo metformin treatment on glucose uptake in mouse skeletal muscles is dependent on AMPK signaling. Oral doses of metformin or saline treatment were given to muscle-specific kinase dead (KD) AMPKα2 mice and wild-type (WT) littermates either once or chronically for 2 wk. Soleus and extensor digitorum longus muscles were used for measurements of glucose transport and Western blot analyses. Chronic treatment with metformin enhanced insulin-stimulated glucose uptake in soleus muscles of WT (∼45%, P metformin treatment. Insulin signaling at the level of Akt and TBC1D4 protein expression as well as Akt Thr308/Ser473 and TBC1D4 Thr642/Ser711 phosphorylation were not changed by metformin treatment. Also, protein expressions of Rab4, GLUT4, and hexokinase II were unaltered after treatment. The acute metformin treatment did not affect glucose uptake in muscle of either of the genotypes. In conclusion, we provide novel evidence for a role of AMPK in potentiating the effect of insulin on glucose uptake in soleus muscle in response to chronic metformin treatment. PMID:24644243

Influence of exercise intensity on skeletal muscle blood flow, O2 extraction and O2 uptake on-kinetics

DEFF Research Database (Denmark)

Jones, Andrew M; Krustrup, Peter; Wilkerson, Daryl P

2012-01-01

Key points Following the start of low-intensity exercise in healthy humans, it has been established that the kinetics of muscle O(2) delivery is faster than, and does not limit, the kinetics of muscle O(2) uptake. Direct data are lacking, however, on the question of whether O(2) delivery might...... limit O(2) uptake kinetics during high-intensity exercise. In this study, we made frequent measurements of muscle blood flow, arterial-to-venous O(2) difference (a- difference) and O(2) uptake following the onset of multiple transitions of both low-intensity and high-intensity knee-extension exercise...... in the same subjects. We show that although blood flow kinetics is slower for high-intensity compared with low-intensity exercise, this does not result in slower O(2) uptake kinetics. These results indicate that muscle O(2) delivery does not limit O(2) uptake during knee-extension exercise in healthy humans....

18F-fluorodeoxyglucose and PET/CT for noninvasive study of exercise-induced glucose uptake in rat skeletal muscle and tendon

International Nuclear Information System (INIS)

Skovgaard, Dorthe; Kjaer, Michael; El-Ali, Henrik; Kjaer, Andreas

2009-01-01

To investigate exercise-related glucose uptake in rat muscle and tendon using PET/CT and to study possible explanatory changes in gene expression for the glucose transporters (GLUT1 and GLUT4). The sciatic nerve in eight Wistar rats was subjected to electrostimulation to cause unilateral isometric contractions of the calf muscle. 18 F-Fluorodeoxyglucose was administered and a PET/CT scan of the hindlimbs was performed. SUVs were calculated in both Achilles tendons and the triceps surae muscles. To exclude a spill-over effect the tendons and muscles from an ex vivo group of eight rats were cut out and scanned separately (distance≥1 cm). Muscle contractions increased glucose uptake approximately sevenfold in muscles (p<0.001) and 36% in tendons (p<0.01). The ex vivo group confirmed the increase in glucose uptake in intact animals. GLUT1 and GLUT4 were expressed in both skeletal muscle and tendon, but no changes in mRNA levels could be detected. PET/CT can be used for studying glucose uptake in rat muscle and tendon in relation to muscle contractions; however, the increased uptake of glucose was not explained by changes in gene expression of GLUT1 and GLUT4. (orig.)

Wortmannin inhibits both insulin- and contraction-stimulated glucose uptake and transport in rat skeletal muscle

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Wojtaszewski, Jørgen; Hansen, B F; Ursø, Birgitte

1996-01-01

The role of phosphatidylinositol (PI) 3-kinase for insulin- and contraction-stimulated muscle glucose transport was investigated in rat skeletal muscle perfused with a cell-free perfusate. The insulin receptor substrate-1-associated PI 3-kinase activity was increased sixfold upon insulin...... stimulation but was unaffected by contractions. In addition, the insulin-stimulated PI 3-kinase activity and muscle glucose uptake and transport in individual muscles were dose-dependently inhibited by wortmannin with one-half maximal inhibition values of approximately 10 nM and total inhibition at 1 micro......M. This concentration of wortmannin also decreased the contraction-stimulated glucose transport and uptake by approximately 30-70% without confounding effects on contractility or on muscle ATP and phosphocreatine concentrations. At higher concentrations (3 and 10 microM), wortmannin completely blocked the contraction...

Rac1 and AMPK account for the majority of muscle glucose uptake stimulated by ex vivo contraction but not in vivo exercise

DEFF Research Database (Denmark)

Sylow, Lykke; Møller, Lisbeth Liliendal Valbjørn; Kleinert, Maximilian

2017-01-01

Exercise bypasses insulin resistance to increase glucose uptake in skeletal muscle and therefore represents an important alternative to stimulate glucose uptake in insulin resistant muscle. Both Rac1 and AMPK have been shown to partly regulate contraction-stimulated muscle glucose uptake but whet...

Leukemia inhibitory factor increases glucose uptake in mouse skeletal muscle

DEFF Research Database (Denmark)

Brandt, Nina; O'Neill, Hayley M; Kleinert, Maximilian

2015-01-01

INTRODUCTION: Members of the interleukin-6 (IL-6) family, IL-6 and ciliary neurotrophic factor (CNTF) have been shown to increase glucose uptake and fatty acid oxidation in skeletal muscle. However, the metabolic effects of another family member, leukemia inhibitory factor (LIF), are not well...

Exercise and Type 2 Diabetes: Molecular Mechanisms Regulating Glucose Uptake in Skeletal Muscle

Science.gov (United States)

Stanford, Kristin I.; Goodyear, Laurie J.

2014-01-01

Exercise is a well-established tool to prevent and combat type 2 diabetes. Exercise improves whole body metabolic health in people with type 2 diabetes, and adaptations to skeletal muscle are essential for this improvement. An acute bout of exercise increases skeletal muscle glucose uptake, while chronic exercise training improves mitochondrial…

Knockout of the predominant conventional PKC isoform, PKCalpha, in mouse skeletal muscle does not affect contraction-stimulated glucose uptake

DEFF Research Database (Denmark)

Jensen, Thomas E; Maarbjerg, Stine J; Rose, Adam J

2009-01-01

Conventional (c) protein kinase C (PKC) activity has been shown to increase with skeletal muscle contraction, and numerous studies using primarily pharmacological inhibitors have implicated cPKCs in contraction-stimulated glucose uptake. Here, to confirm that cPKC activity is required for contrac...... working on other parts of contraction-induced signaling or the remaining cPKC isoforms are sufficient for stimulating glucose uptake during contractions.......Conventional (c) protein kinase C (PKC) activity has been shown to increase with skeletal muscle contraction, and numerous studies using primarily pharmacological inhibitors have implicated cPKCs in contraction-stimulated glucose uptake. Here, to confirm that cPKC activity is required...... for contraction-stimulated glucose uptake in mouse muscles, contraction-stimulated glucose uptake ex vivo was first evaluated in the presence of three commonly used cPKC inhibitors (calphostin C, Gö-6976, and Gö-6983) in incubated mouse soleus and extensor digitorum longus (EDL) muscles. All potently inhibited...

Myo-inositol inhibits intestinal glucose absorption and promotes muscle glucose uptake: a dual approach study.

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Chukwuma, Chika Ifeanyi; Ibrahim, Mohammed Auwal; Islam, Md Shahidul

2016-12-01

The present study investigated the effects of myo-inositol on muscle glucose uptake and intestinal glucose absorption ex vivo as well as in normal and type 2 diabetes model of rats. In ex vivo study, both intestinal glucose absorption and muscle glucose uptake were studied in isolated rat jejunum and psoas muscle respectively in the presence of increasing concentrations (2.5 % to 20 %) of myo-inositol. In the in vivo study, the effect of a single bolus dose (1 g/kg bw) of oral myo-inositol on intestinal glucose absorption, blood glucose, gastric emptying and digesta transit was investigated in normal and type 2 diabetic rats after 1 h of co-administration with 2 g/kg bw glucose, when phenol red was used as a recovery marker. Myo-inositol inhibited intestinal glucose absorption (IC 50  = 28.23 ± 6.01 %) and increased muscle glucose uptake, with (GU 50  = 2.68 ± 0.75 %) or without (GU 50  = 8.61 ± 0.55 %) insulin. Additionally, oral myo-inositol not only inhibited duodenal glucose absorption and reduced blood glucose increase, but also delayed gastric emptying and accelerated digesta transit in both normal and diabetic animals. Results of this study suggest that dietary myo-inositol inhibits intestinal glucose absorption both in ex vivo and in normal or diabetic rats and also promotes muscle glucose uptake in ex vivo condition. Hence, myo-inositol may be further investigated as a possible anti-hyperglycaemic dietary supplement for diabetic foods and food products.

Contraction-induced skeletal muscle FAT/CD36 trafficking and FA uptake is AMPK independent

DEFF Research Database (Denmark)

Jeppesen, Jacob; Albers, Peter Hjorth; Rose, Adam John

2011-01-01

The aim of this study was to investigate the molecular mechanisms regulating FAT/CD36 translocation and fatty acid uptake in skeletal muscle during contractions. In one model, WT and AMPK KD mice were exercised or EDL and SOL muscles were contracted, ex vivo. In separate studies, FAT/CD36 translo...

The significance of alteration 2-[fluorine-18]fluoro-2-deoxy-(D)-glucose uptake in the liver and skeletal muscles of patients with hyperthyroidism.

Science.gov (United States)

Chen, Yen-Kung; Chen, Yen-Ling; Tsui, Chih-Cheng; Wang, Su-Chen; Cheng, Ru-Hwa

2013-10-01

Hyperthyroidism leads to an enhanced demand for glucose. The hypothesis of the study is that 2-[fluorine-18]fluoro-2-deoxy-d-glucose (FDG) positron emission tomography (PET) can demonstrate the alteration of systemic glucose metabolism in hyperthyroidism patients by measuring the FDG standard uptake value (SUV) in liver and skeletal muscle. Forty-eight active hyperthyroidism patients and 30 control participants were recruited for the study. The intensity of FDG uptake in the liver and thigh muscles was graded subjectively, comprising three groups: group I, higher FDG uptake in the liver; group II, equal FDG uptake in the liver and muscles; and group III, higher FDG uptake in the muscles. Ten subjects with FDG PET scans at hyperthyroid and euthyroid status were analyzed. Serum levels of thyroxine (T4) and triiodothyronine (T3) correlated to the SUVs of the liver and muscles. Forty-one patients (41/48, 85.4%) showed symmetrically increased FDG uptake in the muscles (22 in group I, 9 in group II, and 17 in group III). Group I patients were significantly older than group II (P = .02) and group III (P = .001) patients. The correlation coefficient between the serum T3, T4, and SUV levels in the muscles was significant (r = 0.47-0.77, P hyperthyroid and euthyroid states. In the 30 control subjects, there was normal physiological FDG uptake in the liver and muscles. In PET scans showing a pattern of decreased liver and increased skeletal muscle FDG uptake in hyperthyroidism patients, this change of FDG distribution is correspondence to the severity of hyperthyroidism status. Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.

A Patient with Psoriatic Arthritis Imaged with FDG PET/CT Demonstrated an Unusual Imaging Pattern with Muscle and Fascia Involvement: A Case Report

Energy Technology Data Exchange (ETDEWEB)

Bains, Sukharn; Khan, Sana; Aparici, Carina Mari [Univ. of California, San Francisco (United States); Win, Aung Zaw; Reimert, Matthew [San Fracisco Veterans Affairs Medical Center, San Francisco (United States)

2012-06-15

We describe the case of a patient with known history of psoriasis that presented with 1 year of unexplained fever, muscle weakness and marked weight loss, suspicious for B symptoms of a malignant origin. [{sup 18}F]-Fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET/CT) scans demonstrated an unusual serpiginous pattern of uptake in the fascia and muscles as well as lymph node activity. Multiple histological samples, including a final PET-probe guided lymph node surgical resection, excluded malignancy and confirmed the diagnosis of reactive inflammatory changes, with a plausible diagnosis of autoimmune lymphoproliferative syndrome with associated lymphadenitis, fasciitis and myositis, possibly mediated by tumor necrosis factor (TNF) inhibitor. To our knowledge, there is no evidence of a previously reported FDG uptake pattern of fascia and muscle involvement in psoriatic arthritis.

Fiber type effects on contraction-stimulated glucose uptake and GLUT4 abundance in single fibers from rat skeletal muscle.

Science.gov (United States)

Castorena, Carlos M; Arias, Edward B; Sharma, Naveen; Bogan, Jonathan S; Cartee, Gregory D

2015-02-01

To fully understand skeletal muscle at the cellular level, it is essential to evaluate single muscle fibers. Accordingly, the major goals of this study were to determine if there are fiber type-related differences in single fibers from rat skeletal muscle for: 1) contraction-stimulated glucose uptake and/or 2) the abundance of GLUT4 and other metabolically relevant proteins. Paired epitrochlearis muscles isolated from Wistar rats were either electrically stimulated to contract (E-Stim) or remained resting (No E-Stim). Single fibers isolated from muscles incubated with 2-deoxy-d-[(3)H]glucose (2-DG) were used to determine fiber type [myosin heavy chain (MHC) isoform protein expression], 2-DG uptake, and abundance of metabolically relevant proteins, including the GLUT4 glucose transporter. E-Stim, relative to No E-Stim, fibers had greater (P contraction-stimulated glucose uptake. Copyright © 2015 the American Physiological Society.

Abnormalities of AMPK activation and glucose uptake in cultured skeletal muscle cells from individuals with chronic fatigue syndrome.

Directory of Open Access Journals (Sweden)

Audrey E Brown

Full Text Available Post exertional muscle fatigue is a key feature in Chronic Fatigue Syndrome (CFS. Abnormalities of skeletal muscle function have been identified in some but not all patients with CFS. To try to limit potential confounders that might contribute to this clinical heterogeneity, we developed a novel in vitro system that allows comparison of AMP kinase (AMPK activation and metabolic responses to exercise in cultured skeletal muscle cells from CFS patients and control subjects.Skeletal muscle cell cultures were established from 10 subjects with CFS and 7 age-matched controls, subjected to electrical pulse stimulation (EPS for up to 24h and examined for changes associated with exercise.In the basal state, CFS cultures showed increased myogenin expression but decreased IL6 secretion during differentiation compared with control cultures. Control cultures subjected to 16 h EPS showed a significant increase in both AMPK phosphorylation and glucose uptake compared with unstimulated cells. In contrast, CFS cultures showed no increase in AMPK phosphorylation or glucose uptake after 16 h EPS. However, glucose uptake remained responsive to insulin in the CFS cells pointing to an exercise-related defect. IL6 secretion in response to EPS was significantly reduced in CFS compared with control cultures at all time points measured.EPS is an effective model for eliciting muscle contraction and the metabolic changes associated with exercise in cultured skeletal muscle cells. We found four main differences in cultured skeletal muscle cells from subjects with CFS; increased myogenin expression in the basal state, impaired activation of AMPK, impaired stimulation of glucose uptake and diminished release of IL6. The retention of these differences in cultured muscle cells from CFS subjects points to a genetic/epigenetic mechanism, and provides a system to identify novel therapeutic targets.

Thyroid hormone uptake and T4 derived T3 formation in different skeletal muscle types of normal and hyperthyroid rats

International Nuclear Information System (INIS)

Hardeveld, C. van; Kassenaar, A.A.H.

1978-01-01

In this study hind-limb perfusion was used to investigate conversion of T 4 to T 3 in skeletal muscle tissue. For this purpose the rats were depleted of thyroid hormones by thyroid ablation with 0.75 mCi 131 I and were perfused 2 weeks later, when the skeletal muscle tissue consumed oxygen at a normal rate due to one subcutaneous dose of 10 μg T 3 /100 g b. w. 3 days before the perfusion experiments were started. T 4 * of high specific activity (> 2000 μCi/μg) was added to the perfusate. In the muscle (mixed type) a mean T 4 → T 3 conversion of 2% (range 0.5-3.9) was found after 120 min of perfusion. T 3 generation from T 4 in skeletal muscle did not correspond with T 3 muscle uptake. This observation makes a significant overestimation of T 3 by selective uptake of a small contamination of T 3 * in the T 4 * preparation highly improbable. In red muscle the T 4 and T 3 uptake was about 50 % higher than in white muscle. The observed Tetracsup(c) and T 3 sup(c) were significantly higher in red than in white muscle. The uptake of thyroid hormones by both muscle types was not changed in hyperthyroid rats. The Tetrac and T 3 formation from T 4 , however, was increased in red muscles of hyperthyroid rats. The results show that thyroid hormone metabolism can vary markedly depending upon the type of muscle studied and they present a basis for a better understanding of clinical and biochemical evidence for a different susceptibility of red and white muscle fibers to thyroid hormones. (Abbreviations: *= 125 I; **= 131 I; T 3 sup(c)=T 4 derived T 3 ; Tetracsup(c)=T 4 derived Tetrac) (author)

Neuromuscular blockade of slow twitch muscle fibres elevates muscle oxygen uptake and energy turnover during submaximal exercise in humans.

Science.gov (United States)

Krustrup, Peter; Secher, Niels H; Relu, Mihai U; Hellsten, Ylva; Söderlund, Karin; Bangsbo, Jens

2008-12-15

We tested the hypothesis that a greater activation of fast-twitch (FT) fibres during dynamic exercise leads to a higher muscle oxygen uptake (VO2 ) and energy turnover as well as a slower muscle on-kinetics. Subjects performed one-legged knee-extensor exercise for 10 min at an intensity of 30 W without (CON) and with (CUR) arterial injections of the non-depolarizing neuromuscular blocking agent cisatracurium. In CUR, creatine phosphate (CP) was unaltered in slow twitch (ST) fibres and decreased (P fibres, whereas in CON, CP decreased (P fibres, respectively. From 127 s of exercise, muscle VO2 was higher (P muscle VO2 response was slower (P muscle homogenate CP was lowered (P muscle lactate production was similar in CUR and CON (37.8 +/- 4.1 versus 35.2 +/- 6.2 mmol). Estimated total muscle ATP turnover was 19% higher (P fibres are less efficient than ST fibres in vivo at a contraction frequency of 1 Hz, and that the muscle VO2 kinetics is slowed by FT fibre activation.

Neuromuscular blockade of slow twitch muscle fibres elevates muscle oxygen uptake and energy turnover during submaximal exercise in humans

DEFF Research Database (Denmark)

Krustrup, Peter; Secher, Niels; Relu, Mihai U.

2008-01-01

We tested the hypothesis that a greater activation of fast-twitch (FT) fibres during dynamic exercise leads to a higher muscle oxygen uptake (VO2 ) and energy turnover as well as a slower muscle on-kinetics. Subjects performed one-legged knee-extensor exercise for 10 min at an intensity of 30 W...... without (CON) and with (CUR) arterial injections of the non-depolarizing neuromuscular blocking agent cisatracurium. In CUR, creatine phosphate (CP) was unaltered in slow twitch (ST) fibres and decreased (P fibres, whereas in CON, CP decreased (P ... at a contraction frequency of 1 Hz, and that the muscle VO2 kinetics is slowed by FT fibre activation....

Involvement of atypical protein kinase C in the regulation of cardiac glucose and long-chain fatty acid uptake

Directory of Open Access Journals (Sweden)

Daphna D.J. Habets

2012-09-01

Full Text Available Aim: The signaling pathways involved in the regulation of cardiac GLUT4 translocation/glucose uptake and CD36 translocation/ long-chain fatty acid uptake are not fully understood. We compared in heart/muscle-specific PKC-λ knockout mice the roles of atypical PKCs (PKC-ζ and PKC-λ in regulating cardiac glucose and fatty acid uptake. Results: Neither insulin-stimulated nor AMPK-mediated glucose and fatty acid uptake were inhibited upon genetic PKC-λ ablation in cardiomyocytes. In contrast, myristoylated PKC-ζ pseudosubstrate inhibited both insulin-stimulated and AMPK-mediated glucose and fatty acid uptake by >80% in both wild-type and PKC-λ-knockout cardiomyocytes. In PKC-λ knockout cardiomyocytes, PKC-ζ is the sole remaining atypical PKC isoform, and its expression level is not different from wild-type cardiomyocytes, in which it contributes to 29% and 17% of total atypical PKC expression and phosphorylation, respectively. Conclusion: Taken together, atypical PKCs are necessary for insulin-stimulated and AMPK-mediated glucose uptake into the heart, as well as for insulin-stimulated and AMPK-mediated fatty acid uptake. However, the residual PKC-ζ activity in PKC-λ-knockout cardiomyocytes is sufficient to allow optimal stimulation of glucose and fatty acid uptake, indicating that atypical PKCs are necessary but not rate-limiting in the regulation of cardiac substrate uptake and that PKC-λ and PKC-ζ have interchangeable functions in these processes.

The effect of dynamic knee-extension exercise on patellar tendon and quadriceps femoris muscle glucose uptake in humans studied by positron emission tomography

DEFF Research Database (Denmark)

Kalliokoski, Kari K; Langberg, Henning; Ryberg, Ann Kathrine

2005-01-01

Both tendon and peritendinous tissue show evidence of metabolic activity, but the effect of acute exercise on substrate turnover is unknown. We therefore examined the influence of acute exercise on glucose uptake in the patellar and quadriceps tendons during dynamic exercise in humans. Glucose...... that tendon glucose uptake is increased during exercise. However, the increase in tendon glucose uptake is less pronounced than in muscle and the increases are uncorrelated. Thus tendon glucose uptake is likely to be regulated by mechanisms independently of those regulating skeletal muscle glucose uptake....... uptake was measured in five healthy men in the patellar and quadriceps tendons and the quadriceps femoris muscle at rest and during dynamic knee-extension exercise (25 W) using positron emission tomography and [18F]-2-fluoro-2-deoxy-D-glucose ([18F]FDG). Glucose uptake index was calculated by dividing...

Nitric oxide and prostaglandins influence local skeletal muscle blood flow during exercise in humans: coupling between local substrate uptake and blood flow

DEFF Research Database (Denmark)

Kalliokoski, Kari K; Langberg, Henning; Ryberg, Ann Kathrine

2006-01-01

-legged dynamic knee-extension exercise. Local blockade was produced by infusing nitro-L-arginine methyl ester and indomethacin directly in the muscle via a microdialysis catheter. Blood flow and glucose uptake were measured in the region of blockade and in two additional regions of vastus lateralis muscle 1......Synergic action of nitric oxide (NO) and prostaglandins (PG) in the regulation of muscle blood flow during exercise has been demonstrated. In the present study, we investigated whether these vasodilators also regulate local blood flow, flow heterogeneity, and glucose uptake within the exercising...... skeletal muscle. Skeletal muscle blood flow was measured in seven healthy young men using near-infrared spectroscopy and indocyanine green and muscle glucose uptake using positron emission tomography and 2-fluoro-2-deoxy-D-[(18)F]glucose without and with local blockade of NO and PG at rest and during one...

Down-regulation of lipoprotein lipase increases glucose uptake in L6 muscle cells

Energy Technology Data Exchange (ETDEWEB)

Lopez, Veronica; Saraff, Kumuda [Department of Chemistry and Biochemistry, California State University Northridge, Northridge, CA 91330-8262 (United States); Medh, Jheem D., E-mail: jheem.medh@csun.edu [Department of Chemistry and Biochemistry, California State University Northridge, Northridge, CA 91330-8262 (United States)

2009-11-06

Thiazolidinediones (TZDs) are synthetic hypoglycemic agents used to treat type 2 diabetes. TZDs target the peroxisome proliferator activated receptor-gamma (PPAR-{gamma}) and improve systemic insulin sensitivity. The contributions of specific tissues to TZD action, or the downstream effects of PPAR-{gamma} activation, are not very clear. We have used a rat skeletal muscle cell line (L6 cells) to demonstrate that TZDs directly target PPAR-{gamma} in muscle cells. TZD treatment resulted in a significant repression of lipoprotein lipase (LPL) expression in L6 cells. This repression correlated with an increase in glucose uptake. Down-regulation of LPL message and protein levels using siRNA resulted in a similar increase in insulin-dependent glucose uptake. Thus, LPL down-regulation improved insulin sensitivity independent of TZDs. This finding provides a novel method for the management of insulin resistance.

A study of muscle involvement in scrub typhus.

Science.gov (United States)

Kalita, Jayantee; Misra, Usha K; Mani, Vinita E; Mahadevan, Anita; Shankar, Susrala K

2015-01-15

Patients with scrub typhus often complain of myalgia, but a comprehensive study on muscle dysfunction is lacking. We therefore report the clinical, electromyographic and muscle biopsy findings in patients with scrub typhus. Consecutive patients with scrub typhus were included, and their clinical and laboratory findings were noted. The patients with myalgia or weakness and elevated serum creatine kinase (CK) were considered to have muscle involvement. Electromyography (EMG) and muscle biopsy were done in some patients. Patients were treated with doxycycline 200mg daily for 7 days, and their clinical and biochemical outcome on discharge and one month were evaluated. 13 out of 33 (39.4%) patients had muscle involvement and their CK levels ranged between 287 and 3166 (859 ± 829) U/L. EMG revealed short duration polyphasic potentials, and muscle histopathology revealed evidence of vasculitis. There were significant correlations between severity of weakness and CK levels (r = -0.6; p scrub typhus. Although muscle histopathology showed evidence of vasculitis, patients responded to doxycycline. Copyright © 2014 Elsevier B.V. All rights reserved.

Rac1 and AMPK Account for the Majority of Muscle Glucose Uptake Stimulated by Ex Vivo Contraction but Not In Vivo Exercise.

Science.gov (United States)

Sylow, Lykke; Møller, Lisbeth L V; Kleinert, Maximilian; D'Hulst, Gommaar; De Groote, Estelle; Schjerling, Peter; Steinberg, Gregory R; Jensen, Thomas E; Richter, Erik A

2017-06-01

Exercise bypasses insulin resistance to increase glucose uptake in skeletal muscle and therefore represents an important alternative to stimulate glucose uptake in insulin-resistant muscle. Both Rac1 and AMPK have been shown to partly regulate contraction-stimulated muscle glucose uptake, but whether those two signaling pathways jointly account for the entire signal to glucose transport is unknown. We therefore studied the ability of contraction and exercise to stimulate glucose transport in isolated muscles with AMPK loss of function combined with either pharmacological inhibition or genetic deletion of Rac1.Muscle-specific knockout (mKO) of Rac1, a kinase-dead α2 AMPK (α2KD), and double knockout (KO) of β1 and β2 AMPK subunits (β1β2 KO) each partially decreased contraction-stimulated glucose transport in mouse soleus and extensor digitorum longus (EDL) muscle. Interestingly, when pharmacological Rac1 inhibition was combined with either AMPK β1β2 KO or α2KD, contraction-stimulated glucose transport was almost completely inhibited. Importantly, α2KD+Rac1 mKO double-transgenic mice also displayed severely impaired contraction-stimulated glucose transport, whereas exercise-stimulated glucose uptake in vivo was only partially reduced by Rac1 mKO with no additive effect of α2KD. It is concluded that Rac1 and AMPK together account for almost the entire ex vivo contraction response in muscle glucose transport, whereas only Rac1, but not α2 AMPK, regulates muscle glucose uptake during submaximal exercise in vivo. © 2017 by the American Diabetes Association.

Increased uptake of technetium-99m methylene diphosphonate in muscles in the course of polymyositis

International Nuclear Information System (INIS)

Niemir, Z.; Oleksa, R.; Czepczynski, R.; Sowinski, J.

2005-01-01

A case of a woman aged 46 years with signs of rhabdomyolysis and acute renal failure is presented. Coxsackie serum test was positive. Increased uptake of Technetium-99m methylene diphosphonate ( 99mT c-MDP) by muscles of thighs and calves was observed. After 1 year no increased accumulation of radiotracer in the muscles was found

Effect of sepsis on calcium uptake and content in skeletal muscle and regulation in vitro by calcium of total and myofibrillar protein breakdown in control and septic muscle: Results from a preliminary study

International Nuclear Information System (INIS)

Benson, D.W.; Hasselgren, P.O.; Hiyama, D.T.; James, J.H.; Li, S.; Rigel, D.F.; Fischer, J.E.

1989-01-01

Because high calcium concentration in vitro stimulates muscle proteolysis, calcium has been implicated in the pathogenesis of increased muscle breakdown in different catabolic conditions. Protein breakdown in skeletal muscle is increased during sepsis, but the effect of sepsis on muscle calcium uptake and content is not known. In this study the influence of sepsis, induced in rats by cecal ligation and puncture, on muscle calcium uptake and content was studied. Sixteen hours after cecal ligation and puncture or sham operation, calcium content of the extensor digitorum longus (EDL) and soleus (SOL) muscles was determined with an atomic absorption spectrometer. Calcium uptake was measured in intact SOL muscles incubated in the presence of calcium 45 (45Ca) for between 1 and 120 minutes. Total and myofibrillar protein breakdown was determined in SOL muscles, incubated in the presence of different calcium concentrations (0; 2.5; 5.0 mmol/L), and measured as release into the incubation medium of tyrosine and 3-methylhistidine (3-MH), respectively. Calcium content was increased by 51% (p less than 0.001) during sepsis in SOL and by 10% (p less than 0.05) in EDL muscle. There was no difference in 45Ca uptake between control and septic muscles during the early phase (1 to 5 minutes) of incubation. During more extended incubation (30 to 120 minutes), muscles from septic rats took up significantly more 45Ca than control muscles (p less than 0.05). Tyrosine release by incubated SOL muscles from control and septic rats was increased when calcium was added to the incubation medium, and at a calcium concentration of 2.5 mmol/L, the increase in tyrosine release was greater in septic than in control muscle. Addition of calcium to the incubation medium did not affect 3-MH release in control or septic muscle

FDG-PET/CT in Skeletal Muscle: Pitfalls and Pathologies.

Science.gov (United States)

Parida, Girish Kumar; Roy, Shambo Guha; Kumar, Rakesh

2017-07-01

FDG-PET/CT is an integral part of modern-day practice of medicine. By detecting increased cellular metabolism, FDG-PET/CT can help us detect infection, inflammatory disorders, or tumors, and also help us in prognostication of patients. However, one of the most important challenges is to correctly differentiate the abnormal uptake that is potentially pathologic from the physiological uptake. So while interpreting a PET/CT, one must be aware of normal biodistribution and different physiological variants of FDG uptake. Skeletal muscles constitute a large part of our body mass and one of the major users of glucose. Naturally, they are often the site of increased FDG uptake in a PET study. We as a nuclear medicine physician must be aware of all the pitfalls of increased skeletal muscle uptake to differentiate between physiological and pathologic causes. In this review, we have discussed the different causes and patterns of physiological FDG uptake in skeletal muscles. This knowledge of normal physiological variants of FDG uptake in the skeletal muscles is essential for differentiating pathologic uptake from the physiological ones. Also, we reviewed the role of FDG-PET/CT in various benign and malignant diseases involving skeletal muscle. Copyright © 2017 Elsevier Inc. All rights reserved.

Muscle glycogen content and glucose uptake during exercise in humans: influence of prior exercise and dietary manipulation

DEFF Research Database (Denmark)

Steensberg, Adam; van Hall, Gerrit; Keller, Charlotte

2002-01-01

on two occasions: one after 60 min of two-legged cycling (16 h prior to the experimental trial) followed by a high carbohydrate diet (HCHO) and the other after the same exercise followed by a low carbohydrate diet (LCHO) (Series 2). Muscle glycogen was decreased by 40 % when comparing the pre-exercised......There are many factors that can influence glucose uptake by contracting skeletal muscle during exercise and although one may be intramuscular glycogen content, this relationship is at present not fully elucidated. To test the hypothesis that muscle glycogen concentration influences glucose uptake...... during exercise, 13 healthy men were studied during two series of experiments. Seven men completed 4 h of two-legged knee extensor exercise 16 h after reducing of muscle glycogen by completing 60 min of single-legged cycling (Series 1). A further six men completed 3 h of two-legged knee extensor exercise...

Dihydrotestosterone stimulates amino acid uptake and the expression of LAT2 in mouse skeletal muscle fibres through an ERK1/2-dependent mechanism

Science.gov (United States)

Hamdi, M M; Mutungi, G

2011-01-01

Abstract Dihydrotestosterone (DHT) has acute/non-genomic actions in adult mammalian skeletal muscles whose physiological functions are still poorly understood. Therefore, the primary aim of this study was to investigate the acute/non-genomic effects of DHT on amino acid uptake as well as the cellular signal transduction events underlying these actions in mouse fast- and slow-twitch skeletal muscle fibre bundles. 14C-Labelled amino acids were used to investigate the effects of DHT and testosterone (T) on amino acid uptake and pharmacological interventions were used to determine the cellular signal transduction events mediating these actions. While T had no effect on the uptake of isoleucine (Ile) and α-methylaminoisobutyric acid (MeAIB) in both fibre types, DHT increased their uptake in the fast-twitch fibre bundles. This effect was reversed by inhibitors of protein translation, the epidermal growth factor receptor (EGFR), system A, system L, mTOR and MEK. However, it was relatively insensitive to inhibitors of transcription, androgen receptors and PI3K/Akt. Additionally, DHT treatment increased the expression of LAT2 and the phosphorylation of the EGFR in the fast-twitch fibre bundles and that of ERK1/2, RSK1/2 and ATF2 in both fibre types. Also, it decreased the phosphorylation of eEF2 and increased the incorporation of Ile into proteins in both fibre types. Most of these effects were reversed by EGFR and MEK inhibitors. From these findings we suggest that another physiological function of the acute/non-genomic actions of DHT in isolated mammalian skeletal muscle fibres is to stimulate amino acid uptake. This effect is mediated through the EGFR and involves the activation of the MAPK pathway and an increase in LAT2 expression. PMID:21606113

Reduced malonyl-CoA content in recovery from exercise correlates with improved insulin-stimulated glucose uptake in human skeletal muscle

DEFF Research Database (Denmark)

Frøsig, Christian; Roepstorff, Carsten; Brandt, Nina

2009-01-01

This study evaluated whether improved insulin-stimulated glucose uptake in recovery from acute exercise coincides with reduced malonyl-CoA (MCoA) content in human muscle. Furthermore, we investigated whether a high-fat diet [65 energy-% (Fat)] would alter the content of MCoA and insulin action...... to be compromised, although to a minor extent, by the Fat diet. Collectively, this study indicates that reduced muscle MCoA content in recovery from exercise may be part of the adaptive response leading to improved insulin action on glucose uptake after exercise in human muscle....

Direct effects of FGF21 on glucose uptake in human skeletal muscle

DEFF Research Database (Denmark)

Mashili, Fredirick L; Austin, Reginald L; Deshmukh, Atul S

2011-01-01

21 were determined in normal glucose tolerant (n = 40) and type 2 diabetic (T2D; n = 40) subjects. We determined whether FGF21 has direct effects on glucose metabolism in cultured myotubes (n = 8) and extensor digitorum longus skeletal muscle. RESULTS: Serum FGF21 levels increased 20% in T2D versus...... normal glucose tolerant subjects (p muscle mRNA expression was unaltered. Fasting insulin, homeostatic model assessment of insulin resistance (HOMA-IR), waist circumference, and body mass index (BMI) significantly correlated with serum FGF21 levels in T2D (p ... and insulin-stimulated glucose uptake in human myotubes, coincident with increased glucose transporter 1 mRNA, and enhanced glucose transporter 1 abundance at the plasma membrane. In isolated extensor digitorum longus muscle, FGF21 potentiated insulin-stimulated glucose transport, without altering...

α-MSH stimulates glucose uptake in mouse muscle and phosphorylates Rab-GTPase-activating protein TBC1D1 independently of AMPK

DEFF Research Database (Denmark)

Møller, Cathrine Laustrup; Kjøbsted, Rasmus; Enriori, Pablo J

2016-01-01

The melanocortin system includes five G-protein coupled receptors (family A) defined as MC1R-MC5R, which are stimulated by endogenous agonists derived from proopiomelanocortin (POMC). The melanocortin system has been intensely studied for its central actions in body weight and energy expenditure...... pathway involved in α-MSH-stimulated glucose uptake in differentiated L6 myotubes and mouse muscle explants. In order to examine the involvement of AMPK, we investigate -MSH stimulation in both wild type and AMPK deficient mice. We found that -MSH significantly induces phosphorylation of TBC1 domain (TBC1...

Hydroxylamine enhances glucose uptake in C2C12 skeletal muscle cells through the activation of insulin receptor substrate 1.

Science.gov (United States)

Kimura, Taro; Kato, Eisuke; Machikawa, Tsukasa; Kimura, Shunsuke; Katayama, Shinji; Kawabata, Jun

2014-02-28

Diabetes mellitus is a global disease, and the number of patients with it is increasing. Of various agents for treatment, those that directly act on muscle are currently attracting attention because muscle is one of the main tissues in the human body, and its metabolism is decreased in type II diabetes. In this study, we found that hydroxylamine (HA) enhances glucose uptake in C2C12 myotubes. Analysis of HA's mechanism revealed the involvement of IRS1, PI3K and Akt that is related to the insulin signaling pathway. Further investigation about the activation mechanism of insulin receptor or IRS1 by HA may provide a way to develop a novel anti-diabetic agent alternating to insulin. Copyright © 2014 Elsevier Inc. All rights reserved.

MRI findings of muscle involvement in idiopathic hypereosinophilic syndrome

International Nuclear Information System (INIS)

Hundt, W.; Staebler, A.; Reiser, M.

1999-01-01

A 40-year-old white man presented with fever, muscle pain, skin nodules and persistent hypereosinophilia over a period of 1 year. In addition, he had ventricular arrhythmias with episodes of tachycardia. Besides a lack of response to antiparasitic therapy, laboratory and pathological data excluded the diagnosis of trichinosis or any other parasitic infection. The patient's course of the disease over the previous 1 1 / 2 years was compatible with hypereosinophilic syndrome. In a muscle biopsy several eosinophilic perivascular and leucocytic intravascular infiltrates were found, indicative of muscle involvement by the disease. This is a report on the MRI findings of muscle involvement in idiopathic hypereosinophilic syndrome. (orig.)

25(OHD3 Levels Relative to Muscle Strength and Maximum Oxygen Uptake in Athletes

Directory of Open Access Journals (Sweden)

Książek Anna

2016-04-01

Full Text Available Vitamin D is mainly known for its effects on the bone and calcium metabolism. The discovery of Vitamin D receptors in many extraskeletal cells suggests that it may also play a significant role in other organs and systems. The aim of our study was to assess the relationship between 25(OHD3 levels, lower limb isokinetic strength and maximum oxygen uptake in well-trained professional football players. We enrolled 43 Polish premier league soccer players. The mean age was 22.7±5.3 years. Our study showed decreased serum 25(OHD3 levels in 74.4% of the professional players. The results also demonstrated a lack of statistically significant correlation between 25(OHD3 levels and lower limb muscle strength with the exception of peak torque of the left knee extensors at an angular velocity of 150°/s (r=0.41. No significant correlations were found between hand grip strength and maximum oxygen uptake. Based on our study we concluded that in well-trained professional soccer players, there was no correlation between serum levels of 25(OHD3 and muscle strength or maximum oxygen uptake.

MRI findings of muscle involvement in idiopathic hypereosinophilic syndrome

Energy Technology Data Exchange (ETDEWEB)

Hundt, W.; Staebler, A.; Reiser, M. [Department of Diagnostic Radiology, Klinikum Grosshadern, Muenchen (Germany)

1999-04-01

A 40-year-old white man presented with fever, muscle pain, skin nodules and persistent hypereosinophilia over a period of 1 year. In addition, he had ventricular arrhythmias with episodes of tachycardia. Besides a lack of response to antiparasitic therapy, laboratory and pathological data excluded the diagnosis of trichinosis or any other parasitic infection. The patient`s course of the disease over the previous 1{sup 1}/{sub 2} years was compatible with hypereosinophilic syndrome. In a muscle biopsy several eosinophilic perivascular and leucocytic intravascular infiltrates were found, indicative of muscle involvement by the disease. This is a report on the MRI findings of muscle involvement in idiopathic hypereosinophilic syndrome. (orig.) With 3 figs., 25 refs.

Low blood flow at onset of moderate intensity exercise does not limit muscle oxygen uptake

DEFF Research Database (Denmark)

Nyberg, Michael Permin; Mortensen, Stefan Peter; Saltin, Bengt

2010-01-01

The effect of low blood flow at onset of moderate intensity exercise on the rate of rise in muscle oxygen uptake was examined. Seven male subjects performed a 3.5 minute one-legged knee-extensor exercise bout (24+/-1 (+/-S.D.) W) without (CON) and with (double blockade; DB) arterial infusion of i....... Additionally, prostanoids and/or NO appear to play important roles in elevating skeletal muscle blood flow in the initial phase of exercise. Key words: Oxygen delivery, oxygen extraction, nitric oxide, prostanoids.......The effect of low blood flow at onset of moderate intensity exercise on the rate of rise in muscle oxygen uptake was examined. Seven male subjects performed a 3.5 minute one-legged knee-extensor exercise bout (24+/-1 (+/-S.D.) W) without (CON) and with (double blockade; DB) arterial infusion...... of inhibitors of nitric oxide synthase (NOS; L-NMMA) and cyclooxygenase (COX; indomethacin) in order to inhibit the synthesis of nitric oxide (NO) and prostanoids, respectively.. Leg blood flow and leg oxygen delivery throughout exercise was 25-50 % lower (P

Effects of xylitol on carbohydrate digesting enzymes activity, intestinal glucose absorption and muscle glucose uptake: a multi-mode study.

Science.gov (United States)

Chukwuma, Chika Ifeanyi; Islam, Md Shahidul

2015-03-01

The present study investigated the possible mechanism(s) behind the effects of xylitol on carbohydrate digesting enzymes activity, muscle glucose uptake and intestinal glucose absorption using in vitro, ex vivo and in vivo experimental models. The effects of increasing concentrations of xylitol (2.5%-40% or 164.31 mM-2628.99 mM) on alpha amylase and alpha glucosidase activity in vitro and intestinal glucose absorption and muscle glucose uptake were investigated under ex vivo conditions. Additionally, the effects of an oral bolus dose of xylitol (1 g per kg BW) on gastric emptying and intestinal glucose absorption and digesta transit in the different segments of the intestinal tract were investigated in normal and type 2 diabetic rats at 1 hour after dose administration, when phenol red was used as a recovery marker. Xylitol exhibited concentration-dependent inhibition of alpha amylase (IC₅₀ = 1364.04 mM) and alpha glucosidase (IC₅₀ = 1127.52 mM) activity in vitro and small intestinal glucose absorption under ex vivo condition. Xylitol also increased dose dependent muscle glucose uptake with and without insulin, although the uptake was not significantly affected by the addition of insulin. Oral single bolus dose of xylitol significantly delayed gastric emptying, inhibited intestinal glucose absorption but increased the intestinal digesta transit rate in both normal and diabetic rats compared to their respective controls. The data of this study suggest that xylitol reduces intestinal glucose absorption via inhibiting major carbohydrate digesting enzymes, slowing gastric emptying and fastening the intestinal transit rate, but increases muscle glucose uptake in normal and type 2 diabetic rats.

Rac1 governs exercise-stimulated glucose uptake in skeletal muscle through regulation of GLUT4 translocation in mice

DEFF Research Database (Denmark)

Sylow, Lykke; Laurent, Ida; Kleinert, Maximilian

2016-01-01

is a candidate molecule. This study investigated the role of Rac1 in muscle glucose uptake and substrate utilization during treadmill exercise in mice in vivo. Exercise-induced uptake of radiolabelled 2-deoxyglucose (2-DG) at 65% max running capacity was blocked in soleus and decreased by 80 and 60...

Pseudomalignant myositis ossificans involving multiple masticatory muscles: Imaging evaluation

International Nuclear Information System (INIS)

Kamalapur, Muralidhar G; Patil, Pritam B; Joshi, Shyamsundar; Shastri, Dinesh

2014-01-01

Myositis ossificans is a rare cause of trismus. We present a case of pseudomalignant myositis ossificans involving medial pterygoid, lateral pterygoid, and temporalis muscles. Patient presented with gross limitation in mouth opening. There was no history of trauma. Computed tomography (CT) images revealed a bone density mass located in the region of medial and lateral pterygoid muscles on the right and temporalis muscle on the left. Magnetic resonance imaging (MRI) showed similar findings. Radiological diagnosis was pseudomalignant myositis ossificans. The masses were resected and histopathologic examination confirmed the above diagnosis. This report describes the characteristic CT and MRI features. The unique feature of this case is the absence of history of trauma with involvement of multiple masticatory muscles, which, to the best of our knowledge, has not been reported before

Sorbitol increases muscle glucose uptake ex vivo and inhibits intestinal glucose absorption ex vivo and in normal and type 2 diabetic rats.

Science.gov (United States)

Chukwuma, Chika Ifeanyi; Islam, Md Shahidul

2017-04-01

Previous studies have suggested that sorbitol, a known polyol sweetener, possesses glycemic control potentials. However, the effect of sorbitol on intestinal glucose absorption and muscle glucose uptake still remains elusive. The present study investigated the effects of sorbitol on intestinal glucose absorption and muscle glucose uptake as possible anti-hyperglycemic or glycemic control potentials using ex vivo and in vivo experimental models. Sorbitol (2.5% to 20%) inhibited glucose absorption in isolated rat jejuna (IC 50 = 14.6% ± 4.6%) and increased glucose uptake in isolated rat psoas muscle with (GU 50 = 3.5% ± 1.6%) or without insulin (GU 50 = 7.0% ± 0.5%) in a concentration-dependent manner. Furthermore, sorbitol significantly delayed gastric emptying, accelerated digesta transit, inhibited intestinal glucose absorption, and reduced blood glucose increase in both normoglycemic and type 2 diabetic rats after 1 h of coingestion with glucose. Data of this study suggest that sorbitol exhibited anti-hyperglycemic potentials, possibly via increasing muscle glucose uptake ex vivo and reducing intestinal glucose absorption in normal and type 2 diabetic rats. Hence, sorbitol may be further investigated as a possible anti-hyperglycemic sweetener.

Ischaemia and insulin, but not ischaemia and contraction, act synergistically in stimulating muscle glucose uptake in vivo in humans.

NARCIS (Netherlands)

Bosselaar, M.; Smits, P.; Tack, C.J.J.

2009-01-01

Ischaemia, like muscle contraction, has been reported to induce skeletal muscle glucose uptake in in vitro models. This stimulating effect appears independent of insulin and is probably mediated by activation of AMPK (AMP-activated protein kinase). In the present study, we hypothesized that in vivo

CT, Magnetic Resonance, and 18F-Fluorodeoxyglucose Positron Emission Tomography/CT Imaging Features of Mucosa-Associated Lymphoid Tissue Lymphoma Involving Medial Rectus Muscle: A Case Report

International Nuclear Information System (INIS)

Lee, Sang Kwon; Choe, Mi Sun

2013-01-01

We report a case of mucosa-associated lymphoid tissue (MALT) lymphoma involving the medial rectus muscle in a 47-year-old man along with CT, MRI, 18 F-fluorodeoxy-glucose positron emission tomography/CT ( 18 F-FDG PET/CT), and pathologic features. The lesion was manifested as a fusiform enlargement isolated to the right medial rectus muscle with involvement of its tendinous insertion. The lesion was isoattenuating to the brain on non-enhanced CT images, showing as isointense to gray matter on fast spin echo T1- and T2-weighted images with fat saturation, and showed homogeneous enhancement on contrast-enhanced CT and MR images. The maximum stan- dardized uptake value on 18 F-FDG PET/CT was 4.9 g/mL. The results of histological and immunohistochemical examinations of the specimen obtained by biopsy of the right medial rectus muscle were consistent with MALT lymphoma. It should be noted that the extraocular muscle (EOM) is a rare location for the involvement of MALT lympho- ma, and MALT lymphoma of the EOM may mimic thyroid orbitopathy.

Technetium-99m labeled antisense probes uptake in vascular smooth muscle cells

International Nuclear Information System (INIS)

Zhang, Y.X.; Qin, G.M.; An, R.; Cao, G.X.; Cao, W.; Gao, Z.R.

2002-01-01

In the arterial wall, smooth muscle cells (SMC) normally exist in a quiescent, differentiated state, representing the contractile phenotype. During the development of atherosclerosis SMC change towards the synthetic phenotype going along with proliferation, chemotactic response and increased monocyte binding. The Fas/Fas ligand/caspase death-signaling pathway, Bcl-2 protein family/mitochondria, the tumor suppressive gene p53, and the proto-oncogene c-myc may be activated in atherosclerotic lesions, and mediates vascular apoptosis during the development of atherosclerosis. The atherosclerotic plaques contained 3-4 fold more c-myc mRNA than those in the normal aortic arteries, while increased Bax and Bak coupled with lack/paucity of Bcl-2 and Bcl-xL are associated with SMC apoptosis in advanced lesions. Methods: 1 Oligonucleotide Conjugation: A solution of single stranded amine-derivatized DNA (100-1000μg) was prepared at a concentration of 2 mg/ml in 0.25M sodium bicarbonate, 1 M sodium chloride, 1mM EDTA, pH8.5. Cell uptake studies: 99m Tc- MAG 3 -DNA radioactivity incorporation into porcine coronary smooth muscle cells in the log and plateau phases, respectively, was determined after different times of incubation at 37. The influence of extracellular 99m Tc- MAG 3 -DNA concentration on SMC uptake was also analyzed. [Results] Essentially complete conjugation was achieved by reverse-phase Sep-Pak C18 chromatography analysis. The MAG 3 -DNA was labeled with 99m Tc at room temperature and neutral pH, with a mean labeling efficiency of 80.11%(s.d=2.96%,n=4). The labeled antisense DNA still remained the ability to hybridize with its complementary DNA. After labeling, the stability of the DNA in saline or serum was retained as determined by reverse-phase Sep-Pak C18 chromatography analysis, except a shift at 30 min in serum incubation that suggesting a short time serum protein binding. 99m Tc-MAG 3 -c-myc uptake plateaued at 60 min and was directly proportional to the

Rac1 and AMPK Account for the Majority of Muscle Glucose Uptake Stimulated by Ex Vivo Contraction but Not In Vivo Exercise

DEFF Research Database (Denmark)

Sylow, Lykke; Møller, Lisbeth; Kleinert, Maximilian

2017-01-01

, but whether those two signaling pathways jointly account for the entire signal to glucose transport is unknown. We therefore studied the ability of contraction and exercise to stimulate glucose transport in isolated muscles with AMPK loss of function combined with either pharmacological inhibition or genetic...... uptake in vivo was only partially reduced by Rac1 mKO with no additive effect of a2KD. It is concluded that Rac1 and AMPK together account for almost the entire ex vivo contraction response in muscle glucose transport, whereas only Rac1, but not a2 AMPK, regulates muscle glucose uptake during submaximal...

Quantification, Variability, and Reproducibility of Basal Skeletal Muscle Glucose Uptake in Healthy Humans Using 18F-FDG PET/CT.

Science.gov (United States)

Gheysens, Olivier; Postnov, Andrey; Deroose, Christophe M; Vandermeulen, Corinne; de Hoon, Jan; Declercq, Ruben; Dennie, Justin; Mixson, Lori; De Lepeleire, Inge; Van Laere, Koen; Klimas, Michael; Chakravarthy, Manu V

2015-10-01

The quantification and variability of skeletal muscle glucose utilization (SMGU) in healthy subjects under basal (low insulin) conditions are poorly known. This information is essential early in clinical drug development to effectively interrogate novel pharmacologic interventions that modulate glucose uptake. The aim of this study was to determine test-retest characteristics and variability of SMGU within and between healthy subjects under basal conditions. Furthermore, different kinetic modeling strategies were evaluated to find the best-fitting model to assess SMGU studied by 18F-FDG. Six healthy male volunteers underwent 2 dynamic 18F-FDG PET/CT scans with an interval of 24 h. Subjects were admitted to the clinical unit to minimize variability in daily activities and food intake and restrict physical activity. 18F-FDG PET/CT scans of gluteal and quadriceps muscle area were obtained with arterial input. Regions of interest were drawn over the muscle area to obtain time-activity curves and standardized uptake values (SUVs) between 60 and 90 min. Spectral analysis of the data and kinetic modeling was performed using 2-tissue-irreversible (2T3K), 2-tissue-reversible, and 3-tissue-sequential-irreversible (3T5KS) models. Reproducibility was assessed by intraclass correlation coefficients (ICCs) and within-subject coefficient of variation (WSCV). SUVs in gluteal and quadriceps areas were 0.56±0.09 and 0.64±0.07. ICCs (with 90% confidence intervals in parentheses) were 0.88 (0.64-0.96) and 0.96 (0.82-0.99), respectively, for gluteal and quadriceps muscles, and WSCV for gluteal and quadriceps muscles was 2.2% and 3.6%, respectively. The rate of glucose uptake into muscle was 0.0016±0.0004 mL/mL⋅min, with an ICC of 0.94 (0.93-0.95) and WSCV of 6.6% for the 3T5KS model, whereas an ICC of 0.98 (0.92-1.00) and WSCV of 2.8% was obtained for the 2T3K model. 3T5KS demonstrated the best fit to the measured experimental points. Minimal variability in skeletal muscle glucose

CT, Magnetic Resonance, and {sup 18}F-Fluorodeoxyglucose Positron Emission Tomography/CT Imaging Features of Mucosa-Associated Lymphoid Tissue Lymphoma Involving Medial Rectus Muscle: A Case Report

Energy Technology Data Exchange (ETDEWEB)

Lee, Sang Kwon; Choe, Mi Sun [Dongsan Medical Center, Keimyung University School of Medicine, Daegu (Korea, Republic of)

2013-06-15

We report a case of mucosa-associated lymphoid tissue (MALT) lymphoma involving the medial rectus muscle in a 47-year-old man along with CT, MRI, 18 F-fluorodeoxy-glucose positron emission tomography/CT ( 18 F-FDG PET/CT), and pathologic features. The lesion was manifested as a fusiform enlargement isolated to the right medial rectus muscle with involvement of its tendinous insertion. The lesion was isoattenuating to the brain on non-enhanced CT images, showing as isointense to gray matter on fast spin echo T1- and T2-weighted images with fat saturation, and showed homogeneous enhancement on contrast-enhanced CT and MR images. The maximum stan- dardized uptake value on 18 F-FDG PET/CT was 4.9 g/mL. The results of histological and immunohistochemical examinations of the specimen obtained by biopsy of the right medial rectus muscle were consistent with MALT lymphoma. It should be noted that the extraocular muscle (EOM) is a rare location for the involvement of MALT lympho- ma, and MALT lymphoma of the EOM may mimic thyroid orbitopathy.

Activation of muscarinic M-1 cholinoceptors by curcumin to increase glucose uptake into skeletal muscle isolated from Wistar rats.

Science.gov (United States)

Cheng, Tse-Chou; Lin, Chian-Shiung; Hsu, Chih-Chieh; Chen, Li-Jen; Cheng, Kai-Chun; Cheng, Juei-Tang

2009-11-20

Curcumin, an active principle contained in rhizome of Curcuma longa, has been mentioned to show merit for diabetes through its anti-oxidative and anti-inflammatory properties. In the present study, we found that curcumin caused a concentration-dependent increase of glucose uptake into skeletal muscle isolated from Wistar rats. This action was inhibited by pirenzepine at concentration enough to block muscarinic M-1 cholinoceptor (M(1)-mAChR). In radioligand binding assay, the binding of [(3)H]-pirenzepine was also displaced by curcumin in a concentration-dependent manner. In the presence of inhibitors for PLC-PI3K pathway, either U73122 (phospholipase C inhibitor) or LY294002 (phosphoinositide 3-kinase inhibitor), curcumin-stimulated glucose uptake into skeletal muscle was markedly reduced. In Western blotting analysis, the membrane protein level of glucose transporter 4 (GLUT4) increased by curcumin was also reversed by blockade of M(1)-mAChR or PLC-PI3K pathway in a same manner. In conclusion, the obtained results suggest that curcumin can activate M(1)-mAChR at concentrations lower than to scavenge free radicals for increase of glucose uptake into skeletal muscle through PLC-PI3-kinase pathway.

Akt and Rac1 signalling are jointly required for insulin-stimulated glucose uptake in skeletal muscle and downregulated in insulin resistance

DEFF Research Database (Denmark)

Sylow, Lykke; Kleinert, Maximilian; Pehmøller, Christian

2014-01-01

Skeletal muscle plays a major role in regulating whole body glucose metabolism. Akt and Rac1 are important regulators of insulin-stimulated glucose uptake in skeletal muscle. However the relative role of each pathway and how they interact is not understood. Here we delineate how Akt and Rac1...... pathways signal to increase glucose transport independently of each other and are simultaneously downregulated in insulin resistant muscle. Pharmacological inhibition of Rac1 and Akt signalling was used to determine the contribution of each pathway to insulin-stimulated glucose uptake in mouse muscles....... The actin filament-depolymerizing agent LatrunculinB was combined with pharmacological inhibition of Rac1 or Akt, to examine whether either pathway mediates its effect via the actin cytoskeleton. Akt and Rac1 signalling were investigated under each condition, as well as upon Akt2 knockout and in ob/ob mice...

Distribution of skeletal muscle involvement in autosomal recessive distal muscular dystrophy

International Nuclear Information System (INIS)

Mizusawa, Hidehiro; Nakanishi, Takao; Kobayashi, Fumie.

1987-01-01

Distribution of skeletal muscle involvement in 5 cases with autosomal recessive distal muscular dystrophy was studied clinically and by computed tomography (CT). Manual muscle test showed muscle involvement with a predilection for flexors in the lower leg and adductors in the thigh. Flexion and extension of the thigh and the lower leg was impaired to similar degree. In progressed cases, neck flexors and trunk muscles were also affected mildly. CT disclosed more clearly the preferential involvement of flexors in the lower leg, and involvement of both hamstrings · adductors group and extensors group of the thigh to similar degree. However, m. popliteus was curiously well preserved. In addition, there was a stage showing high density and hypertrophy of m. sartorius, m. gracilis, m. adductor, m. biceps femoris, m. semimenbranosus, m. semitendinosus or m. rectus femoris, which in thought to be compensatory hypertrophy. M. gluteus minimus in the pelvic girdle and m. dorsi proprii in the trunk were also liable to be affected. The CT findings are regarded as characteristic features noted clearly before muscle weakness and atrophy become apparent clinically. CT is very useful for distinguishing distal muscular dystrophy from rimmed vacuolar distal myopathy in which m. quadriceps femoris and flexors of the lower leg are usually well preserved without compensatory hypertrophy on CT. (author)

Effects of 12-wk eccentric calf muscle training on muscle-tendon glucose uptake and SEMG in patients with chronic Achilles tendon pain

DEFF Research Database (Denmark)

Masood, Tahir; Kalliokoski, Kari; Magnusson, S Peter

2014-01-01

High-load eccentric exercises have been a key component in the conservative management of chronic Achilles tendinopathy. This study investigated the effects of a 12-wk progressive, home-based eccentric rehabilitation program on ankle plantar flexors' glucose uptake (GU) and myoelectric activity......, while the asymptomatic leg displayed higher uptake for medial gastrocnemius and flexor hallucis longus (P tendon GU than the controls (P effect on the tendon GU. Concerning SEMG, at baseline, soleus showed more relative...... within- or between-group differences. Eccentric rehabilitation was effective in decreasing subjective severity of Achilles tendinopathy. It also resulted in redistribution of relative electrical activity, but not metabolic activity, within the triceps surae muscle....

Circulating Docosahexaenoic Acid Associates with Insulin-Dependent Skeletal Muscle and Whole Body Glucose Uptake in Older Women Born from Normal Weight Mothers

Directory of Open Access Journals (Sweden)

Robert M. Badeau

2017-02-01

Full Text Available Background: Obesity among pregnant women is common, and their offspring are predisposed to obesity, insulin resistance, and diabetes. The circulating metabolites that are related to insulin resistance and are associated with this decreased tissue-specific uptake are unknown. Here, we assessed metabolite profiles in elderly women who were either female offspring from obese mothers (OOM or offspring of lean mothers (OLM. Metabolic changes were tested for associations with metrics for insulin resistance. Methods: Thirty-seven elderly women were separated into elderly offspring from obese mothers (OOM; n = 17 and elderly offspring from lean/normal weight mothers (OLM; n = 20 groups. We measured plasma metabolites using proton nuclear magnetic resonance (1H-NMR and insulin-dependent tissue-specific glucose uptake in skeletal muscle was assessed. Associations were made between metabolites and glucose uptake. Results: Compared to the OLM group, we found that the docosahexaenoic acid percentage of the total long-chain n-3 fatty acids (DHA/FA was significantly lower in OOM (p = 0.015. DHA/FA associated significantly with skeletal muscle glucose uptake (GU (p = 0.031 and the metabolizable glucose value derived from hyperinsulinemic-euglycemic clamp technique (M-value in the OLM group only (p = 0.050. Conclusions: DHA/FA is associated with insulin-dependent skeletal muscle glucose uptake and this association is significantly weakened in the offspring of obese mothers.

Astragalus Polysaccharide Suppresses Skeletal Muscle Myostatin Expression in Diabetes: Involvement of ROS-ERK and NF-κB Pathways

Directory of Open Access Journals (Sweden)

Min Liu

2013-01-01

Full Text Available Objective. The antidiabetes drug astragalus polysaccharide (APS is capable of increasing insulin sensitivity in skeletal muscle and improving whole-body glucose homeostasis. Recent studies suggest that skeletal muscle secreted growth factor myostatin plays an important role in regulating insulin signaling and insulin resistance. We hypothesized that regulation of skeletal muscle myostatin expression may be involved in the improvement of insulin sensitivity by APS. Methods. APS was administered to 13-week-old diabetic KKAy and nondiabetic C57BL/6J mice for 8 weeks. Complementary studies examined APS effects on the saturated acid palmitate-induced insulin resistance and myostatin expression in C2C12 cells. Results. APS treatment ameliorated hyperglycemia, hyperlipidemia, and insulin resistance and decreased the elevation of myostatin expression and malondialdehyde production in skeletal muscle of noninsulin-dependent diabetic KKAy mice. In C2C12 cells in vitro, saturated acid palmitate-induced impaired glucose uptake, overproduction of ROS, activation of extracellular regulated protein kinases (ERK, and NF-κB were partially restored by APS treatment. The protective effects of APS were mimicked by ERK and NF-κB inhibitors, respectively. Conclusion. Our study demonstrates elevated myostatin expression in skeletal muscle of type 2 diabetic KKAy mice and in cultured C2C12 cells exposed to palmitate. APS is capable of improving insulin sensitivity and decreasing myostatin expression in skeletal muscle through downregulating ROS-ERK-NF-κB pathway.

Growth factor involvement in tension-induced skeletal muscle growth

Science.gov (United States)

Vandenburgh, Herman H.

1993-01-01

Long-term manned space travel will require a better understanding of skeletal muscle atrophy which results from microgravity. Astronaut strength and dexterity must be maintained for normal mission operations and for emergency situations. Although exercise in space slows the rate of muscle loss, it does not prevent it. A biochemical understanding of how gravity/tension/exercise help to maintain muscle size by altering protein synthesis and/or degradation rate should ultimately allow pharmacological intervention to prevent muscle atrophy in microgravity. The overall objective is to examine some of the basic biochemical processes involved in tension-induced muscle growth. With an experimental in vitro system, the role of exogenous and endogenous muscle growth factors in mechanically stimulated muscle growth are examined. Differentiated avian skeletal myofibers can be 'exercised' in tissue culture using a newly developed dynamic mechanical cell stimulator device which simulates different muscle activity patterns. Patterns of mechanical activity which significantly affect muscle growth and metabolic characteristics were found. Both exogenous and endogenous growth factors are essential for tension-induced muscle growth. Exogenous growth factors found in serum, such as insulin, insulin-like growth factors, and steroids, are important regulators of muscle protein turnover rates and mechanically-induced muscle growth. Endogenous growth factors are synthesized and released into the culture medium when muscle cells are mechanically stimulated. At least one family of mechanically induced endogenous factors, the prostaglandins, help to regulate the rates of protein turnover in muscle cells. Endogenously synthesized IGF-1 is another. The interaction of muscle mechanical activity and these growth factors in the regulation of muscle protein turnover rates with our in vitro model system is studied.

Genetic variation in ATP5O is associated with skeletal muscle ATP50 mRNA expression and glucose uptake in young twins.

Directory of Open Access Journals (Sweden)

Tina Rönn

Full Text Available BACKGROUND: Impaired oxidative capacity of skeletal muscle mitochondria contribute to insulin resistance and type 2 diabetes (T2D. Furthermore, mRNA expression of genes involved in oxidative phosphorylation, including ATP5O, is reduced in skeletal muscle from T2D patients. Our aims were to investigate mechanisms regulating ATP5O expression in skeletal muscle and association with glucose metabolism, and the relationship between ATP5O single nucleotide polymorphisms (SNPs and risk of T2D. METHODOLOGY/PRINCIPAL FINDINGS: ATP5O mRNA expression was analyzed in skeletal muscle from young (n = 86 and elderly (n = 68 non-diabetic twins before and after a hyperinsulinemic euglycemic clamp. 11 SNPs from the ATP5O locus were genotyped in the twins and a T2D case-control cohort (n = 1466. DNA methylation of the ATP5O promoter was analyzed in twins (n = 22 using bisulfite sequencing. The mRNA level of ATP5O in skeletal muscle was reduced in elderly compared with young twins, both during basal and insulin-stimulated conditions (p<0.0005. The degree of DNA methylation around the transcription start of ATP5O was <1% in both young and elderly twins and not associated with mRNA expression (p = 0.32. The mRNA level of ATP5O in skeletal muscle was positively related to insulin-stimulated glucose uptake (regression coefficient = 6.6; p = 0.02. Furthermore, two SNPs were associated with both ATP5O mRNA expression (rs12482697: T/T versus T/G; p = 0.02 and rs11088262: A/A versus A/G; p = 0.004 and glucose uptake (rs11088262: A/A versus A/G; p = 0.002 and rs12482697: T/T versus T/G; p = 0.005 in the young twins. However, we could not detect any genetic association with T2D. CONCLUSIONS/SIGNIFICANCE: Genetic variation and age are associated with skeletal muscle ATP5O mRNA expression and glucose disposal rate, suggesting that combinations of genetic and non-genetic factors may cause the reduced expression of ATP5O in T2D muscle. These findings propose a role for ATP5O, in

Ca2+ uptake and cellular integrity in rat EDL muscle exposed to electrostimulation, electroporation, or A23187

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Gissel, Hanne; Clausen, Torben

2003-01-01

We tested the hypothesis that increased Ca2+ uptake in rat extensor digitorum longus (EDL) muscle elicits cell membrane damage as assessed from release of the intracellular enzyme lactate dehydrogenase (LDH). This was done by using 1) electrostimulation, 2) electroporation, and 3) the Ca2+ ionoph...

Lactate, Glucose and Oxygen Uptake in Human Brain During Recovery from Maximal Exercise

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Kojiro, I.; Schmalbruch, I.K.; Quistorff, B.

1999-01-01

Skeletal muscle, brain lactate uptake, brain oxygen uptake, energy metabolism, brain glucose uptake......Skeletal muscle, brain lactate uptake, brain oxygen uptake, energy metabolism, brain glucose uptake...

Exercising with blocked muscle glycogenolysis

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Nielsen, Tue L; Pinós, Tomàs; Brull, Astrid

2018-01-01

BACKGROUND: McArdle disease (glycogen storage disease type V) is an inborn error of skeletal muscle metabolism, which affects glycogen phosphorylase (myophosphorylase) activity leading to an inability to break down glycogen. Patients with McArdle disease are exercise intolerant, as muscle glycogen......-derived glucose is unavailable during exercise. Metabolic adaptation to blocked muscle glycogenolysis occurs at rest in the McArdle mouse model, but only in highly glycolytic muscle. However, it is unknown what compensatory metabolic adaptations occur during exercise in McArdle disease. METHODS: In this study, 8......-week old McArdle and wild-type mice were exercised on a treadmill until exhausted. Dissected muscles were compared with non-exercised, age-matched McArdle and wild-type mice for histology and activation and expression of proteins involved in glucose uptake and glycogenolysis. RESULTS: Investigation...

AMPK alpha1 activation is required for stimulation of glucose uptake by twitch contraction, but not by H2O2, in mouse skeletal muscle

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Jensen, Thomas Elbenhardt; Schjerling, Peter; Viollet, Benoit

2008-01-01

into muscle by certain stimuli. In contrast, no clear function has yet been determined for alpha(1) AMPK in skeletal muscle, possibly due to alpha-AMPK isoform signaling redundancy. By applying low-intensity twitch-contraction and H(2)O(2) stimulation to activate alpha(1) AMPK, but not alpha(2) AMPK......, in wildtype and alpha-AMPK transgenic mouse muscles, this study aimed to define conditions where alpha(1) AMPK is required to increase muscle glucose uptake. METHODOLOGY/PRINCIPAL FINDINGS: Following stimulation with H(2)O(2) (3 mM, 20 min) or twitch-contraction (0.1 ms pulse, 2 Hz, 2 min), signaling and 2......-deoxyglucose uptake were measured in incubated soleus muscles from wildtype and muscle-specific kinase-dead AMPK (KD), alpha(1) AMPK knockout or alpha(2) AMPK knockout mice. H(2)O(2) increased the activity of both alpha(1) and alpha(2) AMPK in addition to Akt phosphorylation, and H(2)O(2)-stimulated glucose...

Prior AICAR stimulation increases insulin sensitivity in mouse skeletal muscle in an AMPK-dependent manner

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Kjøbsted, Rasmus; Treebak, Jonas Thue; Fentz, Joachim

2015-01-01

Acute exercise increases glucose uptake in skeletal muscle by an insulin-independent mechanism. In the period after exercise insulin sensitivity to increase glucose uptake is enhanced. The molecular mechanisms underpinning this phenomenon are poorly understood, but appear to involve an increased ...

The suprachiasmatic nucleus drives day-night variations in postprandial triglyceride uptake into skeletal muscle and brown adipose tissue.

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Moran-Ramos, Sofía; Guerrero-Vargas, Natali N; Mendez-Hernandez, Rebeca; Basualdo, Maria Del Carmen; Escobar, Carolina; Buijs, Ruud M

2017-12-01

What is the central question of this study? What are the factors influencing day-night variations in postprandial triglycerides? What is the main finding and its importance? Rats show low postprandial plasma triglyceride concentrations early in the active period that are attributable to a higher uptake by skeletal muscle and brown adipose tissue. We show that these day-night variations in uptake are driven by the suprachiasmatic nucleus, probably via a Rev-erbα-mediated mechanism and independent of locomotor activity. These findings highlight that the suprachiasmatic nucleus has a major role in day-night variations in plasma triglycerides and that disturbances in our biological clock might be an important risk factor contributing to development of postprandial hyperlipidaemia. Energy metabolism follows a diurnal pattern, mainly driven by the suprachiasmatic nucleus (SCN), and disruption of circadian regulation has been linked to metabolic abnormalities. Indeed, epidemiological evidence shows that night work is a risk factor for cardiovascular disease, and postprandial hyperlipidaemia is an important contributor. Therefore, the aim of this work was to investigate the factors that drive day-night variations in postprandial triglycerides (TGs). Intact and SCN-lesioned male Wistar rats were subjected to an oral fat challenge during the beginning of the rest phase (day) or the beginning of the active phase (night). The plasma TG profile was evaluated and tissue TG uptake assayed. After the fat challenge, intact rats showed lower postprandial plasma TG concentrations early in the night when compared with the day. However, no differences were observed in the rate of intestinal TG secretion between day and night. Instead, there was a higher uptake of TG by skeletal muscle and brown adipose tissue early in the active phase (night) when compared with the rest phase (day), and these variations were abolished in rats bearing bilateral SCN lesions. Rev-erbα gene expression

Skeletal muscle blood flow and oxygen uptake at rest and during exercise in humans: a PET study with nitric oxide and cyclooxygenase inhibition

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Heinonen, Ilkka; Saltin, Bengt; Kemppainen, Jukka

2011-01-01

The aim of the present study was to determine the effect of nitric oxide and prostanoids on microcirculation and oxygen uptake specifically in the active skeletal muscle by use of positron emission tomography (PET). Healthy males performed 3 five min bouts of light knee-extensor exercise. Skeletal...... muscle blood flow and oxygen uptake were measured at rest and during the exercise using PET with H(2)O(15) and (15)O(2) during: 1) control conditions; 2) nitric oxide synthase (NOS) inhibition by arterial infusion of L-NMMA and 3) combined NOS and cyclooxygenase (COX) inhibition by arterial infusion of L...

CUP-1 Is a Novel Protein Involved in Dietary Cholesterol Uptake in Caenorhabditis elegans

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Valdes, Victor J.; Athie, Alejandro; Salinas, Laura S.; Navarro, Rosa E.; Vaca, Luis

2012-01-01

Sterols transport and distribution are essential processes in all multicellular organisms. Survival of the nematode Caenorhabditis elegans depends on dietary absorption of sterols present in the environment. However the general mechanisms associated to sterol uptake in nematodes are poorly understood. In the present work we provide evidence showing that a previously uncharacterized transmembrane protein, designated Cholesterol Uptake Protein-1 (CUP-1), is involved in dietary cholesterol uptake in C. elegans. Animals lacking CUP-1 showed hypersensitivity to cholesterol limitation and were unable to uptake cholesterol. A CUP-1-GFP fusion protein colocalized with cholesterol-rich vesicles, endosomes and lysosomes as well as the plasma membrane. Additionally, by FRET imaging, a direct interaction was found between the cholesterol analog DHE and the transmembrane “cholesterol recognition/interaction amino acid consensus” (CRAC) motif present in C. elegans CUP-1. In-silico analysis identified two mammalian homologues of CUP-1. Most interestingly, CRAC motifs are conserved in mammalian CUP-1 homologous. Our results suggest a role of CUP-1 in cholesterol uptake in C. elegans and open up the possibility for the existence of a new class of proteins involved in sterol absorption in mammals. PMID:22479487

The role of exercise-induced myokines in muscle homeostasis and the defense against chronic diseases

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Brandt, Claus; Pedersen, Bente K

2010-01-01

to our theory, such effects may in part be mediated via muscle-derived peptides, so-called "myokines". Contracting skeletal muscles release myokines with endocrine effects, mediating direct anti-inflammatory effects, and/or specific effects on visceral fat. Other myokines work locally within the muscle...... and exert their effects on signalling pathways involved in fat oxidation and glucose uptake. By mediating anti-inflammatory effects in the muscle itself, myokines may also counteract TNF-driven insulin resistance. In conclusion, exercise-induced myokines appear to be involved in mediating both systemic...

Effect of lifelong football training on the expression of muscle molecular markers involved in healthy longevity.

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Mancini, A; Vitucci, D; Labruna, G; Imperlini, E; Randers, M B; Schmidt, J F; Hagman, M; Andersen, T R; Russo, R; Orrù, S; Krustrup, P; Salvatore, F; Buono, P

2017-04-01

We investigated whether lifelong football training affects the expression of healthy longevity-related muscle molecular markers. Biopsies were collected from the vastus lateralis muscle of 10 lifelong football-trained men (68.2 ± 3.0 years) and of 10 active untrained healthy men (66.7 ± 1.3 years). Gene and protein expression was measured by RTqPCR on RNA and by western blotting on protein extracts from muscle biopsies, respectively. The expression of AMPKα1/α2, NAMPT, TFAM and PGC1α, which are markers of oxidative metabolism, and MyHC β isoform expression was higher in the muscle of football-trained men vs untrained men. Also citrate synthase activity was higher in trained than in untrained men (109.3 ± 9.2 vs 75.1 ± 9.2 mU/mg). These findings were associated with a healthier body composition in trained than in untrained men [body weight: 78.2 ± 6.5 vs 91.2 ± 11.2 kg; body mass index BMI: 24.4 ± 1.6 vs 28.8 ± 4.0 kg m -2 ; fat%: 22.6 ± 8.0 vs 31.4 ± 5.0%)] and with a higher maximal oxygen uptake (VO 2 max: 34.7 ± 3.8 vs 27.3 ± 4.0 ml/min/kg). Also the expression of proteins involved in DNA repair and in senescence suppression (Erk1/2, Akt and FoxM1) was higher in trained than in untrained men. At BMI- and age-adjusted multiple linear regression analysis, fat percentage was independently associated with Akt protein expression, and VO 2 max was independently associated with TFAM mRNA and with Erk1/2 protein expression. Lifelong football training increases the expression of key markers involved in muscle oxidative metabolism, and in the DNA repair and senescence suppression pathways, thus providing the molecular basis for healthy longevity.

Differential glucose uptake in quadriceps and other leg muscles during one-legged dynamic submaximal knee-extension exercise

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Kalliokoski, Kari K; Boushel, Robert; Langberg, Henning

2011-01-01

One-legged dynamic knee-extension exercise (DKE) is a widely used model to study the local cardiovascular and metabolic responses to exercise of the quadriceps muscles. In this study, we explored the extent to which different muscles of the quadriceps are activated during exercise using positron...... emission tomography (PET) determined uptake of [18F]-fluoro-deoxy-glucose (GU) during DKE. Five healthy male subjects performed DKE at 25 W for 35 min and both the contracting and contralateral resting leg were scanned with PET from mid-thigh and distally. On average, exercise GU was the highest...

Acute interleukin-6 administration does not impair muscle glucose uptake or whole-body glucose disposal in healthy humans

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Steensberg, Adam; Fischer, Christian P; Sacchetti, Massimo

2003-01-01

adrenaline (epinephrine). IL-6 infusion, irrespective of dose, did not result in any changes to endogenous glucose production, whole-body glucose disposal or leg- glucose uptake. These data demonstrate that acute IL-6 administration does not impair whole-body glucose disposal, net leg-glucose uptake......The cytokine interleukin (IL)-6 has recently been linked with type 2 diabetes mellitus and has been suggested to affect glucose metabolism. To determine whether acute IL-6 administration affects whole-body glucose kinetics or muscle glucose uptake, 18 healthy young men were assigned to one of three...... the cessation of infusion (recovery) to determine endogenous glucose production and whole-body glucose disposal. Infusion with HiIL-6 and LoIL-6 resulted in a marked (P

Whole-body muscle MRI in 20 patients suffering from late onset Pompe disease: Involvement patterns.

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Carlier, Robert-Yves; Laforet, Pascal; Wary, Claire; Mompoint, Dominique; Laloui, Kenza; Pellegrini, Nadine; Annane, Djillali; Carlier, Pierre G; Orlikowski, David

2011-11-01

To describe muscle involvement on whole-body MRI scans in adult patients at different stages of late-onset Pompe disease. Twenty patients aged 37 to 75 were examined. Five were bedridden and required ventilatory support. Axial and coronal T1 turbo-spin-echo sequences were performed on 1.5T or 3T systems. MRI was scored for 47 muscles using Mercuri's classification. Whole-body scans were obtained with a mean in-room time of 29 min. Muscle changes consisted of internal bright signals of fatty replacement without severe retraction of the muscles' corpus. Findings were consistent with previous descriptions of spine extensors and pelvic girdle, but also provided new information on recurrent muscle changes particularly in the tongue and subscapularis muscle. Moreover thigh involvement was more heterogeneous than previously described, in terms of distribution across muscles as well as with respect to the overall clinical presentation. Whole-body MRI provides a very evocative description of muscle involvement in Pompe disease in adults. Copyright © 2011 Elsevier B.V. All rights reserved.

DiabetterTM Reduces Post Meal Hyperglycemia Via Enhancement Of Glucose Uptake Into Adipocytes And Muscles Cells

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Zainah Adam; Shafii Khamis

2014-01-01

Currently, there are lots of herbal products available in local markets that are used for treatment of diabetes mellitus. Most of these products are not standardized and lack of efficacy and safety data. DiaBetterTM is one of the local herbal products that have been used for treatment of diabetes. This study was carried out to determine the efficacy of DiaBetterTM in reducing hyperglycemia and to elucidate the mechanisms by which hyperglycemia is reduced. Antihyperglycemic evaluation was done in normal and streptozotocin-induced diabetic rats at different prandial states and the antihyperglycemic mechanisms elucidation was carried out in muscle and adipocytes cells using glucose tracer method (2-deoxy-[1-3H]-glucose). The results showed that DiaBetterTM significantly reduced post meal hyperglycemia in normal and diabetic rats, and improved glucose tolerance activity in diabetic rats particularly after 4 and 6 hours of administration. Antihyperglycemic mechanisms elucidation revealed that the DiaBetterTM significantly enhanced insulin-stimulated glucose uptake into adipocytes and muscle cells, with the highest magnitude of enhancement were 1.54-fold (p<0.01) and 1.46-fold (p<0.001), respectively. Molecular mechanisms that responsible for this enhancement were the increment of insulin sensitivity at cells membrane. Cytotoxic evaluation was also done and confirmed that DiaBetterTM was toxicologically safe against muscle and adipocytes cells. In conclusion, post-meal antihyperglycemic and glucose tolerance activity activity of DiaBetterTM was mediated through the enhancement of glucose uptake into adipocytes and muscle cells. Insulin sensitizing activity showed by DiaBetterTM suggests that this product has the potential to ameliorate insulin resistance condition. Therefore, it is suggested that DiaBetterTM can be used as dietary adjunct for the treatment of type 2 diabetes mellitus which related to insulin resistance. (author)

Glucose uptake of the muscle and adipose tissues in diabetes and obesity disease models. Evaluation of insulin and β3-adrenergic receptor agonist effects by 18F-FDG

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Ishino, Seigo; Sugita, Taku; Kondo, Yusuke

2017-01-01

One of the major causes of diabetes and obesity is abnormality in glucose metabolism and glucose uptake in the muscle and adipose tissue based on an insufficient action of insulin. Therefore, many of the drug discovery programs are based on the concept of stimulating glucose uptake in these tissues. Improvement of glucose metabolism has been assessed based on blood parameters, but these merely reflect the systemic reaction to the drug administered. We have conducted basic studies to investigate the usefulness of glucose uptake measurement in various muscle and adipose tissues in pharmacological tests using disease-model animals. A radiotracer for glucose, 18 F-2-deoxy-2-fluoro-D-glucose ( 18 F-FDG), was administered to Wistar fatty rats (type 2 diabetes model), DIO mouse (obese model), and the corresponding control animals, and the basal glucose uptake in the muscle and adipose (white and brown) tissues were compared using biodistribution method. Moreover, insulin and a β3 agonist (CL316, 243), which are known to stimulate glucose uptake in the muscle and adipose tissues, were administered to assess their effect. 18 F-FDG uptake in each tissue was measured as the radioactivity and the distribution was confirmed by autoradiography. In Wistar fatty rats, all the tissues measured showed a decrease in the basal level of glucose uptake when compared to Wistar lean rats. On the other hand, the same trend was observed only in the white adipose tissue in DIO mice, while brown adipose tissue showed increments in the basal glucose uptake in this model. Insulin administration stimulated glucose uptake in both Wistar lean and fatty rats, although the responses were inhibited in Wistar fatty rats. The same tendency was shown also in control mice, but clear increments in glucose uptake were not observed in the muscle and brown adipose tissue of DIO mice after insulin administration. β3 agonist administration showed the similar trend in Wistar lean and fatty rats as insulin

Skeletal muscle-specific expression of PGC-1α-b, an exercise-responsive isoform, increases exercise capacity and peak oxygen uptake.

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Miki Tadaishi

Full Text Available Maximal oxygen uptake (VO(2max predicts mortality and is associated with endurance performance. Trained subjects have a high VO(2max due to a high cardiac output and high metabolic capacity of skeletal muscles. Peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α, a nuclear receptor coactivator, promotes mitochondrial biogenesis, a fiber-type switch to oxidative fibers, and angiogenesis in skeletal muscle. Because exercise training increases PGC-1α in skeletal muscle, PGC-1α-mediated changes may contribute to the improvement of exercise capacity and VO(2max. There are three isoforms of PGC-1α mRNA. PGC-1α-b protein, whose amino terminus is different from PGC-1α-a protein, is a predominant PGC-1α isoform in response to exercise. We investigated whether alterations of skeletal muscle metabolism by overexpression of PGC-1α-b in skeletal muscle, but not heart, would increase VO(2max and exercise capacity.Transgenic mice showed overexpression of PGC-1α-b protein in skeletal muscle but not in heart. Overexpression of PGC-1α-b promoted mitochondrial biogenesis 4-fold, increased the expression of fatty acid transporters, enhanced angiogenesis in skeletal muscle 1.4 to 2.7-fold, and promoted exercise capacity (expressed by maximum speed by 35% and peak oxygen uptake by 20%. Across a broad range of either the absolute exercise intensity, or the same relative exercise intensities, lipid oxidation was always higher in the transgenic mice than wild-type littermates, suggesting that lipid is the predominant fuel source for exercise in the transgenic mice. However, muscle glycogen usage during exercise was absent in the transgenic mice.Increased mitochondrial biogenesis, capillaries, and fatty acid transporters in skeletal muscles may contribute to improved exercise capacity via an increase in fatty acid utilization. Increases in PGC-1α-b protein or function might be a useful strategy for sedentary subjects to perform exercise

Effects of exercise training and exhaustion on 45Ca uptake by rat skeletal muscle mitochondria and sarcoplasmic reticulum

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Bonner, H.W.; Leslie, S.W.; Combs, A.B.; Tate, C.A.

1976-01-01

Mitochondrial and sarcoplasmic reticular 45 Ca 2+ uptake and Ca 2+ -ATPase activity were determined in skeletal muscle from exercise trained and non-trained rats at rest or following short-term exhaustive exercise. In trained rats exercised to exhaustion, mitochondrial 45 Ca 2+ uptake was significantly depressed when compared to non-trained rats at rest. Ca 2+ -ATPase activity of sarcoplasmic reticulum from trained rats exercised to exhaustion was significantly increased as compared to trained rats at rest. These data suggest that the disruptive influence of Ca 2+ accumulation in mitochondria isolated following exhaustive exercise may be diminished as a result of training

Perceived Devaluation and STI Testing Uptake among a Cohort of Street-Involved Youth in a Canadian Setting.

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Karamouzian, Mohammad; Shoveller, Jean; Dong, Huiru; Gilbert, Mark; Kerr, Thomas; DeBeck, Kora

2017-10-01

Perceived devaluation has been shown to have adverse effects on the mental and physical health outcomes of people who use drugs. However, the impact of perceived devaluation on sexually transmitted infections (STI) testing uptake among street-involved youth, who face multiple and intersecting stigmas due to their association with drug use and risky sexual practices, has not been fully characterized. Data were obtained between December 2013 and November 2014 from a cohort of street-involved youth who use illicit drugs aged 14-26 in Vancouver, British Columbia. Multivariable generalized estimating equations were constructed to assess the independent relationship between perceived devaluation and STI testing uptake. Among 300 street-involved youth, 87.0% reported a high perceived devaluation score at baseline. In the multivariable analysis, high perceived devaluation was negatively associated with STI testing uptake after adjustment for potential confounders (Adjusted Odds Ratio = 0.38, 95% Confidence Interval 0.15-0.98). Perceived devaluation was high among street-involved youth in our sample and appears to have adverse effects on STI testing uptake. HIV prevention and care programs should be examined and improved to better meet the special needs of street-involved youth in non-stigmatizing ways.

Muscle insulin sensitivity and glucose metabolism are controlled by the intrinsic muscle clock★

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Dyar, Kenneth A.; Ciciliot, Stefano; Wright, Lauren E.; Biensø, Rasmus S.; Tagliazucchi, Guidantonio M.; Patel, Vishal R.; Forcato, Mattia; Paz, Marcia I.P.; Gudiksen, Anders; Solagna, Francesca; Albiero, Mattia; Moretti, Irene; Eckel-Mahan, Kristin L.; Baldi, Pierre; Sassone-Corsi, Paolo; Rizzuto, Rosario; Bicciato, Silvio; Pilegaard, Henriette; Blaauw, Bert; Schiaffino, Stefano

2013-01-01

Circadian rhythms control metabolism and energy homeostasis, but the role of the skeletal muscle clock has never been explored. We generated conditional and inducible mouse lines with muscle-specific ablation of the core clock gene Bmal1. Skeletal muscles from these mice showed impaired insulin-stimulated glucose uptake with reduced protein levels of GLUT4, the insulin-dependent glucose transporter, and TBC1D1, a Rab-GTPase involved in GLUT4 translocation. Pyruvate dehydrogenase (PDH) activity was also reduced due to altered expression of circadian genes Pdk4 and Pdp1, coding for PDH kinase and phosphatase, respectively. PDH inhibition leads to reduced glucose oxidation and diversion of glycolytic intermediates to alternative metabolic pathways, as revealed by metabolome analysis. The impaired glucose metabolism induced by muscle-specific Bmal1 knockout suggests that a major physiological role of the muscle clock is to prepare for the transition from the rest/fasting phase to the active/feeding phase, when glucose becomes the predominant fuel for skeletal muscle. PMID:24567902

Nerve and muscle involvement in mitochondrial disorders: an electrophysiological study.

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Mancuso, Michelangelo; Piazza, Selina; Volpi, Leda; Orsucci, Daniele; Calsolaro, Valeria; Caldarazzo Ienco, Elena; Carlesi, Cecilia; Rocchi, Anna; Petrozzi, Lucia; Calabrese, Rosanna; Siciliano, Gabriele

2012-04-01

Involvement of the peripheral nervous system in mitochondrial disorders (MD) has been previously reported. However, the exact prevalence of peripheral neuropathy and/or myopathy in MD is still unclear. In order to evaluate the prevalence of neuropathy and myopathy in MD, we performed sensory and motor nerve conduction studies (NCS) and concentric needle electromyography (EMG) in 44 unselected MD patients. NCS were abnormal in 36.4% of cases, and were consistent with a sensori-motor axonal multineuropathy (multifocal neuropathy), mainly affecting the lower limbs. EMG evidence of myopathy was present in 54.5% of patients, again mainly affecting the lower limbs. Nerve and muscle involvement was frequently subclinical. Peripheral nerve and muscle involvement is common in MD patients. Our study supports the variability of the clinical expression of MD. Further studies are needed to better understand the molecular basis underlying the phenotypic variability among MD patients.

The Rab-GTPase-activating protein TBC1D1 regulates skeletal muscle glucose metabolism

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Szekeres, Ferenc; Chadt, Alexandra; Tom, Robby Z

2012-01-01

The Rab-GTPase-activating protein TBC1D1 has emerged as a novel candidate involved in metabolic regulation. Our aim was to determine whether TBC1D1 is involved in insulin as well as energy-sensing signals controlling skeletal muscle metabolism. TBC1D1-deficient congenic B6.SJL-Nob1.10 (Nob1.10(SJL...... be explained partly by a 50% reduction in GLUT4 protein, since proximal signaling at the level of Akt, AMPK, and acetyl-CoA carboxylase (ACC) was unaltered. Paradoxically, in vivo insulin-stimulated 2-deoxyglucose uptake was increased in EDL and tibialis anterior muscle from TBC1D1-deficient mice......)) and wild-type littermates were studied. Glucose and insulin tolerance, glucose utilization, hepatic glucose production, and tissue-specific insulin-mediated glucose uptake were determined. The effect of insulin, AICAR, or contraction on glucose transport was studied in isolated skeletal muscle. Glucose...

The role of uncoupling protein 3 regulating calcium ion uptake into mitochondria during sarcopenia

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Nikawa, Takeshi; Choi, Inho; Haruna, Marie; Hirasaka, Katsuya; Maita Ohno, Ayako; Kondo Teshima, Shigetada

Overloaded mitochondrial calcium concentration contributes to progression of mitochondrial dysfunction in aged muscle, leading to sarcopenia. Uncoupling protein 3 (UCP3) is primarily expressed in the inner membrane of skeletal muscle mitochondria. Recently, it has been reported that UCP3 is associated with calcium uptake into mitochondria. However, the mechanisms by which UCP3 regulates mitochondrial calcium uptake are not well understood. Here we report that UCP3 interacts with HS-1 associated protein X-1 (Hax-1), an anti-apoptotic protein that is localized in mitochondria, which is involved in cellular responses to calcium ion. The hydrophilic sequences within the loop 2, matrix-localized hydrophilic domain of mouse UCP3 are necessary for binding to Hax-1 of the C-terminal domain in adjacent to mitochondrial innermembrane. Interestingly, these proteins interaction occur the calcium-dependent manner. Indeed, overexpression of UCP3 significantly enhanced calcium uptake into mitochondria on Hax-1 endogenously expressing C2C12 myoblasts. In addition, Hax-1 knock-down enhanced calcium uptake into mitochondria on both UCP3 and Hax-1 endogenously expressing C2C12 myotubes, but not myoblasts. Finally, the dissociation of UCP3 and Hax-1 enhances calcium uptake into mitochondria in aged muscle. These studies identify a novel UCP3-Hax-1 complex regulates the influx of calcium ion into mitochondria in muscle. Thus, the efficacy of UCP3-Hax-1 in mitochondrial calcium regulation may provide a novel therapeutic approach against mitochondrial dysfunction-related disease containing sarcopenia.

Greater glucose uptake heterogeneity in knee muscles of old compared to young men during isometric contractions detected by [18F]-FDG PET/CT

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Thorsten eRudroff

2014-05-01

Full Text Available We used positron emission tomography/computed tomography (PET/CT and [18F]-FDG to test the hypothesis that glucose uptake (GU heterogeneity in skeletal muscles as a measure of heterogeneity in muscle activity is greater in old than young men when they perform isometric contractions. Six young (26 ± 6 yrs and six old (77 ± 6 yrs men performed two types of submaximal isometric contractions that required either force or position control. [18F]-FDG was injected during the task and PET/CT scans were performed immediately after the task. Within-muscle heterogeneity of knee muscles was determined by calculating the coefficient of variation (CV of GU in PET image voxels within the muscles of interest. The average GU heterogeneity (mean ± SD for knee extensors and flexors was greater for the old (35.3 ± 3.3 % than the young (28.6 ± 2.4 % (P = 0.006. Muscle volume of the knee extensors were greater for the young compared to the old men (1016 ± 163 vs. 598 ± 70 cm3, P= 0.004. In a multiple regression model, knee extensor muscle volume was a predictor (partial r = - 0.87; P = 0.001 of GU heterogeneity for old men (R2 = 0.78; P < 0.001, and MVC force predicted GU heterogeneity for young men (partial r = - 0.95, P < 0.001. The findings demonstrate that glucose uptake is more spatially variable for old than young men and especially so for old men who exhibit greater muscle atrophy.

Phospholipase D1 mediates AMP-activated protein kinase signaling for glucose uptake.

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Jong Hyun Kim

2010-03-01

Full Text Available Glucose homeostasis is maintained by a balance between hepatic glucose production and peripheral glucose utilization. In skeletal muscle cells, glucose utilization is primarily regulated by glucose uptake. Deprivation of cellular energy induces the activation of regulatory proteins and thus glucose uptake. AMP-activated protein kinase (AMPK is known to play a significant role in the regulation of energy balances. However, the mechanisms related to the AMPK-mediated control of glucose uptake have yet to be elucidated.Here, we found that AMPK-induced phospholipase D1 (PLD1 activation is required for (14C-glucose uptake in muscle cells under glucose deprivation conditions. PLD1 activity rather than PLD2 activity is significantly enhanced by glucose deprivation. AMPK-wild type (WT stimulates PLD activity, while AMPK-dominant negative (DN inhibits it. AMPK regulates PLD1 activity through phosphorylation of the Ser-505 and this phosphorylation is increased by the presence of AMP. Furthermore, PLD1-S505Q, a phosphorylation-deficient mutant, shows no changes in activity in response to glucose deprivation and does not show a significant increase in (14C-glucose uptake when compared to PLD1-WT. Taken together, these results suggest that phosphorylation of PLD1 is important for the regulation of (14C-glucose uptake. In addition, extracellular signal-regulated kinase (ERK is stimulated by AMPK-induced PLD1 activation through the formation of phosphatidic acid (PA, which is a product of PLD. An ERK pharmacological inhibitor, PD98059, and the PLD inhibitor, 1-BtOH, both attenuate (14C-glucose uptake in muscle cells. Finally, the extracellular stresses caused by glucose deprivation or aminoimidazole carboxamide ribonucleotide (AICAR; AMPK activator regulate (14C-glucose uptake and cell surface glucose transport (GLUT 4 through ERK stimulation by AMPK-mediated PLD1 activation.These results suggest that AMPK-mediated PLD1 activation is required for (14C

Unilateral Muscle Artifacts due to Non-compliance During Uptake Phase of 18F-FDG PET/CT in an Oncologic Patient

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William Makis

2018-02-01

Full Text Available A 49-year-old male patient with a prior history of poor compliance with medical appointments was referred for an 18F-fluoro-2-deoxy-D-glucose (18F-FDG positron emission tomography/computed tomography (PET/CT for the staging of a rectal squamous cell carcinoma. The PET/CT showed unilateral diffuse skeletal muscle 18F-FDG uptake as well as bilateral salivary gland uptake artifacts, suggestive of non-compliance with patient preparation instructions. The PET/CT nurse noted that during the 18F-FDG uptake phase, the patient appeared intoxicated, and she found two beer cans hidden in the waste disposal beside his chair just prior to imaging. The patient only admitted to eating a cookie approximately 30 minutes after the injection of 18F-FDG PET/CT and denied consuming alcohol during the uptake phase. We present the imaging findings of non-compliance with patient instructions during the uptake phase of 18F-FDG.

Characteristic of muscle involvement evaluated by CT scans in early stages of progressive muscular dystrophy

International Nuclear Information System (INIS)

Arai, Yumi

1993-01-01

Muscle CT scans were performed in order to compare the characteristic distribution of progressive muscle involvement in the early stages of Duchenne type (DMD) and Fukuyama type muscular dystrophy (FCMD). Muscle images at the levels of the 3rd lumbar vertebra, thigh and calf were assessed by visual inspection, and mean CT numbers calculated for individual muscles were statistically analysed. On visual inspection, intramuscular low density areas and muscular atrophy were observed in the muscles of older patients with either disease. These changes were, however, more extensive at thigh level in DMD, and at calf level in FCMD. Nevertheless, the mean CT numbers of muscles in which only slight changes were grossly visible on CT scans displayed progressive decreases with increasing age. Moreover, a significant negative relationship was recognizable between age and mean CT number in almost all muscles examined. Comparison of the slopes of the regression lines revealed that the so-called selective pattern of muscle involvement characteristic of the symptomatic stage had already partially manifested in the preclinical or early stages of both diseases. In FCMD, the rates of decrease in CT numbers were extremely rapid for calf muscles as compared with those in DMD, indicating that this is one reason for FCMD patients never becoming ambulatory. However, for almost all of the other muscles, the CT numbers in FCMD decreased in parallel with the corresponding CT numbers in DMD; thus, these diseases displayed a similarity in the pattern of muscle involvement, despite their different pathogenetic mechanisms and inheritance patterns. (author)

Significance of insulin for glucose metabolism in skeletal muscle during contractions

DEFF Research Database (Denmark)

Hespel, P; Vergauwen, Lieven; Vandenberghe, K

1996-01-01

is essentially effected via increased blood flow, significantly contributes to stimulate glucose uptake. Again, however, increased glucose delivery appears to be a more potent stimulus of muscle glucose uptake as the circulating insulin level is increased. Furthermore, contractions and elevated flow prove...... is effected primarily via mechanisms exerted within the muscle cell related to the contractile activity per se. Yet contractions become a more potent stimulus of muscle glucose uptake as the plasma insulin level is increased. In addition, enhanced glucose delivery to muscle, which during exercise...... to be additive stimuli of muscle glucose uptake at any plasma insulin level. In conclusion, the extent to which muscle glucose uptake is stimulated during exercise depends on various factors, including 1) the intensity of the contractile activity, 2) the magnitude of the exercise-associated increase in muscle...

Diabetter"T"M Reduces Post Meal Hyperglycemia Via Enhancement of Glucose Uptake Into Adipocytes and Muscles Cells

International Nuclear Information System (INIS)

Zainah Adam; Mohd Hishamudin Mohd Jinal; Alqarni Bader Ayed; Shafii Khamis

2014-01-01

There are lots of herbal products for diabetes mellitus treatment available in local market. Most of these products are not standardized and lack of efficacy and safety data. DiaBetter"T"M is one of the herbal products that have been used for diabetes treatment. This study was carried out to determine the efficacy of DiaBetter"T"M in reducing hyperglycemia and to elucidate the mechanisms by which hyperglycemia is reduced. The results showed that DiaBetter"T"M significantly reduced post meal hyperglycemia in normal and diabetic rats, and improved glucose tolerance activity in diabetic rats particularly after 4 and 6 hours of administration. Antihyperglycemic mechanisms elucidation revealed that the DiaBetter"T"M significantly enhanced insulin-stimulated glucose uptake into adipocytes and muscle cells, with the highest magnitude of enhancement were 1.54 fold (p<0.01) and 1.46 fold (p<0.001), respectively. Molecular mechanisms that responsible for this enhancement were the increment of insulin sensitivity at cells membrane. Cytotoxic evaluation was also done and confirmed that DiaBetter"T"M was toxicologically safe against muscle and adipocytes cells. In conclusion, post-meal antihyperglycemic and glucose tolerance activity of DiaBetter"T"M was mediated through the enhancement of glucose uptake into adipocytes and muscle cells. Insulin sensitizing activity showed by DiaBetter"T"M suggests that this product has the potential to ameliorate insulin resistance condition. Therefore, it is suggested that the DiaBetter"T"M can be used as dietary adjunct for the management of type 2 diabetes mellitus which related to insulin resistance. (Author)

Comparative microscopic and biochemical study of the uptake of fluorescent and 125I-labeled lipoproteins by skin fibroblasts, smooth muscle cells, and peritoneal macrophages in culture

International Nuclear Information System (INIS)

Reynolds, G.D.; St Clair, R.W.

1985-01-01

Uptake of low density lipoprotein (LDL) and of acetyl LDL was compared in skin fibroblasts, smooth muscle cells, and peritoneal macrophages with the use of lipoproteins labeled with either 125 I or the fluorescent probe 3,3'-dioctadecylindocarbocyanine (DiI). The uptake of DiI-labeled lipoproteins was assessed by quantitative spectrofluorometry and by fluorescence microscopy. The DiI was quantitatively retained by the cells, while the 125 I-LDL was degraded and 125 I-labeled degradation products were excreted from the cells. In smooth muscle cells and fibroblasts the uptake of LDL was virtually the same whether measured with the use of the DiI or 125 I-label. The labeling of acetyl LDL with DiI enhanced its uptake in peritoneal macrophages by an average of 18%. With the DiI label, lipoprotein uptake could be determined after as little as 10 minutes of incubation at 37 C. The pattern of uptake of the DiI-labeled lipoproteins was consistent with binding to specific receptors, because no DiI could be detected in mutant cells without LDL receptors, and uptake was competitively inhibited by addition of excess unlabeled lipoprotein. When the DiI-labeled lipoproteins were removed from the medium, there was a 5-15% loss of DiI from all cell types studied over the first 24 hours

Maltitol inhibits small intestinal glucose absorption and increases insulin mediated muscle glucose uptake ex vivo but not in normal and type 2 diabetic rats.

Science.gov (United States)

Chukwuma, Chika Ifeanyi; Ibrahim, Mohammed Auwal; Islam, Md Shahidul

2017-02-01

This study investigated the effects of maltitol on intestinal glucose absorption and muscle glucose uptake using ex vivo and in vivo experimental models. The ex vivo experiment was conducted in isolated jejunum and psoas muscle from normal rats. The in vivo study investigated the effects of a single bolus dose of maltitol on gastric emptying, intestinal glucose absorption and digesta transit in normal and type 2 diabetic rats. Maltitol inhibited glucose absorption in isolated rat jejunum and increased glucose uptake in isolated rat psoas muscle in the presence of insulin but not in the absence of insulin. In contrast, maltitol did not significantly (p > 0.05) alter small intestinal glucose absorption or blood glucose levels as well as gastric emptying and digesta transit in normal or type 2 diabetic rats. The results suggest that maltitol may not be a suitable dietary supplement for anti-diabetic food and food products to improve glycemic control.

Glucose uptake heterogeneity of the leg muscles is similar between patients with multiple sclerosis and healthy controls during walking.

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Kindred, John H; Ketelhut, Nathaniel B; Rudroff, Thorsten

2015-02-01

Difficulties in ambulation are one of the main problems reported by patients with multiple sclerosis. A previous study by our research group showed increased recruitment of muscle groups during walking, but the influence of skeletal muscle properties, such as muscle fiber activity, has not been fully elucidated. The purpose of this investigation was to use the novel method of calculating glucose uptake heterogeneity in the leg muscles of patients with multiple sclerosis and compare these results to healthy controls. Eight patients with multiple sclerosis (4 men) and 8 healthy controls (4 men) performed 15 min of treadmill walking at a comfortable self-selected speed following muscle strength tests. Participants were injected with ≈ 8 mCi of [(18)F]-fluorodeoxyglucose during walking after which positron emission tomography/computed tomography imaging was performed. No differences in muscle strength were detected between multiple sclerosis and control groups (P>0.27). Within the multiple sclerosis, group differences in muscle volume existed between the stronger and weaker legs in the vastus lateralis, semitendinosus, and semimembranosus (Pmuscle group or individual muscle of the legs (P>0.16, P≥0.05). Patients with multiple sclerosis and healthy controls showed similar muscle fiber activity during walking. Interpretations of these results, with respect to our previous study, suggest that walking difficulties in patients with multiple sclerosis may be more associated with altered central nervous system motor patterns rather than alterations in skeletal muscle properties. Published by Elsevier Ltd.

Muscle involvement during intermittent contraction patterns with different target force feedback modes

DEFF Research Database (Denmark)

Sjøgaard, G; Jørgensen, L V; Ekner, D

2000-01-01

and following 30 min of intermittent contractions showed larger fatigue development with proprioceptive feedback than visual feedback. Also rating of perceived exertion increased more during proprioceptive feedback than visual feedback. This may in part be explained by small differences in the mechanics during......: Feedback mode significantly effects the muscle involvement and fatigue during intermittent contractions. RelevanceIntermittent contractions are common in many work places and various feedback modes are being given regarding work requirements. The choice of feedback may significantly affect the muscle load...... and consequently the development muscle fatigue and disorders....

Identification of residues of FpvA involved in the different steps of Pvd-Fe uptake in Pseudomonas aeruginosa.

Science.gov (United States)

Nader, Mirella; Dobbelaere, Wim; Vincent, Michel; Journet, Laure; Adams, Hendrik; Cobessi, David; Gallay, Jacques; Schalk, Isabelle J

2007-10-23

FpvA is an outer membrane transporter involved in iron uptake by the siderophore pyoverdine (Pvd) in Pseudomonas aeruginosa. This transporter, like all other proteins of the same family, consists of a transmembrane 22 beta-stranded barrel occluded by a plug domain. The beta-strands of the barrel are connected by large extracellular loops and short periplasmic turns. Site-directed mutagenesis was carried out on FpvA to identify the extracellular loops or parts of these loops involved in the various stages of Pvd-Fe uptake. The G286C, W362C, and W434C mutations in loops L1, L3, and L4, respectively, disturbed the binding of the apo siderophore, as shown by time-resolved fluorescence spectroscopy. Iron uptake experiments followed by fluorescence resonance energy transfer (FRET) or using 55Fe indicated that residues W434 and G701 and, therefore, loops L4 and L9 must be involved in Pvd-Fe uptake by FpvA. The two corresponding mutants incorporated smaller than normal amounts of 55Fe into cells, and no Pvd recycling on FpvA was observed after iron release. Surprisingly, the S603C mutation in loop L7 increased the amount of Pvd-Fe transported. Our results suggest that W434 (L4), S603 (L7), and G701 (L9) are involved in the mechanism of Pvd-Fe uptake.

Thyroid-Associated Orbitopathy with Superior Oblique Muscle Involvement: A Case Report

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Horng-Jiun Wu

2004-02-01

Full Text Available A 29-year-old male with a 5-year-history of hyperthyroidism complained of diplopia and proptosis. After subtotal thyroidectomy, he still had diplopia in a certain gaze. Computerized tomography showed inferior rectus muscle enlargement in the right eye and inferior rectus, medial rectus, and superior oblique muscle enlargement in the left eye. Ocular examination with the cover and uncover test revealed hyperphoria and exophoria in the left eye. The upward gaze of the right eye was more limited than that of the left eye. Since superior oblique muscle involvement in patients with thyroid orbitopathy is quite rare, we discuss its effect on ocular motility in patients with thyroid-associated orbitopathy.

Primary non-Hodgkin lymphoma of skeletal muscle: imaging findings

International Nuclear Information System (INIS)

Zhou Liangping; Peng Weijun; Tang Feng; Mao Jian; Yang Wentao

2006-01-01

Objective: To analyze the imaging manifestations of primary non-Hodgkin lymphoma of skeletal muscle and improve the recognition of this rare disease. Methods: Five cases of primary non- Hodgkin lymphoma of skeletal muscle proved pathologically underwent imaging exam, including MRI and CT in 3 cases, only MRI in 1 case, only CT in 1 case, X-ray in 2 cases and bone scintigraphy in 2 cases. Results: Diffuse enlargements of involved muscle with presentation of overall configuration were observed in all five cases. All 4 cases manifested as homogeneous soft masses, which is isoattenuating to normal muscle on unenhanced CT images. After intravenous injection of contrast media, the masses enhanced homogeneously and slightly (2 cases) or moderately (1 case) on CT images. The lesions were homogenous and had isointense or slightly low signal intensity compared with that of uninvolved muscle on T 1 -weighted images and high signal intensity on T 2 -weighted images. After intravenous injection of contrast media, all 2 cases enhanced homogeneously and moderately with the enhanced signal intensity of involved muscle greatly higher than that of uninvolved muscle on MR images. Two cases of X-ray plain showed no destruction of bone and 2 cases of bone scintigraphy exams showed increased radiotracer uptake of involved muscle with no infiltration of bone marrow. Conclusion: There are several characteristics on the imaging of primary non-Hodgkin lymphoma of skeletal muscle. MRI is the optimal imaging method for the diagnosis of this disease. (authors)

The digastric muscle is less involved in pharyngeal swallowing in rabbits.

Science.gov (United States)

Tsujimura, Takanori; Yamada, Aki; Nakamura, Yuki; Fukuhara, Takako; Yamamura, Kensuke; Inoue, Makoto

2012-06-01

The swallowing reflex is centrally programmed by the lower brain stem, the so-called swallowing central pattern generator (CPG), and once the reflex is initiated, many muscles in the oral, pharyngeal, laryngeal, and esophageal regions are systematically activated. The mylohyoid (MH) muscle has been considered to be a "leading muscle" according to previous studies, but the functional role of the digastric (DIG) muscle in the swallowing reflex remains unclear. In the present study, therefore, the activities of single units of MH and DIG neurons were recorded extracellularly, and the functional involvement of these neurons in the swallowing reflex was investigated. The experiments were carried out on eight adult male Japanese white rabbits anesthetized with urethane. To identify DIG and MH neurons, the peripheral nerve (either DIG or MH) was stimulated to evoke action potentials of single motoneurons. Motoneurons were identified as such if they either (1) responded to antidromic nerve stimulation of DIG or MH in an all-or-none manner at threshold intensities and (2) followed stimulation frequencies of up to 0.5 kHz. As a result, all 11 MH neurons recorded were synchronously activated during the swallowing reflex, while there was no activity in any of the 7 DIG neurons recorded during the swallowing reflex. All neurons were anatomically localized ventromedially at the level of the caudal portion of the trigeminal motor nucleus, and there were no differences between the MH and DIG neuron sites. The present results strongly suggest that at least in the rabbit, DIG motoneurons are not tightly controlled by the swallowing CPG and, hence, the DIG muscle is less involved in the swallowing reflex.

The relationship between skeletal muscle mitochondrial citrate synthase activity and whole body oxygen uptake adaptations in response to exercise training

DEFF Research Database (Denmark)

Vigelsø, Andreas; Andersen, Nynne B; Dela, Flemming

2014-01-01

Citrate synthase (CS) activity is a validated biomarker for mitochondrial density in skeletal muscle. CS activity is also used as a biochemical marker of the skeletal muscle oxidative adaptation to a training intervention, and a relationship between changes in whole body aerobic capacity and chan......Citrate synthase (CS) activity is a validated biomarker for mitochondrial density in skeletal muscle. CS activity is also used as a biochemical marker of the skeletal muscle oxidative adaptation to a training intervention, and a relationship between changes in whole body aerobic capacity...... and changes in CS activity is often assumed. However, this relationship and absolute values of CS and maximal oxygen uptake (V.O2max) has never been assessed across different studies. A systematic PubMed search on literature published from 1983 to 2013 was performed. The search profile included: citrate...... and CS activity. 70 publications with 97 intervention groups were included. There was a positive (r = 0.45) correlation (P

Assessment of muscle function using hybrid PET/MRI

DEFF Research Database (Denmark)

Haddock, Bryan; Holm, Søren; Poulsen, Jákup M.

2017-01-01

-FDG while activating the quadriceps of one leg with repeated knee extension exercises followed by hand-grip exercises for one arm. Immediately following the exercises, the subjects were scanned simultaneously with 18F-FDG PET/MRI and muscle groups were evaluated for increases in 18F-FDG uptake and MRI T2......Purpose: The aim of this study was to determine the relationship between relative glucose uptake and MRI T2 changes in skeletal muscles following resistance exercise using simultaneous PET/MRI scans. Methods: Ten young healthy recreationally active men (age 21 – 28 years) were injected with 18F...... values. Results: A significant linear correlation between 18F-FDG uptake and changes in muscle T2 (R2 = 0.71) was found. for both small and large muscles and in voxel to voxel comparisons. Despite large intersubject differences in muscle recruitment, the linear correlation between 18F-FDG uptake...

Effects of 12-wk eccentric calf muscle training on muscle-tendon glucose uptake and SEMG in patients with chronic Achilles tendon pain.

Science.gov (United States)

Masood, Tahir; Kalliokoski, Kari; Magnusson, S Peter; Bojsen-Møller, Jens; Finni, Taija

2014-07-15

High-load eccentric exercises have been a key component in the conservative management of chronic Achilles tendinopathy. This study investigated the effects of a 12-wk progressive, home-based eccentric rehabilitation program on ankle plantar flexors' glucose uptake (GU) and myoelectric activity and Achilles tendon GU. A longitudinal study design with control (n = 10) and patient (n = 10) groups was used. Surface electromyography (SEMG) from four ankle plantar flexors and GU from the same muscles and the Achilles tendon were measured during submaximal intermittent isometric plantar flexion task. The results indicated that the symptomatic leg was weaker (P eccentric rehabilitation. Additionally, the rehabilitation resulted in greater GU in both soleus (P tendon GU than the controls (P effect on the tendon GU. Concerning SEMG, at baseline, soleus showed more relative activity in the symptomatic leg compared with both the asymptomatic and control legs (P Eccentric rehabilitation was effective in decreasing subjective severity of Achilles tendinopathy. It also resulted in redistribution of relative electrical activity, but not metabolic activity, within the triceps surae muscle. Copyright © 2014 the American Physiological Society.

Assessment of muscle function using hybrid PET/MRI: comparison of 18F-FDG PET and T2-weighted MRI for quantifying muscle activation in human subjects

International Nuclear Information System (INIS)

Haddock, Bryan; Holm, Soeren; Poulsen, Jakup M.; Enevoldsen, Lotte H.; Larsson, Henrik B.W.; Kjaer, Andreas; Suetta, Charlotte

2017-01-01

The aim of this study was to determine the relationship between relative glucose uptake and MRI T 2 changes in skeletal muscles following resistance exercise using simultaneous PET/MRI scans. Ten young healthy recreationally active men (age 21 - 28 years) were injected with 18 F-FDG while activating the quadriceps of one leg with repeated knee extension exercises followed by hand-grip exercises for one arm. Immediately following the exercises, the subjects were scanned simultaneously with 18 F-FDG PET/MRI and muscle groups were evaluated for increases in 18 F-FDG uptake and MRI T 2 values. A significant linear correlation between 18 F-FDG uptake and changes in muscle T 2 (R 2 = 0.71) was found. for both small and large muscles and in voxel to voxel comparisons. Despite large intersubject differences in muscle recruitment, the linear correlation between 18 F-FDG uptake and changes in muscle T 2 did not vary among subjects. This is the first assessment of skeletal muscle activation using hybrid PET/MRI and the first study to demonstrate a high correlation between 18 F-FDG uptake and changes in muscle T 2 with physical exercise. Accordingly, it seems that changes in muscle T 2 may be used as a surrogate marker for glucose uptake and lead to an improved insight into the metabolic changes that occur with muscle activation. Such knowledge may lead to improved treatment strategies in patients with neuromuscular pathologies such as stroke, spinal cord injuries and muscular dystrophies. (orig.)

Training-induced acceleration of oxygen uptake kinetics in skeletal muscle: the underlying mechanisms.

Science.gov (United States)

Zoladz, J A; Korzeniewski, B; Grassi, B

2006-11-01

It is well known that the oxygen uptake kinetics during rest-to-work transition (V(O2) on-kinetics) in trained subjects is significantly faster than in untrained individuals. It was recently postulated that the main system variable that determines the transition time (t(1/2)) of the V(O2) on-kinetics in skeletal muscle, at a given moderate ATP usage/work intensity, and under the assumption that creatine kinase reaction works near thermodynamic equilibrium, is the absolute (in mM) decrease in [PCr] during rest-to-work transition. Therefore we postulate that the training-induced acceleration of the V(O2) on-kinetics is a marker of an improvement of absolute metabolic stability in skeletal muscles. The most frequently postulated factor responsible for enhancement of muscle metabolic stability is the training-induced increase in mitochondrial proteins. However, the mechanism proposed by Gollnick and Saltin (1982) can improve absolute metabolic stability only if training leads to a decrease in resting [ADP(free)]. This effect is not observed in many examples of training causing an acceleration of the V(O2) on-kinetics, especially in early stages of training. Additionally, this mechanism cannot account for the significant training-induced increase in the relative (expressed in % or as multiples of the resting values) metabolic stability at low work intensities, condition in which oxidative phosphorylation is not saturated with [ADP(free)]. Finally, it was reported that in the early stage of training, acceleration in the V(O2) on-kinetics and enhancement of muscle metabolic stability may precede adaptive responses in mitochondrial enzymes activities or mitochondria content. We postulate that the training-induced acceleration in the V(O2) on-kinetics and the improvement of the metabolite stability during moderate intensity exercise in the early stage of training is mostly caused by an intensification of the "parallel activation" of ATP consumption and ATP supply pathways

The uptake of tritium-labelled carnitine by monolayer cultures of human fetal muscle and its potential as a label in cytotoxicity studies

International Nuclear Information System (INIS)

Cambridge, G.; Stern, C.M.M.

1981-01-01

As a novel approach to the investigation of immune responses directed against muscle antigens in inflammatory muscle disease, the use of tritium-labelled carnitine as a selective marker for myotubes in monolayer cultures was investigated. Tritium-labelled carnitine was incubated either with monolayer cultures of human fetal muscle or with syngeneic monolayer cultures of human fetal fibroblasts. The rate of uptake and loss of tritium-labelled carnitine by muscle cultures was compared with that shown by fibroblast cultures; values for the ratio Ksub(m)/Vsub(max) were 3.1 for muscle cultures and 0.46 for fibroblast cultures. Freeze-dried radioautographs of muscle monolayers, previously incubated with tritium-labelled carnitine confirmed the specific intra-tubular localization of the label. Fetal muscle monolayers, previously incubated with tritium-labelled carnitine, were used as targets in long-term cytotoxicity experiments into lymphocyte-mediated myotoxicity. Peripheral blood lymphocytes from patients with inflammatory muscle disease were shown to be myotoxic, but lymphocytes from normal individuals or those with non-inflammatory muscle disease were not. Carnitine-based measures of myotoxicity closely followed the clinical activity of the disease in one patient and the test shows considerable potential as a means of assessing myotube killing by lymphocytes on a per-cell basis. (author)

Subacute sarcoid myositis with ocular muscle involvement; a case report and review of the literature.

Science.gov (United States)

Hayashi, Y; Ishii, Yoshiki; Nagasawa, J; Arai, S; Okada, H; Ohmi, F; Umetsu, T; Machida, Y; Kurasawa, K; Takemasa, A; Suzuki, S; Senoh, T; Sada, T; Hirata, K

2016-10-07

Sarcoidosis is a chronic granulomatous disease that can affect multiple organs. The lungs, eyes, and skin are known to be highly affected organs in sarcoidosis. There have been reports based on random muscle biopsy that 32-80% of systemic sarcoidosis comprises noncaseating granulomas; however, muscle involvement in sarcoidosis is generally asymptomatic and has an unknown frequency. We describe a case of acute to subacute sarcoid myositis of the skeletal and extraocular muscles. Typical ophthalmic involvement (manifested by infiltration of the ocular adnexa, intraocular inflammation, or infiltration of the retrobulbar visual pathways) and extraocular sarcoid myositis (as with the present case) is infrequently reported. It is important to keep in mind the rare yet perhaps underestimated entity of sarcoid myositis, and to utilize muscle biopsy and imaging tests for appropriate diagnosis and management of patients with sarcoidosis.

Stimulatory effect of insulin on glucose uptake by muscle involves the central nervous system in insulin-sensitive mice

NARCIS (Netherlands)

Coomans, Claudia P.; Biermasz, Nienke R.; Geerling, Janine J.; Guigas, Bruno; Rensen, Patrick C. N.; Havekes, Louis M.; Romijn, Johannes A.

2011-01-01

Insulin inhibits endogenous glucose production (EGP) and stimulates glucose uptake in peripheral tissues. Hypothalamic insulin signaling is required for the inhibitory effects of insulin on EGP. We examined the contribution of central insulin signaling on circulating insulin-stimulated

Stimulatory effect of insulin on glucose uptake by muscle involves the central nervous system in insulin-sensitive mice

NARCIS (Netherlands)

Coomans, C.P.; Biermasz, N.R.; Geerling, J.J.; Guigas, B.; Rensen, P.C.N.; Havekes, L.M.; Romijn, J.A.

2011-01-01

OBJECTIVE - Insulin inhibits endogenous glucose production (EGP) and stimulates glucose uptake in peripheral tissues. Hypothalamic insulin signaling is required for the inhibitory effects of insulin on EGP. We examined the contribution of central insulin signaling on circulating insulin-stimulated

Assessment of muscle function using hybrid PET/MRI: comparison of {sup 18}F-FDG PET and T2-weighted MRI for quantifying muscle activation in human subjects

Energy Technology Data Exchange (ETDEWEB)

Haddock, Bryan; Holm, Soeren; Poulsen, Jakup M.; Enevoldsen, Lotte H.; Larsson, Henrik B.W.; Kjaer, Andreas; Suetta, Charlotte [Rigshospitalet Glostrup, Copenhagen University Hospital, Department of Clinical Physiology, Nuclear Medicine and PET, Glostrup (Denmark)

2017-04-15

The aim of this study was to determine the relationship between relative glucose uptake and MRI T{sub 2} changes in skeletal muscles following resistance exercise using simultaneous PET/MRI scans. Ten young healthy recreationally active men (age 21 - 28 years) were injected with {sup 18}F-FDG while activating the quadriceps of one leg with repeated knee extension exercises followed by hand-grip exercises for one arm. Immediately following the exercises, the subjects were scanned simultaneously with {sup 18}F-FDG PET/MRI and muscle groups were evaluated for increases in {sup 18}F-FDG uptake and MRI T{sub 2} values. A significant linear correlation between {sup 18}F-FDG uptake and changes in muscle T{sub 2} (R {sup 2} = 0.71) was found. for both small and large muscles and in voxel to voxel comparisons. Despite large intersubject differences in muscle recruitment, the linear correlation between {sup 18}F-FDG uptake and changes in muscle T{sub 2} did not vary among subjects. This is the first assessment of skeletal muscle activation using hybrid PET/MRI and the first study to demonstrate a high correlation between {sup 18}F-FDG uptake and changes in muscle T{sub 2} with physical exercise. Accordingly, it seems that changes in muscle T{sub 2} may be used as a surrogate marker for glucose uptake and lead to an improved insight into the metabolic changes that occur with muscle activation. Such knowledge may lead to improved treatment strategies in patients with neuromuscular pathologies such as stroke, spinal cord injuries and muscular dystrophies. (orig.)

Gallium uptake in tryptophan-related pulmonary disease

International Nuclear Information System (INIS)

Kim, S.M.; Park, C.H.; Intenzo, C.M.; Patel, R.

1991-01-01

We describe a patient who developed fever, fatigue, muscle weakness, dyspnea, skin rash, and eosinophilia after taking high doses of tryptophan for insomnia for two years. A gallium-67 scan revealed diffuse increased uptake in the lung and no abnormal uptake in the muscular distribution. Bronchoscopy and biopsy confirmed inflammatory reactions with infiltration by eosinophils, mast cells, and lymphocytes. CT scan showed an interstitial alveolar pattern without fibrosis. EMG demonstrated diffuse myopathy. Muscle biopsy from the right thigh showed an inflammatory myositis with eosinophilic and lymphocytic infiltrations

N-13 L-glutamate uptake in malignancy: its relationship to blood flow

International Nuclear Information System (INIS)

Knapp, W.H.; Helus, F.; Sinn, H.; Ostertag, H.; Georgi, P.; Brandeis, W.E.; Braun, A.

1984-01-01

Studies on glutamate uptake, with special reference to perfusion, were carried out in 35 rats, each bearing one of five different tumor transplants; also in 15 rats after bone fracture, and in three rabbits. Single-pass extraction of N-13 glutamate was 85-93% in the VX2 tumor of the rabbit and in muscle. Bone fracture in rats caused a threefold increase of tracer uptake 2 days after the event. Comparing N-13 glutamate uptake with the retention of 1-121 microspheres, identical tumor-to-muscle ratios were found for three out of five tumor lines. Comparing the uptake with that of C-11 butanol (ten rats), a close correlation was observed throughout the range of tumor lines. The results suggested that glutamate uptake by malignant tumors is related to blood flow. In nine patients with malignant or benign lesions tumor-to-muscle uptake of N-13 glutamate and Tl-201 showed a linear correlation close to identity

Distribution of skeletal muscle involvement in autosomal recessive distal muscular dystrophy. A clinical and computed tomographic study

Energy Technology Data Exchange (ETDEWEB)

Mizusawa, Hidehiro; Nakanishi, Takao; Kobayashi, Fumie

1987-02-01

Distribution of skeletal muscle involvement in 5 cases with autosomal recessive distal muscular dystrophy was studied clinically and by computed tomography (CT). Manual muscle test showed muscle involvement with a predilection for flexors in the lower leg and adductors in the thigh. Flexion and extension of the thigh and the lower leg was impaired to similar degree. In progressed cases, neck flexors and trunk muscles were also affected mildly. CT disclosed more clearly the preferential involvement of flexors in the lower leg, and involvement of both hamstrings center dot adductors group and extensors group of the thigh to similar degree. However, m. popliteus was curiously well preserved. In addition, there was a stage showing high density and hypertrophy of m. sartorius, m. gracilis, m. adductor, m. biceps femoris, m. semimenbranosus, m. semitendinosus or m. rectus femoris, which in thought to be compensatory hypertrophy. M. gluteus minimus in the pelvic girdle and m. dorsi proprii in the trunk were also liable to be affected. The CT findings are regarded as characteristic features noted clearly before muscle weakness and atrophy become apparent clinically. CT is very useful for distinguishing distal muscular dystrophy from rimmed vacuolar distal myopathy in which m. quadriceps femoris and flexors of the lower leg are usually well preserved without compensatory hypertrophy on CT.

Nur77 coordinately regulates expression of genes linked to glucose metabolism in skeletal muscle.

Science.gov (United States)

Chao, Lily C; Zhang, Zidong; Pei, Liming; Saito, Tsugumichi; Tontonoz, Peter; Pilch, Paul F

2007-09-01

Innervation is important for normal metabolism in skeletal muscle, including insulin-sensitive glucose uptake. However, the transcription factors that transduce signals from the neuromuscular junction to the nucleus and affect changes in metabolic gene expression are not well defined. We demonstrate here that the orphan nuclear receptor Nur77 is a regulator of gene expression linked to glucose utilization in muscle. In vivo, Nur77 is preferentially expressed in glycolytic compared with oxidative muscle and is responsive to beta-adrenergic stimulation. Denervation of rat muscle compromises expression of Nur77 in parallel with that of numerous genes linked to glucose metabolism, including glucose transporter 4 and genes involved in glycolysis, glycogenolysis, and the glycerophosphate shuttle. Ectopic expression of Nur77, either in rat muscle or in C2C12 muscle cells, induces expression of a highly overlapping set of genes, including glucose transporter 4, muscle phosphofructokinase, and glycogen phosphorylase. Furthermore, selective knockdown of Nur77 in rat muscle by small hairpin RNA or genetic deletion of Nur77 in mice reduces the expression of a battery of genes involved in skeletal muscle glucose utilization in vivo. Finally, we show that Nur77 binds the promoter regions of multiple genes involved in glucose metabolism in muscle. These results identify Nur77 as a potential mediator of neuromuscular signaling in the control of metabolic gene expression.

Rates and tissue sites of non-insulin- and insulin-mediated glucose uptake in humans

International Nuclear Information System (INIS)

Baron, A.D.; Brechtel, G.; Wallace, P.; Edelman, S.V.

1988-01-01

In vivo glucose uptake can occur via two mechanisms, namely, insulin-mediated glucose uptake (IMGU) and non-insulin-mediated glucose uptake (NIMGU). Although the principal tissue sites for IMGU are skeletal muscle, the tissue sites for NIMGU at a given serum glucose concentration are not known. To examine this issue, rates of whole body glucose uptake (Rd) were measured at basal and during glucose clamp studies performed at euglycemia (approximately 90 mg/dl) and hyperglycemia (approximately 220 mg/dl) in six lean healthy men. Studies were performed during hyperinsulinemia (approximately 70 microU/ml) and during somatostatin-induced insulinopenia to measure IMGU and NIMGU, respectively. During each study, leg glucose balance (arteriovenous catheter technique) was also measured. With this approach, rates of whole body skeletal muscle IMGU and NIMGU can be estimated, and the difference between overall Rd and skeletal muscle glucose uptake represents non-skeletal muscle Rd. The results indicate that approximately 20% of basal Rd is into skeletal muscle. During insulinopenia approximately 86% of body NIMGU occurs in non-skeletal muscle tissues at euglycemia. When hyperglycemia was created, whole body NIMGU increased from 128 +/- 6 to 213 +/- 18 mg/min (P less than 0.01); NIMGU into non-skeletal muscle tissues was 134 +/- 11 and 111 +/- 6 mg/min at hyperglycemia and euglycemia, respectively, P = NS. Therefore, virtually all the hyperglycemia induced increment in NIMGU occurred in skeletal muscle. During hyperinsulinemia, IMGU in skeletal muscle represented 75 and 95% of body Rd, at euglycemia and hyperglycemia, respectively

THE CONTRIBUTION OF 'RESTING' BODY MUSCLES TO THE SLOW COMPONENT OF PULMONARY OXYGEN UPTAKE DURING HIGH-INTENSITY CYCLING

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Susan A. Ward

2012-12-01

Full Text Available Oxygen uptake (VO2 kinetics during moderate constant- workrate (WR exercise (>lactate-threshold (ӨL are well described as exponential. AboveӨL, these kinetics are more complex, consequent to the development of a delayed slow component (VO2sc, whose aetiology remains controversial. To assess the extent of the contribution to the VO2sc from arm muscles involved in postural stability during cycling, six healthy subjects completed an incremental cycle-ergometer test to the tolerable limit for estimation of ӨL and determination of peak VO2. They then completed two constant-WR tests at 90% of ӨL and two at 80% of ∆ (difference between ӨL and VO2peak. Gas exchange variables were derived breath-by-breath. Local oxygenation profiles of the vastus lateralis and biceps brachii muscles were assessed by near-infrared spectroscopy, with maximal voluntary contractions (MVC of the relevant muscles being performed post-exercise to provide a frame of reference for normalising the exercise-related oxygenation responses across subjects. Above supra-ӨL, VO2 rose in an exponential-like fashion ("phase 2, with a delayed VO2sc subsequently developing. This was accompanied by an increase in [reduced haemoglobin] relative to baseline (∆[Hb], which attained 79 ± 13 % (mean, SD of MVC maximum in vastus lateralis at end-exercise and 52 ± 27 % in biceps brachii. Biceps brachii ∆[Hb] was significantly correlated with VO2 throughout the slow phase. In contrast, for sub- L exercise, VO2 rose exponentially to reach a steady state with a more modest increase in vastus lateralis ∆[Hb] (30 ± 11 %; biceps brachii ∆[Hb] was minimally affected (8 ± 2 %. That the intramuscular O2 desaturation profile in biceps brachii was proportional to that for VO2sc during supra-ӨL cycle ergometry is consistent with additional stabilizing arm work contributing to the VO2sc

Localization of dystonic muscles using {sup 18}F-FDG PET/CT in idiopathic cervical dystonia

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Choi, J. Y.; Seung, D. H.; Kim, D. H.; Kim, E. S.; Sohn, Y. I.; Choi, Y.; Choi, E. S.; Lee, K. H.; Kim, B. T. [Samsung Medical Center, Seoul (Korea, Republic of)

2007-07-01

Chemodenervation with botulinum toxin (BT) is regarded as a first-line treatment for idiopathic cervical dystonia (ICD), sometimes referred to as spasmodic torticollis. Moreover, because effective treatment involves the injection of BT into most dystonic muscles, the accurate localization of dystonic muscles is clinically important. In this preliminary study, we investigated whether {sup 18}F-FDG PET/CT is useful for localizing dystonic cervical muscles in ICD by comparing disease severity after and before BT injection into muscles determined to be hypermetabolic by PET/CT. Six consecutive patients (all males; age 37 16 y) underwent {sup 18}F-FDG PET/CT once (n = 4) or twice (n = 2) in a supine (n = 5) or sitting position (n = 3) during the {sup 18}F-FDG uptake period. Dystonic muscles suitable for BT injection therapy were defined as those showing diffusely increased {sup 18}F-FDG uptake. To evaluate response to BT injection, the Tsui scale and the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) were applied. On PET/CT, hypermetabolic cervical muscles were identified in all 6 patients (3 in a supine position and 3 in a sitting position during {sup 18}F-FDG uptake periods). In 2 patients who underwent PET/CT in a supine and in a sitting position during 18F-FDG uptake, abnormal hypermetabolic muscles were observed only by PET/CT in a sitting position with patients heads and necks in the assumed abnormal involuntary posture. Symptoms were significantly improved, according to the Tsui (10.0 2.9 to 1.8 1.3, 82% reduction) and TWSTRS scales (severity: 21.3 2.1 to 5.8 5.3, 73% reduction; disability: 19.8 1.9 to 3.8 3.8, 81 % reduction) in all 4 patients who underwent BT injection therapy guided by PET/CT and who were clinically follow-up. {sup 18}F-FDG PET/CT is potentially useful for identifying dystonic cervical muscles in patients with ICD.

Protein S-glutathionylation lowers superoxide/hydrogen peroxide release from skeletal muscle mitochondria through modification of complex I and inhibition of pyruvate uptake.

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Robert M Gill

Full Text Available Protein S-glutathionylation is a reversible redox modification that regulates mitochondrial metabolism and reactive oxygen species (ROS production in liver and cardiac tissue. However, whether or not it controls ROS release from skeletal muscle mitochondria has not been explored. In the present study, we examined if chemically-induced protein S-glutathionylation could alter superoxide (O2●-/hydrogen peroxide (H2O2 release from isolated muscle mitochondria. Disulfiram, a powerful chemical S-glutathionylation catalyst, was used to S-glutathionylate mitochondrial proteins and ascertain if it can alter ROS production. It was found that O2●-/H2O2 release rates from permeabilized muscle mitochondria decreased with increasing doses of disulfiram (100-500 μM. This effect was highest in mitochondria oxidizing succinate or palmitoyl-carnitine, where a ~80-90% decrease in the rate of ROS release was observed. Similar effects were detected in intact mitochondria respiring under state 4 conditions. Incubation of disulfiram-treated mitochondria with DTT (2 mM restored ROS release confirming that these effects were associated with protein S-glutathionylation. Disulfiram treatment also inhibited phosphorylating and proton leak-dependent respiration. Radiolabelled substrate uptake experiments demonstrated that disulfiram inhibited pyruvate import but had no effect on carnitine uptake. Immunoblot analysis of complex I revealed that it contained several protein S-glutathionylation targets including NDUSF1, a subunit required for NADH oxidation. Taken together, these results demonstrate that O2●-/H2O2 release from muscle mitochondria can be altered by protein S-glutathionylation. We attribute these changes to the protein S-glutathionylation complex I and inhibition of mitochondrial pyruvate carrier.

Involvement of the Interosseous and Lumbrical Muscle-Tendon Units in the Lateral and Spiral Cords in Dupuytren's Disease of the Middle Fingers.

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Thoma, Achilleas; Karpinski, Marta

2017-07-01

The nature of intrinsic muscle involvement in Dupuytren's disease of the middle fingers (long and ring) remains poorly characterized. Over the years, the authors have observed that both the spiral and lateral digital cords in the middle fingers receive contribution from intrinsic muscle-tendon units. This report describes the anatomical characteristics and frequency of intrinsic muscle-tendon unit involvement in Dupuytren's disease of the middle fingers. Intrinsic muscle involvement in the middle digits was recorded in the operative reports of patients undergoing Dupuytren's surgery between October of 2013 and February of 2016. The anatomical variations of diseased fascia were delineated and classified. Of the 113 digits with Dupuytren's contracture operated on during this period, 52 involved the middle fingers (12 long and 40 ring fingers). Intrinsic muscles were found to be involved in the contracture of 14 of these digits. Two unique contracture patterns were identified: type I contracture, which involves a lateral digital cord originating from intrinsic muscle-tendon units and contracting only the proximal interphalangeal joint; and type II contracture, which involves a spiral cord receiving contribution from intrinsic muscle-tendon units and contracting both the metacarpophalangeal and proximal interphalangeal joints. The frequency of type I and type II contractures was 6 percent and 12 percent, respectively. Intrinsic hand muscles may contribute to Dupuytren's disease in the middle digits, and the authors suggest resecting cords as close as possible to their musculotendinous origin to improve postoperative outcomes.

Effects of long-term football training on the expression profile of genes involved in muscle oxidative metabolism

DEFF Research Database (Denmark)

Alfieri, A; Martone, D; Randers, Morten Bredsgaard

2015-01-01

and a muscle biopsy from the vastus lateralis were collected at T0 (pre intervention) and at T1 (post intervention). Gene expression was measured by RTqPCR on RNA extracted from muscle biopsies. The expression levels of the genes principally involved in energy metabolism (PPARγ, adiponectin, AMPKα1/α2, TFAM...... to improve the expression of muscle molecular biomarkers that are correlated to oxidative metabolism in healthy males....... are directly or indirectly involved in the glucose and lipid oxidative metabolism. Multiple linear regression analysis revealed that fat percentage was independently associated with NAMPT, PPARγ and adiponectin expression. In conclusion, long-term recreational football training could be a useful tool...

Symmetric increased skeletal muscular uptake of 18F fluoro-deoxyglucose: a clue for the diagnosis of Graves' disease

International Nuclear Information System (INIS)

Santhosh, Sampath; Mittal, Bhagwant Rai; Kashyap, Raghava; Bhattacharya, Anish; Singh, Baljinder

2011-01-01

18 F fluoro-deoxyglucose (FDG) uptake in the thyroid and thymus is well reported in patients with Grave's disease. Incidental skeletal muscle uptake has also been reported in other non-musculoskeletal (benign and malignant) pathologies. We report a patient of Grave's disease showing symmetrical skeletal muscle uptake but no thyroidal or thymus uptake of FDG. (author)

14(R,S)-[18F]Fluoro-6-thia-heptadecanoic acid as a tracer of free fatty acid uptake and oxidation in myocardium and skeletal muscle

International Nuclear Information System (INIS)

Takala, Teemu O.; Nuutila, Pirjo; Pulkki, Kari; Oikonen, Vesa; Groenroos, Tove; Bergman, Joergen; Forsback, Sarita; Knuuti, Juhani; Savunen, Timo; Vaehaesilta, Tommi; Luotolahti, Matti; Kallajoki, Markku

2002-01-01

14(R,S)-[ 18 F]Fluoro-6-thia-heptadecanoic acid ([ 18 F]FTHA) is a long-chain fatty acid substrate for fatty acid metabolism. [ 18 F]FTHA has been used to study fatty acid metabolism in human heart and skeletal muscle. It has been suggested that the rate of radioactivity accumulation in the myocardium reflects the beta-oxidation rate of free fatty acids (FFAs). However, the net accumulation of FFAs in tissue always represents the sum of FFA oxidation and incorporation into triglycerides. The fraction of [ 18 F]FTHA entering directly into mitochondria for oxidation has not been previously measured. Eight anaesthetized pigs were studied with [ 18 F]FTHA and positron emission tomography (PET). Immediately after each PET experiment, tissue samples from myocardium and skeletal muscle were taken for the isolation of mitochondria and measurements of radioactivity accumulation, and for intracellular [ 18 F]FTHA metabolite analysis. Fractional [ 18 F]FTHA uptake rates were calculated both by graphical analysis of PET data and by measuring 18 F in the tissue samples. Fractional [ 18 F]FTHA uptake rates based on the analysis of tissue samples were 0.56±0.17 ml g -1 min -1 and 0.037±0.007 ml g -1 min -1 for myocardium and skeletal muscle (mean ± SD), respectively. The myocardial results obtained from the PET data (0.50±0.11 ml g -1 min -1 ) were similar to the values obtained from the tissue samples (r=0.94, P=0.002). We also found that 89%±23% (mean±SD, n=7) of the 18 F entered mitochondria in myocardium, as compared with only 36%±15% (mean±SD, n=7) in skeletal muscle. Intracellular [ 18 F]FTHA metabolite analysis showed that a major part of [ 18 F]FTHA is metabolized in the mitochondria in the heart. Our data suggest that 89% of [ 18 F]FTHA taken up by the heart enters mitochondria. This supports the hypothesis that [ 18 F]FTHA traces FFA beta-oxidation in the heart. In contrast to this, only 36% of [ 18 F]FTHA accumulated in skeletal muscle appears to directly enter

AMP-activated protein kinase in contraction regulation of skeletal muscle metabolism: necessary and/or sufficient?

DEFF Research Database (Denmark)

Jensen, Thomas Elbenhardt; Wojtaszewski, Jørgen; Richter, Erik

2009-01-01

In skeletal muscle, the contraction-activated heterotrimeric 5'-AMP-activated protein kinase (AMPK) protein is proposed to regulate the balance between anabolic and catabolic processes by increasing substrate uptake and turnover in addition to regulating the transcription of proteins involved...... in mitochondrial biogenesis and other aspects of promoting an oxidative muscle phenotype. Here, the current knowledge on the expression of AMPK subunits in human quadriceps muscle and evidence from rodent studies suggesting distinct AMPK subunit expression pattern in different muscle types is reviewed. Then......, the intensity and time dependence of AMPK activation in human quadriceps and rodent muscle are evaluated. Subsequently, a major part of this review critically examines the evidence supporting a necessary and/or sufficient role of AMPK in a broad spectrum of skeletal muscle contraction-relevant processes...

The uptake of radioactive phosphorus by brown trout (Salmo trutta L.) from water and food

International Nuclear Information System (INIS)

Winpenny, K.; Knowles, J.F.; Smith, D.L.

1998-01-01

Brown trout were exposed to 32 P in their tank water (7.4 Bq l -1 ) and the uptake to muscle followed over 6 weeks. A steady-state concentration factor (C ss ) of 1.7 and a biological half-time for clearance (tb1/2)) of 45 days were calculated from the results. The low C ss ) indicates that uptake from water is not a major route of 32 P accumulation in these fish. Brown trout were given a single 32 P-spiked meal, and the uptake and clearance in muscle, liver and blood followed over 6 weeks. Assimilation of the isotope by these organs was low, the maximum activity in whole muscle reaching only 0.2-0.4% of that in the meal with lower values in the other two organs. There was no appreciable clearance of 32 P from muscle during the experiment. The slow clearance of 32 P after uptake from water and lack of any clearance after uptake from food indicates that the C ss for this isotope following uptake by either route is likely to depend on radioactive decay rather than intake rate and physiological clearance. (author)

Waldenstrom macroglobulinemia involving the superior rectus muscle

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J.B. Hellman

2018-06-01

Full Text Available Purpose: We present the first reported case of Waldenstrom macroglobulinemia in the right superior rectus causing diplopia. Observations: A 72-year-old man with a 6-month history of untreated asymptomatic Waldenstrom macroglobulinemia presented with 2 years of diagonal binocular diplopia that was previously thought to be due to ocular myasthenia gravis. Examination showed mild right proptosis and right hypotropia, and MRI revealed a focal lesion of the right superior rectus muscle. Orbital biopsy was performed, and histopathology showed lymphoplasmacytic infiltration among the skeletal muscle fibers of the rectus muscle. Immunostaining confirmed a B-cell preponderance, along with more extensive staining for IgM than IgG, and in situ hybridization confirmed lambda restriction. These findings corresponded with those of his previous bone marrow biopsy, confirming Waldenstrom macroglobulinemia as the etiology for the extraocular muscle mass. Conclusions and Importance: Lymphoma of an extraocular muscle is a rare manifestation of orbital lymphoma, and the tumors are usually mucosa-associated lymphoid tissue (MALT lymphomas (i.e. extranodal marginal zone lymphomas. There are 4 previous reports of lymphoplasmacytic lymphoma of an extraocular muscle; however this is the first reported case of such a lesion in a patient with concurrent Waldenstrom macroglobulinemia at the time of diagnosis. Keywords: Waldenstrom's macroglobulinemia, Lymphoma, Superior rectus, Diplopia

Alpha and beta adrenergic effects on metabolism in contracting, perfused muscle

DEFF Research Database (Denmark)

Richter, Erik; Ruderman, N B; Galbo, H

1982-01-01

The role of alpha- and beta-adrenergic receptor stimulation for the effect of epinephrine on muscle glycogenolysis, glucose- and oxygen uptake and muscle performance was studied in the perfused rat hindquarter at rest and during electrical stimulation (60 contractions/min). Adrenergic stimulation...... was obtained by epinephrine in a physiological concentration (2.4 X 10(-8) M) and alpha- and beta-adrenergic blockade by 10(-5) M phentolamine and propranolol, respectively. Epinephrine enhanced net glycogenolysis during contractions most markedly in slow-twitch red fibers. In these fibers the effect...... was mediated by alpha- as well as by beta-adrenergic stimulation, the latter involving production of cAMP, phosphorylase activation and synthase inactivation. In contrast, in fast-twitch fibers only beta-adrenergic mechanisms were involved in the glycogenolytic effect of epinephrine. Moreover, inactivation...

Mitochondria in the Aging Muscles of Flies and Mice: New Perspectives for Old Characters

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Andrea del Campo

2016-01-01

Full Text Available Sarcopenia is the loss of muscle mass accompanied by a decrease in muscle strength and resistance and is the main cause of disability among the elderly. Muscle loss begins long before there is any clear physical impact in the senior adult. Despite all this, the molecular mechanisms underlying muscle aging are far from being understood. Recent studies have identified that not only mitochondrial metabolic dysfunction but also mitochondrial dynamics and mitochondrial calcium uptake could be involved in the degeneration of skeletal muscle mass. Mitochondrial homeostasis influences muscle quality which, in turn, could play a triggering role in signaling of systemic aging. Thus, it has become apparent that mitochondrial status in muscle cells could be a driver of whole body physiology and organismal aging. In the present review, we discuss the existing evidence for the mitochondria related mechanisms underlying the appearance of muscle aging and sarcopenia in flies and mice.

Visualization of multiple organ amyloid involvement in systemic amyloidosis using {sup 11}C-PiB PET imaging

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Ezawa, Naoki; Katoh, Nagaaki; Yoshinaga, Tsuneaki [Shinshu University School of Medicine, Department of Medicine (Neurology and Rheumatology), Nagano (Japan); Oguchi, Kazuhiro [Jisenkai Brain Imaging Research Center, Matsumoto (Japan); Yazaki, Masahide [Shinshu University School of Health Sciences, Department of Biomedical Laboratory Sciences, Matsumoto (Japan); Shinshu University, Institute for Biomedical Sciences, Matsumoto (Japan); Sekijima, Yoshiki [Shinshu University School of Medicine, Department of Medicine (Neurology and Rheumatology), Nagano (Japan); Jisenkai Brain Imaging Research Center, Matsumoto (Japan); Shinshu University, Institute for Biomedical Sciences, Matsumoto (Japan)

2018-03-15

To investigate the utility of Pittsburgh compound B (PiB) positron emission tomography (PET) imaging for evaluating whole-body amyloid involvement in patients with systemic amyloidosis. Whole-body {sup 11}C-PiB PET was performed in seven patients with systemic immunoglobulin light-chain (AL) amyloidosis, seven patients with hereditary transthyretin (ATTRm) amyloidosis, one asymptomatic TTR mutation carrier and three healthy controls. The correlations between clinical organ involvement, radiological {sup 11}C-PiB uptake and histopathological findings were analysed for each organ. Organ involvement on {sup 11}C-PiB PET imaging showed good correlations with the clinical findings for the heart and stomach. Abnormal tracer uptake was also observed in the spleen, lachrymal gland, submandibular gland, sublingual gland, lymph node, brain, scalp, extraocular muscles, nasal mucosa, pharynx, tongue and nuchal muscles, most of which were asymptomatic. Physiological tracer uptake was universally observed in the urinary tract (kidney, renal pelvis, ureter and bladder) and enterohepatic circulatory system (liver, gallbladder, bile duct and small intestine) in all participants. Most of the patients and one healthy control subject showed asymptomatic tracer uptake in the lung and parotid gland. The peripheral nervous system did not show any tracer uptake even in patients with apparent peripheral neuropathy. Histological amyloid deposition was confirmed in biopsied myocardium and gastric mucosa where abnormal {sup 11}C-PiB retention was observed. {sup 11}C-PiB PET imaging can be used clinically in the systemic evaluation of amyloid distribution in patients with AL and ATTRm amyloidosis. Quantitative analysis of {sup 11}C-PiB PET images may be useful in therapy evaluation and will reveal whether amyloid clearance is correlated with clinical response. (orig.)

Skeletal muscle O-GlcNAc transferase is important for muscle energy homeostasis and whole-body insulin sensitivity.

Science.gov (United States)

Shi, Hao; Munk, Alexander; Nielsen, Thomas S; Daughtry, Morgan R; Larsson, Louise; Li, Shize; Høyer, Kasper F; Geisler, Hannah W; Sulek, Karolina; Kjøbsted, Rasmus; Fisher, Taylor; Andersen, Marianne M; Shen, Zhengxing; Hansen, Ulrik K; England, Eric M; Cheng, Zhiyong; Højlund, Kurt; Wojtaszewski, Jørgen F P; Yang, Xiaoyong; Hulver, Matthew W; Helm, Richard F; Treebak, Jonas T; Gerrard, David E

2018-05-01

Given that cellular O-GlcNAcylation levels are thought to be real-time measures of cellular nutrient status and dysregulated O-GlcNAc signaling is associated with insulin resistance, we evaluated the role of O-GlcNAc transferase (OGT), the enzyme that mediates O-GlcNAcylation, in skeletal muscle. We assessed O-GlcNAcylation levels in skeletal muscle from obese, type 2 diabetic people, and we characterized muscle-specific OGT knockout (mKO) mice in metabolic cages and measured energy expenditure and substrate utilization pattern using indirect calorimetry. Whole body insulin sensitivity was assessed using the hyperinsulinemic euglycemic clamp technique and tissue-specific glucose uptake was subsequently evaluated. Tissues were used for histology, qPCR, Western blot, co-immunoprecipitation, and chromatin immunoprecipitation analyses. We found elevated levels of O-GlcNAc-modified proteins in obese, type 2 diabetic people compared with well-matched obese and lean controls. Muscle-specific OGT knockout mice were lean, and whole body energy expenditure and insulin sensitivity were increased in these mice, consistent with enhanced glucose uptake and elevated glycolytic enzyme activities in skeletal muscle. Moreover, enhanced glucose uptake was also observed in white adipose tissue that was browner than that of WT mice. Interestingly, mKO mice had elevated mRNA levels of Il15 in skeletal muscle and increased circulating IL-15 levels. We found that OGT in muscle mediates transcriptional repression of Il15 by O-GlcNAcylating Enhancer of Zeste Homolog 2 (EZH2). Elevated muscle O-GlcNAc levels paralleled insulin resistance and type 2 diabetes in humans. Moreover, OGT-mediated signaling is necessary for proper skeletal muscle metabolism and whole-body energy homeostasis, and our data highlight O-GlcNAcylation as a potential target for ameliorating metabolic disorders. Copyright © 2018 The Authors. Published by Elsevier GmbH.. All rights reserved.

Racl Signaling Is Required for Insulin-Stimulated Glucose Uptake and Is Dysregulated in Insulin-Resistant Murine and Human Skeletal Muscle

DEFF Research Database (Denmark)

Sylow, L.; Jensen, T. E.; Kleinert, M.

2013-01-01

The actin cytoskeleton-regulating GTPase Racl is required for insulin-stimulated GLUT4 translocation in cultured muscle cells. However, involvement of Racl and its downstream signaling in glucose transport in insulin-sensitive and insulin-resistant mature skeletal muscle has not previously been i...

14(R,S)-[{sup 18}F]Fluoro-6-thia-heptadecanoic acid as a tracer of free fatty acid uptake and oxidation in myocardium and skeletal muscle

Energy Technology Data Exchange (ETDEWEB)

Takala, Teemu O.; Nuutila, Pirjo [Turku PET Centre, Turku University Central Hospital, PO Box 52, 20521 Turku (Finland); Department of Medicine, University of Turku (Finland); Pulkki, Kari [Department of Clinical Chemistry, University of Turku (Finland); Oikonen, Vesa; Groenroos, Tove; Bergman, Joergen; Forsback, Sarita; Knuuti, Juhani [Turku PET Centre, Turku University Central Hospital, PO Box 52, 20521 Turku (Finland); Savunen, Timo; Vaehaesilta, Tommi [Department of Surgery, University of Turku (Finland); Luotolahti, Matti [Department of Clinical Physiology, University of Turku (Finland); Kallajoki, Markku [Department of Pathology, University of Turku (Finland)

2002-12-01

14(R,S)-[{sup 18}F]Fluoro-6-thia-heptadecanoic acid ([{sup 18}F]FTHA) is a long-chain fatty acid substrate for fatty acid metabolism. [{sup 18}F]FTHA has been used to study fatty acid metabolism in human heart and skeletal muscle. It has been suggested that the rate of radioactivity accumulation in the myocardium reflects the beta-oxidation rate of free fatty acids (FFAs). However, the net accumulation of FFAs in tissue always represents the sum of FFA oxidation and incorporation into triglycerides. The fraction of [{sup 18}F]FTHA entering directly into mitochondria for oxidation has not been previously measured. Eight anaesthetized pigs were studied with [{sup 18}F]FTHA and positron emission tomography (PET). Immediately after each PET experiment, tissue samples from myocardium and skeletal muscle were taken for the isolation of mitochondria and measurements of radioactivity accumulation, and for intracellular [{sup 18}F]FTHA metabolite analysis. Fractional [{sup 18}F]FTHA uptake rates were calculated both by graphical analysis of PET data and by measuring {sup 18}F in the tissue samples. Fractional [{sup 18}F]FTHA uptake rates based on the analysis of tissue samples were 0.56{+-}0.17 ml g{sup -1} min{sup -1} and 0.037{+-}0.007 ml g{sup -1} min{sup -1} for myocardium and skeletal muscle (mean {+-} SD), respectively. The myocardial results obtained from the PET data (0.50{+-}0.11 ml g{sup -1} min{sup -1}) were similar to the values obtained from the tissue samples (r=0.94, P=0.002). We also found that 89%{+-}23% (mean{+-}SD, n=7) of the {sup 18}F entered mitochondria in myocardium, as compared with only 36%{+-}15% (mean{+-}SD, n=7) in skeletal muscle. Intracellular [{sup 18}F]FTHA metabolite analysis showed that a major part of [{sup 18}F]FTHA is metabolized in the mitochondria in the heart. Our data suggest that 89% of [{sup 18}F]FTHA taken up by the heart enters mitochondria. This supports the hypothesis that [{sup 18}F]FTHA traces FFA beta-oxidation in the heart

Physiological background of the change point in VO2 and the slow component of oxygen uptake kinetics.

Science.gov (United States)

Zoładź, J A; Korzeniewski, B

2001-06-01

It is generally believed that oxygen uptake during incremental exercise--until VO2max, increases linearly with power output (see eg. Astrand & Rodahl, 1986). On the other hand, it is well established that the oxygen uptake reaches a steady state only during a low power output exercise, but during a high power output exercise, performed above the lactate threshold (LT), the oxygen uptake shows a continuous increase until the end of the exercise. This effect has been called the slow component of VO2 kinetics (Whipp & Wasserman, 1972). The presence of a slow component in VO2 kinetics implies that during an incremental exercise test, after the LT has been exceeded, the VO2 to power output relationship has to become curvilinear. Indeed, it has recently been shown that during the incremental exercise, the exceeding of the power output, at which blood lactate begins to accumulate (LT), causes a non-proportional increase in VO2 (Zoladz et al. 1995) which indicates a drop in muscle mechanical efficiency. The power output at which VO2 starts to rise non-proportionally to the power output has been called "the change point in VO2" (Zoladz et al. 1998). In this paper, the significance of the factors most likely involved in the physiological mechanism responsible for the change point in oxygen uptake (CP-VO2) and for the slow component of VO2 kinetics, including: increase of activation of additional muscle groups, intensification of the respiratory muscle activity, recruitment of type II muscle fibres, increase of muscle temperature, increase of the basal metabolic rate, lactate and hydrogen ion accumulation, proton leak through the inner mitochondrial membrane, slipping of the ATP synthase and a decrease in the cytosolic phosphorylation potential, are discussed. Finally, an original own model describing the sequence of events leading to the non-proportional increase of oxygen cost of work at a high exercise intensity is presented.

Studies on the uptake of 14C-neostigmine in the isolated rat diaphragm

International Nuclear Information System (INIS)

Helleberg, L.

1976-01-01

The uptake process of 14 C-neostigmine in striated muscles was studied using the isolated rat diaphragm. Hemidiaphragms were incubated with 3x10 -7 M 14 C-neostigmine at 37deg in Krebs-Ringer solution containing 11 mM glucose and aerated with oxygen:carbon dioxide (95:5 v/v %). The uptake, which is expressed as the muscle-to-medium concentration ratio, was 1.41, after 3 hours, after which the rate of uptake diminished and became equal to that of inulin. The uptake which showed partial saturation, was decreased by some tertiary and quarternary amines, metabolic inhibitors, potassium and in an atmosphere of nitrogen. Neostigmine accumulated in all parts of the muscle without preference for the end plate zone. The half-time for the efflux was about 30 min. The phrenic nerve-diaphragm preparation became desensitized to the effect of 3x10 -7 M neostigmine after 2-3 hours. It is suggested that the uptake of neostigmine is mediated via a specialized carrier transport system. (author)

AMP-activated protein kinase plays an important evolutionary conserved role in the regulation of glucose metabolism in fish skeletal muscle cells.

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Leonardo J Magnoni

Full Text Available AMPK, a master metabolic switch, mediates the observed increase of glucose uptake in locomotory muscle of mammals during exercise. AMPK is activated by changes in the intracellular AMP:ATP ratio when ATP consumption is stimulated by contractile activity but also by AICAR and metformin, compounds that increase glucose transport in mammalian muscle cells. However, the possible role of AMPK in the regulation of glucose metabolism in skeletal muscle has not been investigated in other vertebrates, including fish. In this study, we investigated the effects of AMPK activators on glucose uptake, AMPK activity, cell surface levels of trout GLUT4 and expression of GLUT1 and GLUT4 as well as the expression of enzymes regulating glucose disposal and PGC1α in trout myotubes derived from a primary muscle cell culture. We show that AICAR and metformin significantly stimulated glucose uptake (1.6 and 1.3 fold, respectively and that Compound C completely abrogated the stimulatory effects of the AMPK activators on glucose uptake. The combination of insulin and AMPK activators did not result in additive nor synergistic effects on glucose uptake. Moreover, exposure of trout myotubes to AICAR and metformin resulted in an increase in AMPK activity (3.8 and 3 fold, respectively. We also provide evidence suggesting that stimulation of glucose uptake by AMPK activators in trout myotubes may take place, at least in part, by increasing the cell surface and mRNA levels of trout GLUT4. Finally, AICAR increased the mRNA levels of genes involved in glucose disposal (hexokinase, 6-phosphofructokinase, pyruvate kinase and citrate synthase and mitochondrial biogenesis (PGC-1α and did not affect glycogen content or glycogen synthase mRNA levels in trout myotubes. Therefore, we provide evidence, for the first time in non-mammalian vertebrates, suggesting a potentially important role of AMPK in stimulating glucose uptake and utilization in the skeletal muscle of fish.

Lower leg muscle involvement in Duchenne muscular dystrophy: an MR imaging and spectroscopy study

International Nuclear Information System (INIS)

Torriani, Martin; Townsend, Elise; Thomas, Bijoy J.; Bredella, Miriam A.; Ghomi, Reza H.; Tseng, Brian S.

2012-01-01

To describe the involvement of lower leg muscles in boys with Duchenne muscular dystrophy (DMD) by using MR imaging (MRI) and spectroscopy (MRS) correlated to indices of functional status. Nine boys with DMD (mean age, 11 years) and eight healthy age- and BMI-matched boys (mean age, 13 years) prospectively underwent lower leg MRI, 1H-MRS of tibialis anterior (TA) and soleus (SOL) for lipid fraction measures, and 31P-MRS for pH and high-energy phosphate measures. DMD subjects were evaluated using the Vignos lower extremity functional rating, and tests including 6 min walk test (6MWT) and 10 m walk. DMD subjects had highest fatty infiltration scores in peroneal muscles, followed by medial gastrocnemius and soleus. Compared to controls, DMD boys showed higher intramuscular fat (P = 0.04), lipid fractions of TA and SOL (P = 0.02 and 0.003, respectively), pH of anterior compartment (P = 0.0003), and lower phosphocreatine/inorganic phosphorus ratio of posterior compartment (P = 0.02). The Vignos rating correlated with TA (r = 0.79, P = 0.01) and SOL (r = 0.71, P = 0.03) lipid fractions. The 6MWT correlated with fatty infiltration scores of SOL (r = -0.76, P = 0.046), medial (r = -0.80, P = 0.03) and lateral (r = -0.84, P = 0.02) gastrocnemius, intramuscular fat (r = -0.80, P = 0.03), and SOL lipid fraction (r = -0.89, P = 0.007). Time to walk 10 m correlated with anterior compartment pH (r = 0.78, P = 0.04). Lower leg muscles of boys with DMD show a distinct involvement pattern and increased adiposity that correlates with functional status. Lower leg MRI and 1H-MRS studies may help to noninvasively demonstrate the severity of muscle involvement. (orig.)

Lower leg muscle involvement in Duchenne muscular dystrophy: an MR imaging and spectroscopy study

Energy Technology Data Exchange (ETDEWEB)

Torriani, Martin [Massachusetts General Hospital and Harvard Medical School, Division of Musculoskeletal Imaging and Intervention, Boston, MA (United States); Massachusetts General Hospital, Musculoskeletal Imaging and Intervention, Department of Radiology, Boston, MA (United States); Townsend, Elise [MGH Institute of Health Professions and Massachusetts General Hospital, Boston, MA (United States); Thomas, Bijoy J.; Bredella, Miriam A.; Ghomi, Reza H. [Massachusetts General Hospital and Harvard Medical School, Division of Musculoskeletal Imaging and Intervention, Boston, MA (United States); Tseng, Brian S. [Massachusetts General Hospital and Harvard Medical School, Pediatric Neuromuscular Clinic, Boston, MA (United States); Novartis Institute of Biomedical Research, Cambridge, MA (United States)

2012-04-15

To describe the involvement of lower leg muscles in boys with Duchenne muscular dystrophy (DMD) by using MR imaging (MRI) and spectroscopy (MRS) correlated to indices of functional status. Nine boys with DMD (mean age, 11 years) and eight healthy age- and BMI-matched boys (mean age, 13 years) prospectively underwent lower leg MRI, 1H-MRS of tibialis anterior (TA) and soleus (SOL) for lipid fraction measures, and 31P-MRS for pH and high-energy phosphate measures. DMD subjects were evaluated using the Vignos lower extremity functional rating, and tests including 6 min walk test (6MWT) and 10 m walk. DMD subjects had highest fatty infiltration scores in peroneal muscles, followed by medial gastrocnemius and soleus. Compared to controls, DMD boys showed higher intramuscular fat (P = 0.04), lipid fractions of TA and SOL (P = 0.02 and 0.003, respectively), pH of anterior compartment (P = 0.0003), and lower phosphocreatine/inorganic phosphorus ratio of posterior compartment (P = 0.02). The Vignos rating correlated with TA (r = 0.79, P = 0.01) and SOL (r = 0.71, P = 0.03) lipid fractions. The 6MWT correlated with fatty infiltration scores of SOL (r = -0.76, P = 0.046), medial (r = -0.80, P = 0.03) and lateral (r = -0.84, P = 0.02) gastrocnemius, intramuscular fat (r = -0.80, P = 0.03), and SOL lipid fraction (r = -0.89, P = 0.007). Time to walk 10 m correlated with anterior compartment pH (r = 0.78, P = 0.04). Lower leg muscles of boys with DMD show a distinct involvement pattern and increased adiposity that correlates with functional status. Lower leg MRI and 1H-MRS studies may help to noninvasively demonstrate the severity of muscle involvement. (orig.)

Characteristic of muscle involvement evaluated by CT scans in early stages of progressive muscular dystrophy; Comparison between Duchenne and Fukuyama types

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Arai, Yumi (Tokyo Women' s Medical Coll. (Japan))

1993-10-01

Muscle CT scans were performed in order to compare the characteristic distribution of progressive muscle involvement in the early stages of Duchenne type (DMD) and Fukuyama type muscular dystrophy (FCMD). Muscle images at the levels of the 3rd lumbar vertebra, thigh and calf were assessed by visual inspection, and mean CT numbers calculated for individual muscles were statistically analysed. On visual inspection, intramuscular low density areas and muscular atrophy were observed in the muscles of older patients with either disease. These changes were, however, more extensive at thigh level in DMD, and at calf level in FCMD. Nevertheless, the mean CT numbers of muscles in which only slight changes were grossly visible on CT scans displayed progressive decreases with increasing age. Moreover, a significant negative relationship was recognizable between age and mean CT number in almost all muscles examined. Comparison of the slopes of the regression lines revealed that the so-called selective pattern of muscle involvement characteristic of the symptomatic stage had already partially manifested in the preclinical or early stages of both diseases. In FCMD, the rates of decrease in CT numbers were extremely rapid for calf muscles as compared with those in DMD, indicating that this is one reason for FCMD patients never becoming ambulatory. However, for almost all of the other muscles, the CT numbers in FCMD decreased in parallel with the corresponding CT numbers in DMD; thus, these diseases displayed a similarity in the pattern of muscle involvement, despite their different pathogenetic mechanisms and inheritance patterns. (author).

Uptake of technetium from seawater by red abalone Haliotis rufescens

International Nuclear Information System (INIS)

Spies, R.B.

1975-01-01

Technetium accumulation from seawater by the abalone Haliotis rufescens was studied with 95 Tc. Concentration factors, uptake rates, steady state concentrations, and biological half-lives were determined experimentally for whole-body uptake. Whole-body concentration factors ranged from 135 to 205; biological half-life was 60 days. Changes in concentration factors were determined for six tissues during the uptake period. The highest activities were in the order of: digestive gland>gill>kidneys>heart>gonad>columnar muscle. Dead shells accumulated little activity compared to shells of living abalone. Gills and digestive system appear to be the routes of entry. Autoradiography shows that of the muscular tissues the outer edge of the foot and epipodium are the most active and the edible columnar muscle the least active. (author)

Mechanosensitive molecular networks involved in transducing resistance exercise-signals into muscle protein accretion

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Emil Rindom

2016-11-01

Full Text Available Loss of skeletal muscle myofibrillar protein with disease and/or inactivity can severely deteriorate muscle strength and function. Strategies to counteract wasting of muscle myofibrillar protein are therefore desirable and invite for considerations on the potential superiority of specific modes of resistance exercise and/or the adequacy of low load resistance exercise regimens as well as underlying mechanisms. In this regard, delineation of the potentially mechanosensitive molecular mechanisms underlying muscle protein synthesis (MPS, may contribute to understanding on how differentiated resistance exercise can transduce a mechanical signal into stimulation of muscle accretion. Recent findings suggest specific upstream exercise-induced mechano-sensitive myocellular signaling pathways to converge on mammalian target of rapamycin complex 1 (mTORC1, to influence MPS. This may e.g. implicate mechanical activation of signaling through a diacylglycerol kinase (DGKζ-phosphatidic acid (PA axis or implicate integrin deformation to signal through a Focal adhesion kinase (FAK-Tuberous Sclerosis Complex 2TSC2-Ras homolog enriched in brain (Rheb axis. Moreover, since initiation of translation is reliant on mRNA, it is also relevant to consider potentially mechanosensitive signaling pathways involved in muscle myofibrillar gene transcription and whether some of these pathways converge with those affecting mTORC1 activation for MPS. In this regard, recent findings suggest how mechanical stress may implicate integrin deformation and/or actin dynamics to signal through a Ras homolog gene family member A protein (RhoA-striated muscle activator of Rho signaling (STARS axis or how it may implicate deformation of Notch to affect Bone Morphogenetic Protein (BMP signaling through a small mother of decapentaplegic (Smad axis.

The TWEAK–Fn14 dyad is involved in age-associated pathological changes in skeletal muscle

International Nuclear Information System (INIS)

Tajrishi, Marjan M.; Sato, Shuichi; Shin, Jonghyun; Zheng, Timothy S.; Burkly, Linda C.; Kumar, Ashok

2014-01-01

Highlights: • The levels of TWEAK receptor Fn14 are increased in skeletal muscle during aging. • Deletion of Fn14 attenuates age-associated skeletal muscle fiber atrophy. • Deletion of Fn14 inhibits proteolysis in skeletal muscle during aging. • TWEAK–Fn14 signaling activates transcription factor NF-κB in aging skeletal muscle. • TWEAK–Fn14 dyad is involved in age-associated fibrosis in skeletal muscle. - Abstract: Progressive loss of skeletal muscle mass and strength (sarcopenia) is a major clinical problem in the elderly. Recently, proinflammatory cytokine TWEAK and its receptor Fn14 were identified as key mediators of muscle wasting in various catabolic states. However, the role of the TWEAK–Fn14 pathway in pathological changes in skeletal muscle during aging remains unknown. In this study, we demonstrate that the levels of Fn14 are increased in skeletal muscle of 18-month old (aged) mice compared with adult mice. Genetic ablation of Fn14 significantly increased the levels of specific muscle proteins and blunted the age-associated fiber atrophy in mice. While gene expression of two prominent muscle-specific E3 ubiquitin ligases MAFBx and MuRF1 remained comparable, levels of ubiquitinated proteins and the expression of autophagy-related molecule Atg12 were significantly reduced in Fn14-knockout (KO) mice compared with wild-type mice during aging. Ablation of Fn14 significantly diminished the DNA-binding activity of transcription factor nuclear factor-kappa B (NF-κB), gene expression of various inflammatory molecules, and interstitial fibrosis in skeletal muscle of aged mice. Collectively, our study suggests that the TWEAK–Fn14 signaling axis contributes to age-associated muscle atrophy and fibrosis potentially through its local activation of proteolytic systems and inflammatory pathways

The TWEAK–Fn14 dyad is involved in age-associated pathological changes in skeletal muscle

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Tajrishi, Marjan M.; Sato, Shuichi; Shin, Jonghyun [Department of Anatomical Sciences and Neurobiology, University of Louisville School of Medicine, Louisville, KY 40202 (United States); Zheng, Timothy S.; Burkly, Linda C. [Department of Immunology, Biogen Idec, 14 Cambridge Center, Cambridge, MA 02142 (United States); Kumar, Ashok [Department of Anatomical Sciences and Neurobiology, University of Louisville School of Medicine, Louisville, KY 40202 (United States)

2014-04-18

Highlights: • The levels of TWEAK receptor Fn14 are increased in skeletal muscle during aging. • Deletion of Fn14 attenuates age-associated skeletal muscle fiber atrophy. • Deletion of Fn14 inhibits proteolysis in skeletal muscle during aging. • TWEAK–Fn14 signaling activates transcription factor NF-κB in aging skeletal muscle. • TWEAK–Fn14 dyad is involved in age-associated fibrosis in skeletal muscle. - Abstract: Progressive loss of skeletal muscle mass and strength (sarcopenia) is a major clinical problem in the elderly. Recently, proinflammatory cytokine TWEAK and its receptor Fn14 were identified as key mediators of muscle wasting in various catabolic states. However, the role of the TWEAK–Fn14 pathway in pathological changes in skeletal muscle during aging remains unknown. In this study, we demonstrate that the levels of Fn14 are increased in skeletal muscle of 18-month old (aged) mice compared with adult mice. Genetic ablation of Fn14 significantly increased the levels of specific muscle proteins and blunted the age-associated fiber atrophy in mice. While gene expression of two prominent muscle-specific E3 ubiquitin ligases MAFBx and MuRF1 remained comparable, levels of ubiquitinated proteins and the expression of autophagy-related molecule Atg12 were significantly reduced in Fn14-knockout (KO) mice compared with wild-type mice during aging. Ablation of Fn14 significantly diminished the DNA-binding activity of transcription factor nuclear factor-kappa B (NF-κB), gene expression of various inflammatory molecules, and interstitial fibrosis in skeletal muscle of aged mice. Collectively, our study suggests that the TWEAK–Fn14 signaling axis contributes to age-associated muscle atrophy and fibrosis potentially through its local activation of proteolytic systems and inflammatory pathways.

Training-induced acceleration of O(2) uptake on-kinetics precedes muscle mitochondrial biogenesis in humans.

Science.gov (United States)

Zoladz, Jerzy A; Grassi, Bruno; Majerczak, Joanna; Szkutnik, Zbigniew; Korostyński, Michał; Karasiński, Janusz; Kilarski, Wincenty; Korzeniewski, Bernard

2013-04-01

The effects of 5 weeks of moderate-intensity endurance training on pulmonary oxygen uptake kinetics (V(O(2)) on-kinetics) were studied in 15 healthy men (mean ± SD: age 22.7 ± 1.8 years, body weight 76.4 ± 8.9 kg and maximal V(O(2)) 46.0 ± 3.7 ml kg(-1) min(-1)). Training caused a significant acceleration (P = 0.003) of V(O(2)) on-kinetics during moderate-intensity cycling (time constant of the 'primary' component 30.0 ± 6.6 versus 22.8 ± 5.6 s before and after training, respectively) and a significant decrease (P = 0.04) in the amplitude of the primary component (837 ± 351 versus 801 ± 330 ml min(-1)). No changes in myosin heavy chain distribution, muscle fibre capillarization, level of peroxisome proliferator-activated receptor γ coactivator 1α and other markers of mitochondrial biogenesis (mitochondrial DNA copy number, cytochrome c and cytochrome oxidase subunit I contents) in the vastus lateralis were found after training. A significant downregulation in the content of the sarcoplasmic reticulum ATPase 2 (SERCA2; P = 0.03) and a tendency towards a decrease in SERCA1 (P = 0.055) was found after training. The decrease in SERCA1 was positively correlated (P = 0.05) with the training-induced decrease in the gain of the V(O(2)) on-kinetics (ΔV(O(2)) at steady state/Δpower output). In the early stage of training, the acceleration in V(O(2)) on-kinetics during moderate-intensity cycling can occur without enhanced mitochondrial biogenesis or changes in muscle myosin heavy chain distribution and in muscle fibre capillarization. The training-induced decrease of the O(2) cost of cycling could be caused by the downregulation of SERCA pumps.

Noninvasive Cu-64-ATSM and PET/CT Assessment of Hypoxia in Rat Skeletal Muscles and Tendons During Muscle Contractions

DEFF Research Database (Denmark)

Skovgaard, D.; Kjaer, M.; Madsen, J.

2009-01-01

the first PET/CT scan. Standardized uptake values (SUVs) were calculated for the Achilles tendons and triceps surae muscles and were correlated to gene expression of HIF1 alpha and CAIII using real-time polymerase chain reaction. Results: Immediately after the contractions, uptake of Cu-64-ATSM......The purpose of the present study was to investigate exercise-related changes in oxygenation in rat skeletal muscles and tendons noninvasively with PET/CT and the hypoxia-selective tracer Cu-64-diacetyl bis(N-4-methylthiosemicarbazone) (ATSM) and to quantitatively study concomitant changes in gene...... expression of 2 hypoxia-related genes, hypoxia-inducible factor 1 alpha (HIF1 alpha) and carbonic anhydrase III (CAIII). Methods: Two groups of Wistar rats performed 1-leg contractions of the calf muscle by electrostimulation of the sciatic nerve. After 10 min of muscle contractions, Cu-64-ATSM was injected...

Noninvasive 64Cu-ATSM and PET/CT Assessment of Hypoxia in Rat Skeletal Muscles and Tendons During Muscle Contractions

DEFF Research Database (Denmark)

Skovgaard, Dorthe; Kjaer, Michael; Madsen, Jacob

2009-01-01

the first PET/CT scan. Standardized uptake values (SUVs) were calculated for the Achilles tendons and triceps surae muscles and were correlated to gene expression of HIF1alpha and CAIII using real-time polymerase chain reaction. RESULTS: Immediately after the contractions, uptake of (64)Cu......The purpose of the present study was to investigate exercise-related changes in oxygenation in rat skeletal muscles and tendons noninvasively with PET/CT and the hypoxia-selective tracer (64)Cu-diacetyl bis(N(4)-methylthiosemicarbazone) (ATSM) and to quantitatively study concomitant changes in gene...... expression of 2 hypoxia-related genes, hypoxia-inducible factor 1alpha (HIF1alpha) and carbonic anhydrase III (CAIII). METHODS: Two groups of Wistar rats performed 1-leg contractions of the calf muscle by electrostimulation of the sciatic nerve. After 10 min of muscle contractions, (64)Cu-ATSM was injected...

Relationship Between the Elevated Muscle FDG Uptake in the Distal Upper Extremities on PET/CT Scan and Prescan Utilization of Mobile Devices in Young Patients.

Science.gov (United States)

Bai, Xia; Wang, Xuemei; Zhuang, Hongming

2018-03-01

It is common to notice increased FDG activity in the muscles of the forearms or hands on PET/CT images. The purpose of this study was to determine relationship between the prevalence of increased FDG activity in the forearms or hands and using mobile devices prior to the FDG PET/CT study. A total of 443 young patients with ages between 5 and 19 years who underwent FDG PET/CT scan were included in this retrospective analysis. All patients had FDG PET/CT with their arms within the field of views. The images were reviewed for elevated activity in the muscles of the distal upper extremities (DUEs), which include forearms and hands. The preimaging questionnaire/interview records regarding using mobile devices prior to FDG PET/CT were also reviewed and compared with the imaging findings. Most patients (72.0% [319/443]) used mobile devices more than 60 minutes in the period of 24 hours prior to the FDG PET/CT study. Elevated uptake in the muscles in the DUEs was observed in 38.6% (123/319) of these patients. In contrast, among 124 patients who did not use the mobile devices or used the mobile device minimally prior to the study, only 6.5% (8/124) of them had elevated FDG activity in the DUEs. The difference persisted following stratification analysis for sex, age, and serum glucose level in our patient population. Increased FDG uptake in the muscles of the DUEs in young patients is commonly seen in those who used mobile devices prior to PET/CT study. Recommendation should be considered to reduce using mobile devices prior to FDG PET/CT study in young patient population.

Skeletal muscle O-GlcNAc transferase is important for muscle energy homeostasis and whole-body insulin sensitivity

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Hao Shi

2018-05-01

Full Text Available Objective: Given that cellular O-GlcNAcylation levels are thought to be real-time measures of cellular nutrient status and dysregulated O-GlcNAc signaling is associated with insulin resistance, we evaluated the role of O-GlcNAc transferase (OGT, the enzyme that mediates O-GlcNAcylation, in skeletal muscle. Methods: We assessed O-GlcNAcylation levels in skeletal muscle from obese, type 2 diabetic people, and we characterized muscle-specific OGT knockout (mKO mice in metabolic cages and measured energy expenditure and substrate utilization pattern using indirect calorimetry. Whole body insulin sensitivity was assessed using the hyperinsulinemic euglycemic clamp technique and tissue-specific glucose uptake was subsequently evaluated. Tissues were used for histology, qPCR, Western blot, co-immunoprecipitation, and chromatin immunoprecipitation analyses. Results: We found elevated levels of O-GlcNAc-modified proteins in obese, type 2 diabetic people compared with well-matched obese and lean controls. Muscle-specific OGT knockout mice were lean, and whole body energy expenditure and insulin sensitivity were increased in these mice, consistent with enhanced glucose uptake and elevated glycolytic enzyme activities in skeletal muscle. Moreover, enhanced glucose uptake was also observed in white adipose tissue that was browner than that of WT mice. Interestingly, mKO mice had elevated mRNA levels of Il15 in skeletal muscle and increased circulating IL-15 levels. We found that OGT in muscle mediates transcriptional repression of Il15 by O-GlcNAcylating Enhancer of Zeste Homolog 2 (EZH2. Conclusions: Elevated muscle O-GlcNAc levels paralleled insulin resistance and type 2 diabetes in humans. Moreover, OGT-mediated signaling is necessary for proper skeletal muscle metabolism and whole-body energy homeostasis, and our data highlight O-GlcNAcylation as a potential target for ameliorating metabolic disorders. Keywords: O-GlcNAc signaling, Type 2 diabetes, N

Identification of a novel phosphorylation site on TBC1D4 regulated by AMP-activated protein kinase in skeletal muscle

DEFF Research Database (Denmark)

Treebak, Jonas Thue; Taylor, Eric B.; Witczak, Carol A.

2010-01-01

TBC1D4 (also known as AS160) regulates GLUT4 translocation and glucose uptake in adipocytes and skeletal muscle. Its mode of action involves phosphorylation of Serine (S)/Threonine (T) residues by upstream kinases resulting in inactivation of Rab-GAP activity leading to GLUT4 mobilization...

Effect of lifelong football training on the expression of muscle molecular markers involved in healthy longevity

DEFF Research Database (Denmark)

Mancini, A; Vitucci, D; Labruna, G

2017-01-01

PURPOSE: We investigated whether lifelong football training affects the expression of healthy longevity-related muscle molecular markers. METHODS: Biopsies were collected from the vastus lateralis muscle of 10 lifelong football-trained men (68.2 ± 3.0 years) and of 10 active untrained healthy men...... the expression of key markers involved in muscle oxidative metabolism, and in the DNA repair and senescence suppression pathways, thus providing the molecular basis for healthy longevity....... (66.7 ± 1.3 years). Gene and protein expression was measured by RTqPCR on RNA and by western blotting on protein extracts from muscle biopsies, respectively. RESULTS: The expression of AMPKα1/α2, NAMPT, TFAM and PGC1α, which are markers of oxidative metabolism, and MyHC β isoform expression was higher...

Myosin heavy chain composition in the vastus lateralis muscle in relation to oxygen uptake and heart rate during cycling in humans.

Science.gov (United States)

Majerczak, J; Nieckarz, Z; Karasinski, J; Zoladz, J A

2014-04-01

In this study we examined the relationship between fast myosin heavy chain (MyHC2) content in the vastus lateralis and the rate of oxygen uptake (VO2) and heart rate (HR) increase during an incremental exercise in 38, young, healthy men. Prior to the exercise test, muscle biopsies were taken in order to evaluate the MyHC composition. It was found that during cycling performed below the lactate threshold (LT), a positive relationship between MyHC2 and the intercept of the oxygen uptake and power output (VO2-PO) relationship existed (r=0.49, P=0.002), despite no correlation between MyHC2 and the slope value of the VO2-PO relationship (r= -0.18, P=0.29). During cycling performed above the LT, MyHC2 correlated positively with the magnitude of the nonlinearity in the VO2-PO relationship; i.e. with the accumulated VO2'excess' (r=0.44, P=0.006) and peak VO2'excess' (r=0.44, P=0.006), as well as with the slope of the HR-PO relationship (r=0.49, P=0.002). We have concluded that a greater MyHC2 content in the vastus lateralis is accompanied by a higher oxygen cost of cycling during exercise performed below the LT. This seems to be related to the higher energy cost of the non-cross-bridge activities in the muscles possessing a greater proportion of MyHC2 content. In the case of heavy-intensity exercise, a higher MyHC2 content in the vastus lateralis is accompanied by greater non-linearity in the VO2-PO relationship, as well as a steeper increase in HR in the function of an increase of PO. This relationship can be explained by greater disturbances in metabolic stability in type II muscle fibres during exercise, resulting in a decrease of muscle mechanical efficiency and greater increase of heart rate at a given power output. Therefore, MyHC composition has an impact on the oxygen cost of cycling both below and above the LT.

Metal and metalloid foliar uptake by various plant species exposed to atmospheric industrial fallout: Mechanisms involved for lead

Energy Technology Data Exchange (ETDEWEB)

Schreck, E., E-mail: eva.schreck@ensat.fr [Universite de Toulouse (France); INP, UPS (France); EcoLab (Laboratoire Ecologie Fonctionnelle et Environnement) (France); ENSAT, Avenue de l' Agrobiopole, 31326 Castanet Tolosan (France); CNRS (France); EcoLab, 31326 Castanet Tolosan (France); Foucault, Y. [Universite de Toulouse (France); INP, UPS (France); EcoLab (Laboratoire Ecologie Fonctionnelle et Environnement) (France); ENSAT, Avenue de l' Agrobiopole, 31326 Castanet Tolosan (France); CNRS (France); EcoLab, 31326 Castanet Tolosan (France); STCM, Societe de Traitements Chimiques des Metaux, 30 Avenue de Fondeyre 31200 Toulouse (France); Sarret, G. [ISTerre (UMR 5275), Universite J. Fourier and CNRS, BP 53, 38041 Grenoble cedex 9 (France); Sobanska, S. [LASIR (UMR CNRS 8516), Universite de Lille 1, Bat. C5, 59655 Villeneuve d' Ascq cedex (France); Cecillon, L. [ISTerre (UMR 5275), Universite J. Fourier and CNRS, BP 53, 38041 Grenoble cedex 9 (France); Castrec-Rouelle, M. [Universite Pierre and Marie Curie (UPMC-Paris 6), Bioemco (Biogeochimie et Ecologie des Milieux Continentaux), Site Jussieu, Tour 56, 4 Place Jussieu, 75252 Paris cedex 05 (France); Uzu, G. [Laboratoire d' Aerologie (UMR 5560), OMP, UPS 14, Avenue Edouard Belin, 31400 Toulouse (France); GET (UMR 5563), IRD, 14, Avenue Edouard Belin, 31400 Toulouse (France); Dumat, C. [Universite de Toulouse (France); INP, UPS (France); EcoLab (Laboratoire Ecologie Fonctionnelle et Environnement) (France); ENSAT, Avenue de l' Agrobiopole, 31326 Castanet Tolosan (France); CNRS (France); EcoLab, 31326 Castanet Tolosan (France)

2012-06-15

Fine and ultrafine metallic particulate matters (PMs) are emitted from metallurgic activities in peri-urban zones into the atmosphere and can be deposited in terrestrial ecosystems. The foliar transfer of metals and metalloids and their fate in plant leaves remain unclear, although this way of penetration may be a major contributor to the transfer of metals into plants. This study focused on the foliar uptake of various metals and metalloids from enriched PM (Cu, Zn, Cd, Sn, Sb, As, and especially lead (Pb)) resulting from the emissions of a battery-recycling factory. Metal and metalloid foliar uptake by various vegetable species, exhibiting different morphologies, use (food or fodder) and life-cycle (lettuce, parsley and rye-grass) were studied. The mechanisms involved in foliar metal transfer from atmospheric particulate matter fallout, using lead (Pb) as a model element was also investigated. Several complementary techniques (micro-X-ray fluorescence, scanning electron microscopy coupled with energy dispersive X-ray microanalysis and time-of-flight secondary ion mass spectrometry) were used to investigate the localization and the speciation of lead in their edible parts, i.e. leaves. The results showed lead-enriched PM on the surface of plant leaves. Biogeochemical transformations occurred on the leaf surfaces with the formation of lead secondary species (PbCO{sub 3} and organic Pb). Some compounds were internalized in their primary form (PbSO{sub 4}) underneath an organic layer. Internalization through the cuticle or penetration through stomata openings are proposed as two major mechanisms involved in foliar uptake of particulate matter. - Graphical abstract: Overall picture of performed observations and mechanisms potentially involved in lead foliar uptake. Highlights: Black-Right-Pointing-Pointer Foliar uptake of metallic particulate matter (PM) is of environmental and health concerns. Black-Right-Pointing-Pointer The leaf morphology influences the adsorption

Muscle glycogen reduction in man: relationship between surface EMG activity and oxygen uptake kinetics during heavy exercise.

Science.gov (United States)

Osborne, Mark A; Schneider, Donald A

2006-01-01

The purpose of this study was to determine whether muscle glycogen reduction prior to exercise would alter muscle fibre recruitment pattern and change either on-transient O2 uptake (VO2) kinetics or the VO2 slow component. Eight recreational cyclists (VO2peak, 55.6 +/- 1.3 ml kg (-1) min(-1)) were studied during 8 min of heavy constant-load cycling performed under control conditions (CON) and under conditions of reduced type I muscle glycogen content (GR). VO2 was measured breath-by-breath for the determination of VO2 kinetics using a double-exponential model with independent time delays. VO2 was higher in the GR trial compared to the CON trial as a result of augmented phase I and II amplitudes, with no difference between trials in the phase II time constant or the magnitude of the slow component. The mean power frequency (MPF) of electromyography activity for the vastus medialis increased over time during both trials, with a greater rate of increase observed in the GR trial compared to the CON trial. The results suggest that the recruitment of additional type II motor units contributed to the slow component in both trials. An increase in fat metabolism and augmented type II motor unit recruitment contributed to the higher VO2 in the GR trial. However, the greater rate of increase in the recruitment of type II motor units in the GR trial may not have been of sufficient magnitude to further elevate the slow component when VO2 was already high and approaching VO2peak .

Gene expression changes of single skeletal muscle fibers in response to modulation of the mitochondrial calcium uniporter (MCU

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Francesco Chemello

2015-09-01

Full Text Available The mitochondrial calcium uniporter (MCU gene codifies for the inner mitochondrial membrane (IMM channel responsible for mitochondrial Ca2+ uptake. Cytosolic Ca2+ transients are involved in sarcomere contraction through cycles of release and storage in the sarcoplasmic reticulum. In addition cytosolic Ca2+ regulates various signaling cascades that eventually lead to gene expression reprogramming. Mitochondria are strategically placed in close contact with the ER/SR, thus cytosolic Ca2+ transients elicit large increases in the [Ca2+] of the mitochondrial matrix ([Ca2+]mt. Mitochondrial Ca2+ uptake regulates energy production and cell survival. In addition, we recently showed that MCU-dependent mitochondrial Ca2+ uptake controls skeletal muscle trophism. In the same report, we dissected the effects of MCU-dependent mitochondrial Ca2+ uptake on gene expression through microarray gene expression analysis upon modulation of MCU expression by in vivo AAV infection. Analyses were performed on single skeletal muscle fibers at two time points (7 and 14 days post-AAV injection. Raw and normalized data are available on the GEO database (http://www.ncbi.nlm.nih.gov/geo/ (GSE60931.

Influence of exercise intensity on skeletal muscle blood flow, O2 extraction and O2 uptake on-kinetics

Science.gov (United States)

Jones, Andrew M; Krustrup, Peter; Wilkerson, Daryl P; Berger, Nicolas J; Calbet, José A; Bangsbo, Jens

2012-01-01

Following the start of low-intensity exercise in healthy humans, it has been established that the kinetics of skeletal muscle O2 delivery is faster than, and does not limit, the kinetics of muscle O2 uptake (). Direct data are lacking, however, on the question of whether O2 delivery might limit kinetics during high-intensity exercise. Using multiple exercise transitions to enhance confidence in parameter estimation, we therefore investigated the kinetics of, and inter-relationships between, muscle blood flow (), a– difference and following the onset of low-intensity (LI) and high-intensity (HI) exercise. Seven healthy males completed four 6 min bouts of LI and four 6 min bouts of HI single-legged knee-extension exercise. Blood was frequently drawn from the femoral artery and vein during exercise and , a– difference and were calculated and subsequently modelled using non-linear regression techniques. For LI, the fundamental component mean response time (MRTp) for kinetics was significantly shorter than kinetics (mean ± SEM, 18 ± 4 vs. 30 ± 4 s; P exercise intensities; however, the MRTp for a– difference was significantly shorter for HI compared with LI (17 ± 3 vs. 28 ± 4 s; P exercise and remained unaltered thereafter, with no differences between LI and HI. These results indicate that bulk O2 delivery does not limit kinetics following the onset of LI or HI knee-extension exercise. PMID:22711961

Glucose clearance in aged trained skeletal muscle during maximal insulin with superimposed exercise

DEFF Research Database (Denmark)

Dela, Flemming; Mikines, K J; Larsen, J J

1999-01-01

Insulin and muscle contractions are major stimuli for glucose uptake in skeletal muscle and have in young healthy people been shown to be additive. We studied the effect of superimposed exercise during a maximal insulin stimulus on glucose uptake and clearance in trained (T) (1-legged bicycle tra...

Octreotide Uptake in Parathyroid Adenoma

Directory of Open Access Journals (Sweden)

Seyhan Karaçavuş

2012-08-01

Full Text Available The patient with a history of bone pain and muscle weakness, was thought to have oncogenic osteomalacia as a result of biochemical investigations and directed to Nuclear Medicine Department for a whole-body bone scintigraphy and 111In-octreotide scintigraphy. There was no focal pathologic tracer uptake, but generalized marked increase in skeletal uptake on bone scintigraphy. Octreotide scintigraphy showed accumulation of octreotide in the region of the left lobe of the thyroid gland in the neck. Thereafter, parathyroid scintigraphy was performed with technetium-99m labeled metroxy-isobutyl-isonitryl (99mTc-MIB and MIBI scan demonstrated radiotracer uptake at the same location with octreotide scintigraphy. The patient underwent left inferior parathyroidectomy and histopathology confirmed a parathyroid adenoma. Somatostatin receptor positive parathyroid adenoma may show octreotide uptake. Octreotide scintigraphy may be promising and indicate a possibility of using somatostatin analogues for the medical treatment of somatostatin receptor positive parathyroid tumors. (MIRT 2012;21:77-79

Radioactive choline uptake in the isolated rat phrenic nerve-hemidiaphragm preparation. A biochemical and autoradiographic study

Energy Technology Data Exchange (ETDEWEB)

Veldsema-Currie, R.D.; van Marle, J.; Langemeijer, M.W.; Lind, A.; van Weeren-Kramer, J.

1984-10-01

When hemidiaphragms are stimulated via the phrenic nerve in the presence of 10 microM radioactive choline (Ch), the rate of radioactive Ch uptake in the endplate-rich area (EPA) is greater than that in the endplate-poor muscle (M). Ch uptake in the EPA is temperature-dependent, with a Q10 of 2.9 and an activation energy of 19.5 kcal/mol. It is inhibited in a Na+-depleted medium, in the absence of Ca2+, and by 10-20 microM hemicholinium-3 (HC-3) and it is not inhibited by alpha-bungarotoxin even when the muscle is completely paralyzed. In the absence of stimulation the rate of uptake in the EPA is slightly, but not significantly, greater than in M. Using autoradiography, we find an enhanced amount of isotope in the nerve terminals and their immediate vicinities compared with the muscle fibres, in both stimulated and unstimulated hemidiaphragms. There is no enhanced uptake of isotope into the nerve terminals in stimulated tissues in the presence of 26 microM HC-3. The uptake of isotope into the muscle is not altered by any of these treatments. There is a positive correlation between the initial rate of radioactive Ch uptake in the EPA and the amount of isotope in the nerve terminals (the mean corrected grain density above the nerve terminals). Without correcting for the large amount of diffusion that occurs, the ratio of the grain density above the synapses to that above the muscle fibres is 1.66 in tissue stimulated at 1 Hz, 1.04 in stimulated tissues in the presence of 26 microM HC-3, and 1.31 in unstimulated tissues.

Clinical and experimental analysis of 201thallium uptake of the heart

International Nuclear Information System (INIS)

Strauer, B.E.; Buell, U.; Buerger, S.; Klinikum Grosshadern, Muenchen

1978-01-01

Studies were carried out in order to determine the factors influencing myocardial 201 Tl uptake. A total of 158 patients was examined with regard to both 201 Tl uptake and the assessment of left ventricular and coronary function. Moreover, 42 animal experiments were performed. The results demonstrate that: 1) 201 Tl uptake in the normal and hypertrophied human heart is linearly correlated with the muscle mass of the left ventricle (LVMM); 2) 201 Tl uptake is enhanced in the inner layer and is decreased in the outer layer of the left ventricular wall. The 201 Tl uptake of the right ventricle is 40% lower in comparison to the left ventricle; 3) the basic correlation between 201 Tl uptake and LVMM is influenced by alterations of both myocardial flow and myocardial oxygen consumption; and 4) inotropic interventions (isoproterenol, calcium, norepinephrine) as well as coronary dilatation (dipyridamole) may considerably augment 201 Tl uptake in accordance with changes in myocardial oxygen consumption and/or myocardial flow. It is concluded that myocardial 201 Tl uptake is determined by multiple factors. The major determinants have been shown to include muscle mass, myocardial flow and myocardial oxygen consumption. The clinical data obtained from patient groups with normal ventricular function, with coronary artery disease, with left ventricular wall motion abnormalities and with different degree of left ventricular hypertrophy are correlated with quantitated myocardial 201 Tl uptake. (orig./MG) [de

Skeletal muscle O-GlcNAc transferase is important for muscle energy homeostasis and whole-body insulin sensitivity

DEFF Research Database (Denmark)

Shi, Hao; Munk, Alexander; Nielsen, Thomas Svava

2018-01-01

-GlcNAcylation, in skeletal muscle. METHODS: We assessed O-GlcNAcylation levels in skeletal muscle from obese, type 2 diabetic people, and we characterized muscle-specific OGT knockout (mKO) mice in metabolic cages and measured energy expenditure and substrate utilization pattern using indirect calorimetry. Whole body...... of O-GlcNAc-modified proteins in obese, type 2 diabetic people compared with well-matched obese and lean controls. Muscle-specific OGT knockout mice were lean, and whole body energy expenditure and insulin sensitivity were increased in these mice, consistent with enhanced glucose uptake and elevated...

Carbon: Nitrogen Interaction Regulates Expression of Genes Involved in N-Uptake and Assimilation in Brassica juncea L.

Science.gov (United States)

Goel, Parul; Bhuria, Monika; Kaushal, Mamta

2016-01-01

In plants, several cellular and metabolic pathways interact with each other to regulate processes that are vital for their growth and development. Carbon (C) and Nitrogen (N) are two main nutrients for plants and coordination of C and N pathways is an important factor for maintaining plant growth and development. In the present work, influence of nitrogen and sucrose (C source) on growth parameters and expression of genes involved in nitrogen transport and assimilatory pathways was studied in B. juncea seedlings. For this, B. juncea seedlings were treated with four combinations of C and N source viz., N source alone (-Suc+N), C source alone (+Suc-N), with N and C source (+Suc+N) or without N and C source (-Suc-N). Cotyledon size and shoot length were found to be increased in seedlings, when nitrogen alone was present in the medium. Distinct expression pattern of genes in both, root and shoot tissues was observed in response to exogenously supplied N and C. The presence or depletion of nitrogen alone in the medium leads to severe up- or down-regulation of key genes involved in N-uptake and transport (BjNRT1.1, BjNRT1.8) in root tissue and genes involved in nitrate reduction (BjNR1 and BjNR2) in shoot tissue. Moreover, expression of several genes, like BjAMT1.2, BjAMT2 and BjPK in root and two genes BjAMT2 and BjGS1.1 in shoot were found to be regulated only when C source was present in the medium. Majority of genes were found to respond in root and shoot tissues, when both C and N source were present in the medium, thus reflecting their importance as a signal in regulating expression of genes involved in N-uptake and assimilation. The present work provides insight into the regulation of genes of N-uptake and assimilatory pathway in B. juncea by interaction of both carbon and nitrogen. PMID:27637072

Carbon: Nitrogen Interaction Regulates Expression of Genes Involved in N-Uptake and Assimilation in Brassica juncea L.

Directory of Open Access Journals (Sweden)

Parul Goel

Full Text Available In plants, several cellular and metabolic pathways interact with each other to regulate processes that are vital for their growth and development. Carbon (C and Nitrogen (N are two main nutrients for plants and coordination of C and N pathways is an important factor for maintaining plant growth and development. In the present work, influence of nitrogen and sucrose (C source on growth parameters and expression of genes involved in nitrogen transport and assimilatory pathways was studied in B. juncea seedlings. For this, B. juncea seedlings were treated with four combinations of C and N source viz., N source alone (-Suc+N, C source alone (+Suc-N, with N and C source (+Suc+N or without N and C source (-Suc-N. Cotyledon size and shoot length were found to be increased in seedlings, when nitrogen alone was present in the medium. Distinct expression pattern of genes in both, root and shoot tissues was observed in response to exogenously supplied N and C. The presence or depletion of nitrogen alone in the medium leads to severe up- or down-regulation of key genes involved in N-uptake and transport (BjNRT1.1, BjNRT1.8 in root tissue and genes involved in nitrate reduction (BjNR1 and BjNR2 in shoot tissue. Moreover, expression of several genes, like BjAMT1.2, BjAMT2 and BjPK in root and two genes BjAMT2 and BjGS1.1 in shoot were found to be regulated only when C source was present in the medium. Majority of genes were found to respond in root and shoot tissues, when both C and N source were present in the medium, thus reflecting their importance as a signal in regulating expression of genes involved in N-uptake and assimilation. The present work provides insight into the regulation of genes of N-uptake and assimilatory pathway in B. juncea by interaction of both carbon and nitrogen.

An improved glucose transport assay system for isolated mouse skeletal muscle tissues.

Science.gov (United States)

Inagaki, Akiko; Maruo, Kanoko; Furuichi, Yasuro; Miyatake, Shouta; Tamura, Kotaro; Fujii, Nobuharu L; Manabe, Yasuko

2016-07-18

There is a growing demand for a system in the field of sarcopenia and diabetes research that could be used to evaluate the effects of functional food ingredients that enhance muscle mass/contractile force or muscle glucose uptake. In this study, we developed a new type of in vitro muscle incubation system that systemizes an apparatus for muscle incubation, using an electrode, a transducer, an incubator, and a pulse generator in a compact design. The new system enables us to analyze the muscle force stimulated by the electric pulses and glucose uptake during contraction and it may thus be a useful tool for analyzing the metabolic changes that occur during muscle contraction. The system may also contribute to the assessments of new food ingredients that act directly on skeletal muscle in the treatment of sarcopenia and diabetes.

Rolipram depresses [{sup 3}H]2-deoxyglucose uptake in mouse brain and heart in vivo

Energy Technology Data Exchange (ETDEWEB)

Ishikawa, Megumi; Hosoi, Rie; Kobayashi, Kaoru; Inoue, Osamu [Department of Medical Physics, School of Allied Health Sciences, Faculty of Medicine, Osaka University, 1-7 Yamadaoka, Suita-shi, Osaka (Japan); Nishimura, Tsunehiko [Department of Radiology, Kyoto Prefectural University of Medicine, Kyoto (Japan)

2002-09-01

The effects of systemic administration of rolipram, a selective phosphodiesterase type 4 inhibitor, on [{sup 3}H]2-deoxyglucose (DG) uptake in brain and peripheral tissues were examined. Rolipram significantly and dose-dependently decreased [{sup 3}H]DG uptake in brain, heart and skeletal muscle. In contrast, the radioactivity concentrations in the plasma of rolipram-treated mice were significantly higher than those of control mice at all times after injection of the tracer. In the kinetic study, the initial uptake of [{sup 3}H]DG in brain was decreased by rolipram, whereas no significant differences were observed in the uptake in heart and skeletal muscle. However, radioactivity concentrations in the brain, heart and skeletal muscle 30 min after the injection of [{sup 3}H]DG were significantly lowered by rolipram to about 60%, 10% and 10% of control values, respectively. The uptake of [{sup 13}N]ammonia in brain and heart of rolipram-treated mice was slightly decreased, which indicated that rolipram diminished both cerebral and cardiac blood flow. These results indicate that the phosphorylation process via hexokinase rather than the transport of [{sup 3}H]DG might be depressed by rolipram. Together with the previous observations that inhibition of protein kinase A (PKA) markedly enhanced [{sup 14}C]DG uptake in rat brain, these results indicate an important role of the cAMP/PKA systems in the regulation of glucose metabolism in the living brain as well as in peripheral tissues such as the heart and skeletal muscle. (orig.)

Experimental evidence against the mitochondrial theory of aging. A study of isolated human skeletal muscle mitochondria

DEFF Research Database (Denmark)

Rasmussen, Ulla F.; Krustrup, Peter; Kjær, Michael

2003-01-01

age effects, ATP formation, BSA effects, collagen content, low temperature spectroscopy, oxygen uptakes, quadriceps muscle, respiration, specific enzyme activities......age effects, ATP formation, BSA effects, collagen content, low temperature spectroscopy, oxygen uptakes, quadriceps muscle, respiration, specific enzyme activities...

Muscle glycogenolysis during exercise

DEFF Research Database (Denmark)

Richter, Erik; Ruderman, N B; Gavras, H

1982-01-01

glycogenolysis during exercise: contractions principally stimulate glycogenolysis early in exercise, and a direct effect of epinephrine on muscle is needed for continued glycogenolysis. In addition, epinephrine increased oxygen consumption and glucose uptake in both resting and electrically stimulated...

Semimembranosus muscle herniation: a rare case with emphasis on muscle biomechanics

Energy Technology Data Exchange (ETDEWEB)

Naffaa, Lena [American University of Beirut, Department of Diagnostic Radiology, P.O. Box 11-0236, Riad El-Solh, Beirut (Lebanon); Moukaddam, Hicham [Saint Rita Medical Center, Lima, OH (United States); Samim, Mohammad [New York University, Department of Radiology, Hospital for Joint Disease, New York, NY (United States); Lemieux, Aaron [University of California, San Diego School of Medicine, La Jolla, CA (United States); Smitaman, Edward [University of California, San Diego, Teleradiology and Education Center, San Diego, CA (United States)

2017-03-15

Muscle herniations are rare and most reported cases involve muscles of the lower leg. We use a case of muscle herniation involving the semimembranosus muscle, presenting as a painful mass in an adolescent male after an unspecified American football injury, to highlight a simple concept of muscle biomechanics as it pertains to muscle hernia(s): decreased traction upon muscle fibers can increase conspicuity of muscle herniation(s) - this allows a better understanding of the apt provocative maneuvers to employ, during dynamic ultrasound or magnetic resonance imaging, in order to maximize diagnostic yield and, thereby, limit patient morbidity related to any muscle herniation. Our patient subsequently underwent successful decompressive fasciotomy and has since returned to his normal daily activities. (orig.)

Semimembranosus muscle herniation: a rare case with emphasis on muscle biomechanics

International Nuclear Information System (INIS)

Naffaa, Lena; Moukaddam, Hicham; Samim, Mohammad; Lemieux, Aaron; Smitaman, Edward

2017-01-01

Muscle herniations are rare and most reported cases involve muscles of the lower leg. We use a case of muscle herniation involving the semimembranosus muscle, presenting as a painful mass in an adolescent male after an unspecified American football injury, to highlight a simple concept of muscle biomechanics as it pertains to muscle hernia(s): decreased traction upon muscle fibers can increase conspicuity of muscle herniation(s) - this allows a better understanding of the apt provocative maneuvers to employ, during dynamic ultrasound or magnetic resonance imaging, in order to maximize diagnostic yield and, thereby, limit patient morbidity related to any muscle herniation. Our patient subsequently underwent successful decompressive fasciotomy and has since returned to his normal daily activities. (orig.)

Cold exposure potentiates the effect of insulin on in vivo glucose uptake

International Nuclear Information System (INIS)

Vallerand, A.L.; Perusse, F.; Bukowiecki, L.J.

1987-01-01

The effects of cold exposure and insulin injection on the rates of net 2-[ 3 H]deoxyglucose uptake (K i ) in peripheral tissues were investigated in warm-acclimated rats. Cold exposure and insulin treatment independently increased K i values in skeletal muscles, heart, white adipose tissue, and brown adipose tissue. The effects of cold exposure were particularly evident in brown adipose tissue where the K i increased >100 times. When the two treatments were combined, it was found that cold exposure synergistically enhanced the maximal insulin responses for glucose uptake in brown adipose tissue, all white adipose tissue depots, and skeletal muscles investigated. The results indicate that cold exposure induces an insulin-like effect on K i that does not appear to be specifically associated with shivering thermogenesis in skeletal muscles, because that effect was observed in all insulin-sensitive tissues. The data also demonstrate that cold exposure significantly potentiates the maximal insulin responses for glucose uptake in the same tissues. This potentialization may result from (1) an enhanced responsiveness of peripheral tissues to insulin, possibly occurring at metabolic steps lying beyond the insulin receptor and (2) an increased tissue blood flow augmenting glucose and insulin availability and thereby amplifying glucose uptake

P21-activated kinase 2 (PAK2) regulates glucose uptake and insulin sensitivity in neuronal cells.

Science.gov (United States)

Varshney, Pallavi; Dey, Chinmoy Sankar

2016-07-05

P21-activated kinases (PAKs) are recently reported as important players of insulin signaling and glucose homeostasis in tissues like muscle, pancreas and liver. However, their role in neuronal insulin signaling is still unknown. Present study reports the involvement of PAK2 in neuronal insulin signaling, glucose uptake and insulin resistance. Irrespective of insulin sensitivity, insulin stimulation decreased PAK2 activity. PAK2 downregulation displayed marked enhancement of GLUT4 translocation with increase in glucose uptake whereas PAK2 over-expression showed its reduction. Treatment with Akti-1/2 and wortmannin suggested that Akt and PI3K are mediators of insulin effect on PAK2 and glucose uptake. Rac1 inhibition demonstrated decreased PAK2 activity while inhibition of PP2A resulted in increased PAK2 activity, with corresponding changes in glucose uptake. Taken together, present study demonstrates an inhibitory role of insulin signaling (via PI3K-Akt) and PP2A on PAK2 activity and establishes PAK2 as a Rac1-dependent negative regulator of neuronal glucose uptake and insulin sensitivity. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Reversible bone pain and symmetric bone scan uptake in a dialysis patient treated with cinacalcet: a case report

Directory of Open Access Journals (Sweden)

Bottino Carla

2010-06-01

Full Text Available Abstract Introduction The medical management of secondary hyperparathyroidism in patients with end-stage renal disease involves a combination of dietary restrictions, phosphate binders, active vitamin D analogs, and calcimimetics. Case presentation We report the case of a 36-year-old Hispanic dialysis patient, originally from Cuba and now residing in the USA, who developed severe bone pain and muscle twitching after starting low dose cinacalcet, despite normal pre-dialysis ionized calcium and elevated parathyroid hormone. The clinical symptoms correlated with increased symmetrical uptake on bone scan that resolved rapidly upon discontinuation of cinacalcet. Conclusion Cinacalcet may induce severe bone pain and a unique bone scan uptake pattern in hemodialysis patients.

Activation of nuclear receptor NR5A2 increases Glut4 expression and glucose metabolism in muscle cells

Energy Technology Data Exchange (ETDEWEB)

Bolado-Carrancio, A. [Department of Molecular Biology, University of Cantabria, IDIVAL, Santander (Spain); Riancho, J.A. [Department of Internal Medicine, Hospital U.M. Valdecilla-IDIVAL, University of Cantabria, RETICEF, Santander (Spain); Sainz, J. [Institute of Biomedicine and Biotechnology of Cantabria (IBBTEC), CSIC-University of Cantabria, Santander (Spain); Rodríguez-Rey, J.C., E-mail: rodriguj@unican.es [Department of Molecular Biology, University of Cantabria, IDIVAL, Santander (Spain)

2014-04-04

Highlights: • NR5A2 expression in C2C12 is associated with myotube differentiation. • DLPC induces an increase in GLUT4 levels and glucose uptake in C2C12 myotubes. • In high glucose conditions the activation of NR5A2 inhibits fatty acids oxidation. - Abstract: NR5A2 is a nuclear receptor which regulates the expression of genes involved in cholesterol metabolism, pluripotency maintenance and cell differentiation. It has been recently shown that DLPC, a NR5A2 ligand, prevents liver steatosis and improves insulin sensitivity in mouse models of insulin resistance, an effect that has been associated with changes in glucose and fatty acids metabolism in liver. Because skeletal muscle is a major tissue in clearing glucose from blood, we studied the effect of the activation of NR5A2 on muscle metabolism by using cultures of C2C12, a mouse-derived cell line widely used as a model of skeletal muscle. Treatment of C2C12 with DLPC resulted in increased levels of expression of GLUT4 and also of several genes related to glycolysis and glycogen metabolism. These changes were accompanied by an increased glucose uptake. In addition, the activation of NR5A2 produced a reduction in the oxidation of fatty acids, an effect which disappeared in low-glucose conditions. Our results suggest that NR5A2, mostly by enhancing glucose uptake, switches muscle cells into a state of glucose preference. The increased use of glucose by muscle might constitute another mechanism by which NR5A2 improves blood glucose levels and restores insulin sensitivity.

Activation of nuclear receptor NR5A2 increases Glut4 expression and glucose metabolism in muscle cells

International Nuclear Information System (INIS)

Bolado-Carrancio, A.; Riancho, J.A.; Sainz, J.; Rodríguez-Rey, J.C.

2014-01-01

Highlights: • NR5A2 expression in C2C12 is associated with myotube differentiation. • DLPC induces an increase in GLUT4 levels and glucose uptake in C2C12 myotubes. • In high glucose conditions the activation of NR5A2 inhibits fatty acids oxidation. - Abstract: NR5A2 is a nuclear receptor which regulates the expression of genes involved in cholesterol metabolism, pluripotency maintenance and cell differentiation. It has been recently shown that DLPC, a NR5A2 ligand, prevents liver steatosis and improves insulin sensitivity in mouse models of insulin resistance, an effect that has been associated with changes in glucose and fatty acids metabolism in liver. Because skeletal muscle is a major tissue in clearing glucose from blood, we studied the effect of the activation of NR5A2 on muscle metabolism by using cultures of C2C12, a mouse-derived cell line widely used as a model of skeletal muscle. Treatment of C2C12 with DLPC resulted in increased levels of expression of GLUT4 and also of several genes related to glycolysis and glycogen metabolism. These changes were accompanied by an increased glucose uptake. In addition, the activation of NR5A2 produced a reduction in the oxidation of fatty acids, an effect which disappeared in low-glucose conditions. Our results suggest that NR5A2, mostly by enhancing glucose uptake, switches muscle cells into a state of glucose preference. The increased use of glucose by muscle might constitute another mechanism by which NR5A2 improves blood glucose levels and restores insulin sensitivity

Thyroid Scan and Uptake

Medline Plus

Full Text Available ... known as a thyroid uptake. It is a measurement of thyroid function, but does not involve imaging. ... eating can affect the accuracy of the uptake measurement. Jewelry and other metallic accessories should be left ...

Thyroid Scan and Uptake

Medline Plus

Full Text Available ... Uptake? A thyroid scan is a type of nuclear medicine imaging. The radioactive iodine uptake test (RAIU) ... of thyroid function, but does not involve imaging. Nuclear medicine is a branch of medical imaging that ...

Characterization of an AtCCX5 gene from Arabidopsis thaliana that involves in high-affinity K+ uptake and Na+ transport in yeast

International Nuclear Information System (INIS)

Zhang, Xinxin; Zhang, Min; Takano, Tetsuo; Liu, Shenkui

2011-01-01

Highlights: → The AtCCX5 protein coding a putative cation calcium exchanger was characterized. → AtCCX5 expressed in yeast was localized in the plasma membrane and nuclear periphery. → AtCCX5 protein did not show the same transport properties as the CAXs. → AtCCX5 protein involves in mediating high-affinity K + uptake in yeast. → AtCCX5 protein also involves in Na + transport in yeast. -- Abstract: The gene for a putative cation calcium exchanger (CCX) from Arabidopsis thaliana, AtCCX5, was cloned and its function was analyzed in yeast. Green fluorescent protein-tagged AtCCX5 expressed in yeast was localized in the plasma membrane and nuclear periphery. The yeast transformants expressing AtCCX5 were created and their growth in the presence of various cations (K + , Na + , Ca 2+ , Mg 2+ , Fe 2+ , Cu 2+ , Co 2+ , Cd 2+ , Mn 2+ , Ba 2+ , Ni 2+ , Zn 2+ , and Li + ) were analyzed. AtCCX5 expression was found to affect the response to K + and Na + in yeast. The AtCCX5 transformant also showed a little better growth to Zn 2+ . The yeast mutant 9.3 expressing AtCCX5 restored growth of the mutant on medium with low K + (0.5 mM), and also suppressed its Na + sensitivity. Ion uptake experiments showed that AtCCX5 mediated relatively high-affinity K + uptake and was also involved in Na + transport in yeast. Taken together, these findings suggest that the AtCCX5 is a novel transport protein involves in mediating high-affinity K + uptake and Na + transport in yeast.

Endocytic pathways involved in PLGA nanoparticle uptake by grapevine cells and role of cell wall and membrane in size selection.

Science.gov (United States)

Palocci, Cleofe; Valletta, Alessio; Chronopoulou, Laura; Donati, Livia; Bramosanti, Marco; Brasili, Elisa; Baldan, Barbara; Pasqua, Gabriella

2017-12-01

PLGA NPs' cell uptake involves different endocytic pathways. Clathrin-independent endocytosis is the main internalization route. The cell wall plays a more prominent role than the plasma membrane in NPs' size selection. In the last years, many studies on absorption and cell uptake of nanoparticles by plants have been conducted, but the understanding of the internalization mechanisms is still largely unknown. In this study, polydispersed and monodispersed poly(lactic-co-glycolic) acid nanoparticles (PLGA NPs) were synthesized, and a strategy combining the use of transmission electron microscopy (TEM), confocal analysis, fluorescently labeled PLGA NPs, a probe for endocytic vesicles (FM4-64), and endocytosis inhibitors (i.e., wortmannin, ikarugamycin, and salicylic acid) was employed to shed light on PLGA NP cell uptake in grapevine cultured cells and to assess the role of the cell wall and plasma membrane in size selection of PLGA NPs. The ability of PLGA NPs to cross the cell wall and membrane was confirmed by TEM and fluorescence microscopy. A strong adhesion of PLGA NPs to the outer side of the cell wall was observed, presumably due to electrostatic interactions. Confocal microscopy and treatment with endocytosis inhibitors suggested the involvement of both clathrin-dependent and clathrin-independent endocytosis in cell uptake of PLGA NPs and the latter appeared to be the main internalization pathway. Experiments on grapevine protoplasts revealed that the cell wall plays a more prominent role than the plasma membrane in size selection of PLGA NPs. While the cell wall prevents the uptake of PLGA NPs with diameters over 50 nm, the plasma membrane can be crossed by PLGA NPs with a diameter of 500-600 nm.

Sarcoplasmic reticulum function in slow- and fast-twitch skeletal muscles from mdx mice.

Science.gov (United States)

Divet, Alexandra; Huchet-Cadiou, Corinne

2002-08-01

The aim of the present study was to establish whether alterations in sarcoplasmic reticulum function are involved in the abnormal Ca(2+) homeostasis of skeletal muscle in mice with muscular dystrophy ( mdx). The properties of the sarcoplasmic reticulum and contractile proteins of fast- and slow-twitch muscles were therefore investigated in chemically skinned fibres isolated from the extensor digitorum longus (EDL) and soleus muscles of normal (C57BL/10) and mdx mice at 4 and 11 weeks of development. Sarcoplasmic reticulum Ca(2+) uptake, estimated by the Ca(2+) release following exposure to caffeine, was significantly slower in mdx mice, while the maximal Ca(2+) quantity did not differ in either type of skeletal muscle at either stage of development. In 4-week-old mice spontaneous sarcoplasmic reticulum Ca(2+) leakage was observed in EDL and soleus fibres and this was more pronounced in mdx mice. In addition, the maximal Ca(2+)-activated tension was smaller in mdx than in normal fibres, while the Ca(2+) sensitivity of the contractile apparatus was not significantly different. These results indicate that mdx hindlimb muscles are affected differently by the disease process and suggest that a reduced ability of the Ca(2+)-ATPase to load Ca(2+) and a leaky sarcoplasmic reticulum membrane may be involved in the altered intracellular Ca(2+) homeostasis.

Rac1 signalling towards GLUT4/glucose uptake in skeletal muscle

DEFF Research Database (Denmark)

Chiu, Tim T; Jensen, Thomas Elbenhardt; Sylow, Lykke

2011-01-01

Small Rho family GTPases are important regulators of cellular traffic. Emerging evidence now implicates Rac1 and Rac-dependent actin reorganisation in insulin-induced recruitment of glucose transporter-4 (GLUT4) to the cell surface of muscle cells and mature skeletal muscle. This review summarises...... the current thinking on the regulation of Rac1 by insulin, the role of Rac-dependent cortical actin remodelling in GLUT4 traffic, and the impact of Rac1 towards insulin resistance in skeletal muscle....

Insulin signaling in skeletal muscle of HIV‐infected patients in response to endurance and strength training

DEFF Research Database (Denmark)

Broholm, Christa; Mathur, Neha; Hvid, Thine

2013-01-01

. Euglycemic-hyperinsulinemic clamps with muscle biopsies were performed before and after the training interventions. Fifteen age- and body mass index (BMI)-matched HIV-negative men served as a sedentary baseline group. Phosphorylation and total protein expression of insulin signaling molecules as well...... hexokinase II (HKII) protein. HIV-infected patients with lipodystrophy have decreased insulin-stimulated glucose uptake in skeletal muscle and defects in insulin-stimulated phosphorylation of Akt(thr308). Endurance and strength training increase insulin-stimulated glucose uptake in these patients......Human immunodeficiency virus (HIV)-infected patients with lipodystrophy have decreased insulin-stimulated glucose uptake. Both endurance and resistance training improve insulin-stimulated glucose uptake in skeletal muscle of HIV-infected patients, but the mechanisms are unknown. This study aims...

Rabbit hindlimb glucose uptake assessed with positron-emitting fluorodeoxyglucose

International Nuclear Information System (INIS)

Mossberg, K.A.; Rowe, R.W.; Tewson, T.J.; Taegtmeyer, H.

1989-01-01

The feasibility of estimating skeletal muscle glucose uptake in vivo was examined by using the glucose analogue 2-[ 18 F]deoxy-2-fluoro-D-glucose (2-[ 18 F]FDG) in the rabbit hindlimb. A pair of collimated coincidence gamma photon detectors was used to monitor the accumulation of tracer in the tissue after 2-[ 18 F]FDG injection. Time-activity curves were generated on a second-by-second basis under control conditions, during increased contractile activity, or hyperinsulinemia. The arterial input of 2-[ 18 F]FDG, plasma glucose, lactate, free fatty acids, and insulin were determined. A graphical (Patlak plot) procedure was used to determine the fractional rate of tracer phosphorylation and therefore trapping in the muscle. From the graphical analysis, the estimated rate of glucose phosphorylation (R) in the unperturbed state was calculated to be 0.037 mumol.min-1.ml-1 of tissue. During perturbation by electrical stimulation, an increase in the rate of tracer phosphorylation (K) was observed. No change in the rate of tracer phosphorylation was observed during hyperinsulinemia. The results support the use of 2-[ 18 F]FDG and the graphical procedure for the noninvasive assessment of glucose uptake by skeletal muscle in vivo. The method described is sensitive to changes in the rate of tracer uptake with respect to time and physiological interventions

[Antisynthetase syndrome without muscle involvement].

Science.gov (United States)

Júdez Navarro, Enrique; Martínez Carretero, Myriam; Martínez Jiménez, Gonzalo Fidel

2007-11-01

Antisynthetase syndrome is a well defined syndrome characterized by the presence of interstitial lung disease in association with arthritis, miositis, mechanic's hands and Ruynaud's phenomenon in the presence of antisynthetase antibodies, especially Ac anti-Jo1. We described the case of a 68-year-old man with this syndrome in the absence of inflammatory muscle disease. Copyright © 2007 Elsevier España S.L Barcelona. Published by Elsevier Espana. All rights reserved.

Involvement of two uptake mechanisms of gold and iron oxide nanoparticles in a co-exposure scenario using mouse macrophages

Directory of Open Access Journals (Sweden)

Dimitri Vanhecke

2017-11-01

Full Text Available Little is known about the simultaneous uptake of different engineered nanoparticle types, as it can be expected in our daily life. In order to test such co-exposure effects, murine macrophages (J774A.1 cell line were incubated with gold (AuNPs and iron oxide nanoparticles (FeOxNPs either alone or combined. Environmental scanning electron microscopy revealed that single NPs of both types bound within minutes on the cell surface but with a distinctive difference between FeOxNPs and AuNPs. Uptake analysis studies based on laser scanning microscopy, transmission electron microscopy, and inductively coupled plasma optical emission spectrometry revealed intracellular appearance of both NP types in all exposure scenarios and a time-dependent increase. This increase was higher for both AuNPs and FeOxNPs during co-exposure. Cells treated with endocytotic inhibitors recovered after co-exposure, which additionally hinted that two uptake mechanisms are involved. Cross-talk between uptake pathways is relevant for toxicological studies: Co-exposure acts as an uptake accelerant. If the goal is to maximize the cellular uptake, e.g., for the delivery of pharmaceutical agents, this can be beneficial. However, co-exposure should also be taken into account in the case of risk assessment of occupational settings. The demonstration of co-exposure-invoked pathway interactions reveals that synergetic nanoparticle effects, either positive or negative, must be considered for nanotechnology and nanomedicine in particular to develop to its full potential.

The proton-coupled amino acid transporter hPAT1 is the main transporter involved in vigabatrin uptake in intestinal Caco-2 cells

DEFF Research Database (Denmark)

Nøhr, Martha Kampp; Hansen, Steen Honore'; Brodin, Birger

2012-01-01

transporter hPAT1. The aim of the project was to identify if transporters are involved in cellular uptake of vigabatrin in Caco-2 cells. Methods: The uptake rate of vigabatrin was measured in Caco-2 cells at pH 6.0 or 7.4 for 15 min after application of 0.1 – 25.0 mM vigabatrin. The inhibitory effect...... of selected amino acids and -derivatives on the apical vigabatrin uptake in Caco-2 cells was investigated. Vigabatrin samples were analyzed using liquid chromatography (LC) coupled to a mass selective detector (MSD). Results: The uptake rate of vigabatrin in Caco-2 cells was pH-dependent. The uptake...... of vigabatrin was saturable at pH 6.0 with a Michaelis constant, Km of 12.7 ± 3.7 mM and a maximal flux, Jmax of 3.7 ± 0.5 nmol•min-1•cm-2. The presences of hPAT1 ligands significantly inhibited the uptake of vigabatrin in Caco-2 cells at pH 6.0, whereas hPAT1 non-ligands did not. Discussion: The saturability...

Does gallium uptake in the pulmonary hila predict involvement by non-Hodgkin's lymphoma?

International Nuclear Information System (INIS)

Champion, P.E.; Groshar, D.; Hooper, H.R.; Palmer, M.; Catz, Z.; Belch, A.; McEwan, A.

1992-01-01

67 Ga imaging of non-Hodgkin's lymphoma is useful for evaluating the presence of viable tumour in a residual mass after treatment. However, we have frequently seen gallium uptake in the pulmonary hila without other evidence of lymphoma. To study the significance of this finding, 79 patients with intermediate grade non-Hodgkin's lymphoma were reviewed. Thirty-seven (47%) had abnormal hilar gallium uptake. Twenty-three of these could be fully evaluated, and only five (22%) had hilar lymphoma. A pattern of bilateral, symmetric hilar uptake was seen in 19 patients, but only one had evidence of lymphoma. In 15 cases, this pattern was seen only on single photon emission computed tomography (SPECT). The aetiology of this uptake remains unknown. It is not treatment related, as 12 patients had hilar gallium uptake prior to chemotherapy. Unless confirmed by other methods, hilar gallium uptake should not be attributed to lymphoma, and should not influence patient management. (Author)

Bone marrow involvement in diffuse large B-cell lymphoma: correlation between FDG-PET uptake and type of cellular infiltrate

International Nuclear Information System (INIS)

Paone, Gaetano; Itti, Emmanuel; Lin, Chieh; Meignan, Michel; Haioun, Corinne; Dupuis, Jehan; Gaulard, Philippe

2009-01-01

To assess, in patients with diffuse large B-cell lymphoma (DLBCL), whether the low sensitivity of 18 F-fluorodeoxyglucose positron emission tomography (FDG-PET) for bone marrow assessment may be explained by histological characteristics of the cellular infiltrate. From a prospective cohort of 110 patients with newly diagnosed aggressive lymphoma, 21 patients with DLBCL had bone marrow involvement. Pretherapeutic FDG-PET images were interpreted visually and semiquantitatively, then correlated with the type of cellular infiltrate and known prognostic factors. Of these 21 patients, 7 (33%) had lymphoid infiltrates with a prominent component of large transformed lymphoid cells (concordant bone marrow involvement, CBMI) and 14 (67%) had lymphoid infiltrates composed of small cells (discordant bone marrow involvement, DBMI). Only 10 patients (48%) had abnormal bone marrow FDG uptake, 6 of the 7 with CBMI and 4 of the 14 with DBMI. Therefore, FDG-PET positivity in the bone marrow was significantly associated with CBMI, while FDG-PET negativity was associated with DBMI (Fisher's exact test, p=0.024). There were no significant differences in gender, age and overall survival between patients with CBMI and DBMI, while the international prognostic index was significantly higher in patients with CBMI. Our study suggests that in patients with DLBCL with bone marrow involvement bone marrow FDG uptake depends on two types of infiltrate, comprising small (DBMI) or large (CBMI) cells. This may explain the apparent low sensitivity of FDG-PET previously reported for detecting bone marrow involvement. (orig.)

Enhanced fatty acid oxidation and FATP4 protein expression after endurance exercise training in human skeletal muscle

DEFF Research Database (Denmark)

Jeppesen, Jacob; Jordy, Andreas B; Sjøberg, Kim A

2012-01-01

; however, it is not known whether this involves up-regulation of FATP1 and FATP4 protein. Therefore, the aim of this project was to investigate FATP1 and FATP4 protein expression in the vastus lateralis muscle from healthy human individuals and to what extent FATP1 and FATP4 protein expression were......FATP1 and FATP4 appear to be important for the cellular uptake and handling of long chain fatty acids (LCFA). These findings were obtained from loss- or gain of function models. However, reports on FATP1 and FATP4 in human skeletal muscle are limited. Aerobic training enhances lipid oxidation...

Application of dynamic metabolomics to examine in vivo skeletal muscle glucose metabolism in the chronically high-fat fed mouse

Energy Technology Data Exchange (ETDEWEB)

Kowalski, Greg M., E-mail: greg.kowalski@deakin.edu.au [Centre for Physical Activity and Nutrition Research, School of Exercise and Nutrition Sciences, Deakin University, Burwood, Victoria 3125 (Australia); De Souza, David P. [Metabolomics Australia, Bio21 Institute of Molecular Science and Biotechnology, University of Melbourne, Parkville, Victoria 3010 (Australia); Burch, Micah L. [Brigham and Women' s Hospital, Department of Medicine, Boston, MA (United States); Hamley, Steven [Centre for Physical Activity and Nutrition Research, School of Exercise and Nutrition Sciences, Deakin University, Burwood, Victoria 3125 (Australia); Kloehn, Joachim [Metabolomics Australia, Bio21 Institute of Molecular Science and Biotechnology, University of Melbourne, Parkville, Victoria 3010 (Australia); Selathurai, Ahrathy [Centre for Physical Activity and Nutrition Research, School of Exercise and Nutrition Sciences, Deakin University, Burwood, Victoria 3125 (Australia); Tull, Dedreia; O' Callaghan, Sean; McConville, Malcolm J. [Metabolomics Australia, Bio21 Institute of Molecular Science and Biotechnology, University of Melbourne, Parkville, Victoria 3010 (Australia); Bruce, Clinton R. [Centre for Physical Activity and Nutrition Research, School of Exercise and Nutrition Sciences, Deakin University, Burwood, Victoria 3125 (Australia)

2015-06-19

Rationale: Defects in muscle glucose metabolism are linked to type 2 diabetes. Mechanistic studies examining these defects rely on the use of high fat-fed rodent models and typically involve the determination of muscle glucose uptake under insulin-stimulated conditions. While insightful, they do not necessarily reflect the physiology of the postprandial state. In addition, most studies do not examine aspects of glucose metabolism beyond the uptake process. Here we present an approach to study rodent muscle glucose and intermediary metabolism under the dynamic and physiologically relevant setting of the oral glucose tolerance test (OGTT). Methods and results: In vivo muscle glucose and intermediary metabolism was investigated following oral administration of [U-{sup 13}C] glucose. Quadriceps muscles were collected 15 and 60 min after glucose administration and metabolite flux profiling was determined by measuring {sup 13}C mass isotopomers in glycolytic and tricarboxylic acid (TCA) cycle intermediates via gas chromatography–mass spectrometry. While no dietary effects were noted in the glycolytic pathway, muscle from mice fed a high fat diet (HFD) exhibited a reduction in labelling in TCA intermediates. Interestingly, this appeared to be independent of alterations in flux through pyruvate dehydrogenase. In addition, our findings suggest that TCA cycle anaplerosis is negligible in muscle during an OGTT. Conclusions: Under the dynamic physiologically relevant conditions of the OGTT, skeletal muscle from HFD fed mice exhibits alterations in glucose metabolism at the level of the TCA cycle. - Highlights: • Dynamic metabolomics was used to investigate muscle glucose metabolism in vivo. • Mitochondrial TCA cycle metabolism is altered in muscle of HFD mice. • This defect was not pyruvate dehydrogenase mediated, as has been previously thought. • Mitochondrial TCA cycle anaplerosis in muscle is virtually absent during the OGTT.

Application of dynamic metabolomics to examine in vivo skeletal muscle glucose metabolism in the chronically high-fat fed mouse

International Nuclear Information System (INIS)

Kowalski, Greg M.; De Souza, David P.; Burch, Micah L.; Hamley, Steven; Kloehn, Joachim; Selathurai, Ahrathy; Tull, Dedreia; O'Callaghan, Sean; McConville, Malcolm J.; Bruce, Clinton R.

2015-01-01

Rationale: Defects in muscle glucose metabolism are linked to type 2 diabetes. Mechanistic studies examining these defects rely on the use of high fat-fed rodent models and typically involve the determination of muscle glucose uptake under insulin-stimulated conditions. While insightful, they do not necessarily reflect the physiology of the postprandial state. In addition, most studies do not examine aspects of glucose metabolism beyond the uptake process. Here we present an approach to study rodent muscle glucose and intermediary metabolism under the dynamic and physiologically relevant setting of the oral glucose tolerance test (OGTT). Methods and results: In vivo muscle glucose and intermediary metabolism was investigated following oral administration of [U- 13 C] glucose. Quadriceps muscles were collected 15 and 60 min after glucose administration and metabolite flux profiling was determined by measuring 13 C mass isotopomers in glycolytic and tricarboxylic acid (TCA) cycle intermediates via gas chromatography–mass spectrometry. While no dietary effects were noted in the glycolytic pathway, muscle from mice fed a high fat diet (HFD) exhibited a reduction in labelling in TCA intermediates. Interestingly, this appeared to be independent of alterations in flux through pyruvate dehydrogenase. In addition, our findings suggest that TCA cycle anaplerosis is negligible in muscle during an OGTT. Conclusions: Under the dynamic physiologically relevant conditions of the OGTT, skeletal muscle from HFD fed mice exhibits alterations in glucose metabolism at the level of the TCA cycle. - Highlights: • Dynamic metabolomics was used to investigate muscle glucose metabolism in vivo. • Mitochondrial TCA cycle metabolism is altered in muscle of HFD mice. • This defect was not pyruvate dehydrogenase mediated, as has been previously thought. • Mitochondrial TCA cycle anaplerosis in muscle is virtually absent during the OGTT

Lipolysis in Skeletal Muscle

DEFF Research Database (Denmark)

Serup, Annette Karen Lundbeck

chemical structure of DAG. We took advantage of the fact that insulin sensitivity is increased after exercise, and that mice knocked out (KO) of HSL accumulate DAG after exercise, and measured insulin stimulated glucose uptake after treadmill running in skeletal muscle from HSL KO mice and wildtype control...

Alpha-adrenergic receptors in rat skeletal muscle

DEFF Research Database (Denmark)

Rattigan, S; Appleby, G J; Edwards, S J

1986-01-01

Sarcolemma-enriched preparations from muscles rich in slow oxidative red fibres contained specific binding sites for the alpha 1 antagonist, prazosin (e.g. soleus Kd 0.13 nM, Bmax 29 fmol/mg protein). Binding sites for prazosin were almost absent from white muscle. Displacement of prazosin bindin...... adrenergic receptors are present on the sarcolemma of slow oxidative red fibres of rat skeletal muscle. The presence provides the mechanistic basis for apparent alpha-adrenergic effects to increase glucose and oxygen uptake in perfused rat hindquarter....

MURC, a muscle-restricted coiled-coil protein, is involved in the regulation of skeletal myogenesis.

Science.gov (United States)

Tagawa, Masashi; Ueyama, Tomomi; Ogata, Takehiro; Takehara, Naofumi; Nakajima, Norio; Isodono, Koji; Asada, Satoshi; Takahashi, Tomosaburo; Matsubara, Hiroaki; Oh, Hidemasa

2008-08-01

Skeletal myogenesis is a multistep process by which multinucleated mature muscle fibers are formed from undifferentiated, mononucleated myoblasts. However, the molecular mechanisms of skeletal myogenesis have not been fully elucidated. Here, we identified muscle-restricted coiled-coil (MURC) protein as a positive regulator of myogenesis. In skeletal muscle, MURC was localized to the cytoplasm with accumulation in the Z-disc of the sarcomere. In C2C12 myoblasts, MURC expression occurred coincidentally with myogenin expression and preceded sarcomeric myosin expression during differentiation into myotubes. RNA interference (RNAi)-mediated knockdown of MURC impaired differentiation in C2C12 myoblasts, which was accompanied by impaired myogenin expression and ERK activation. Overexpression of MURC in C2C12 myoblasts resulted in the promotion of differentiation with enhanced myogenin expression and ERK activation during differentiation. During injury-induced muscle regeneration, MURC expression increased, and a higher abundance of MURC was observed in immature myofibers compared with mature myofibers. In addition, ERK was activated in regenerating tissue, and ERK activation was detected in MURC-expressing immature myofibers. These findings suggest that MURC is involved in the skeletal myogenesis that results from modulation of myogenin expression and ERK activation. MURC may play pivotal roles in the molecular mechanisms of skeletal myogenic differentiation.

Skeletal muscle bioenergetics during all-out exercise: mechanistic insight into the oxygen uptake slow component and neuromuscular fatigue.

Science.gov (United States)

Broxterman, Ryan M; Layec, Gwenael; Hureau, Thomas J; Amann, Markus; Richardson, Russell S

2017-05-01

and skeletal muscle bioenergetics underlying all-out exercise performance are unclear. This study revealed an increase in oxidative ATP synthesis rate gain and the ATP cost of contraction during all-out exercise. Furthermore, peripheral fatigue was related to the perturbation in pH and deprotonated phosphate ion. These findings support the concept that the oxygen uptake slow component arises from within active skeletal muscle and that skeletal muscle force generating capacity is linked to the intramuscular metabolic milieu.

Cell uptake mechanisms of PAMAM G4-FITC dendrimer in human myometrial cells

International Nuclear Information System (INIS)

Oddone, Natalia; Zambrana, Ana I.; Tassano, Marcos; Porcal, Williams; Cabral, Pablo; Benech, Juan C.

2013-01-01

The high incidence and severity of diseases which involve smooth muscle dysfunction dictates the need of continued search for novel therapeutic strategies to treat these conditions. Dendrimers are branched macromolecules with multiple end-groups that can be functionalized for applications which include drug delivery. There is no data regarding the cellular uptake mechanisms used by dendrimers in smooth muscle human myometrial cells (HMC). Polyamidoamine G4 dendrimers were conjugated with fluorescein isothiocyanate (FITC) and the resulting conjugate (G4-FITC) was characterized using high-performance liquid chromatography, nuclear magnetic resonance, and atomic force microscopy. G4-FITC showed to have no significant effect on the primary culture HMC viability up to 48 h. HMC incubated with G4-FITC were analyzed by laser confocal microscopy. Peri-nuclear fluorescence distribution was observed at 5 h of incubation or more (24, 36, and 48 h). At 24 h, G4-FITC partially co-localized with lysotracker. Uptake of G4-FITC by HMC was slightly inhibited by filipin (8.0 ± 3.9 %) and significantly inhibited by chlorpromazine (63.5 ± 3.7 %). In non-electroporated HMC, G4-FITC was never observed inside the cell nucleus. Interestingly, we detected G4-FITC inside the nuclear domain of some electroporated cells. Thus, electroporation changed intracellular G4-FITC localization. Isolated nuclei of HMC incubated with G4-FITC showed fluorescence signal inside the nuclear domain. The results suggest that in HMC, G4-FITC is taken up by clathrin-mediated endocytosis with endosomal and lysosomal localization at 24 h. The combination of electroporation and dendrimers could be an interesting technology to electrotransfer drugs into smooth muscle cells cytosol and nuclei

Cell uptake mechanisms of PAMAM G4-FITC dendrimer in human myometrial cells

Energy Technology Data Exchange (ETDEWEB)

Oddone, Natalia; Zambrana, Ana I.; Tassano, Marcos [Instituto de Investigaciones Biologicas Clemente Estable, Laboratorio de Senalizacion Celular y Nanobiologia (Uruguay); Porcal, Williams [Universidad de la Republica, Grupo de Quimica Medicinal, Instituto de Quimica Biologica, Facultad de Ciencias-Facultad de Quimica (Uruguay); Cabral, Pablo [Universidad de la Republica, Laboratorio de Radiofarmacia, Centro de Investigaciones Nucleares, Facultad de Ciencias (Uruguay); Benech, Juan C., E-mail: benech@iibce.edu.uy [Instituto de Investigaciones Biologicas Clemente Estable, Laboratorio de Senalizacion Celular y Nanobiologia (Uruguay)

2013-07-15

The high incidence and severity of diseases which involve smooth muscle dysfunction dictates the need of continued search for novel therapeutic strategies to treat these conditions. Dendrimers are branched macromolecules with multiple end-groups that can be functionalized for applications which include drug delivery. There is no data regarding the cellular uptake mechanisms used by dendrimers in smooth muscle human myometrial cells (HMC). Polyamidoamine G4 dendrimers were conjugated with fluorescein isothiocyanate (FITC) and the resulting conjugate (G4-FITC) was characterized using high-performance liquid chromatography, nuclear magnetic resonance, and atomic force microscopy. G4-FITC showed to have no significant effect on the primary culture HMC viability up to 48 h. HMC incubated with G4-FITC were analyzed by laser confocal microscopy. Peri-nuclear fluorescence distribution was observed at 5 h of incubation or more (24, 36, and 48 h). At 24 h, G4-FITC partially co-localized with lysotracker. Uptake of G4-FITC by HMC was slightly inhibited by filipin (8.0 {+-} 3.9 %) and significantly inhibited by chlorpromazine (63.5 {+-} 3.7 %). In non-electroporated HMC, G4-FITC was never observed inside the cell nucleus. Interestingly, we detected G4-FITC inside the nuclear domain of some electroporated cells. Thus, electroporation changed intracellular G4-FITC localization. Isolated nuclei of HMC incubated with G4-FITC showed fluorescence signal inside the nuclear domain. The results suggest that in HMC, G4-FITC is taken up by clathrin-mediated endocytosis with endosomal and lysosomal localization at 24 h. The combination of electroporation and dendrimers could be an interesting technology to electrotransfer drugs into smooth muscle cells cytosol and nuclei.

Neuronal nitric oxide synthase mediates insulin- and oxidative stress-induced glucose uptake in skeletal muscle myotubes.

Science.gov (United States)

Kellogg, Dean L; McCammon, Karen M; Hinchee-Rodriguez, Kathryn S; Adamo, Martin L; Roman, Linda J

2017-09-01

Previously published studies strongly suggested that insulin- and exercise-induced skeletal muscle glucose uptake require nitric oxide (NO) production. However, the signal transduction mechanisms by which insulin and contraction regulated NO production and subsequent glucose transport are not known. In the present study, we utilized the myotube cell lines treated with insulin or hydrogen peroxide, the latter to mimic contraction-induced oxidative stress, to characterize these mechanisms. We found that insulin stimulation of neuronal nitric oxide synthase (nNOS) phosphorylation, NO production, and GLUT4 translocation were all significantly reduced by inhibition of either nNOS or Akt2. Hydrogen peroxide (H 2 O 2 ) induced phosphorylation of nNOS at the same residue as did insulin, and also stimulated NO production and GLUT4 translocation. nNOS inhibition prevented H 2 O 2 -induced GLUT4 translocation. AMP activated protein kinase (AMPK) inhibition prevented H 2 O 2 activation and phosphorylation of nNOS, leading to reduced NO production and significantly attenuated GLUT4 translocation. We conclude that nNOS phosphorylation and subsequently increased NO production are required for both insulin- and H 2 O 2 -stimulated glucose transport. Although the two stimuli result in phosphorylation of the same residue on nNOS, they do so through distinct protein kinases. Thus, insulin and H 2 O 2 -activated signaling pathways converge on nNOS, which is a common mediator of glucose uptake in both pathways. However, the fact that different kinases are utilized provides a basis for the use of exercise to activate glucose transport in the face of insulin resistance. Copyright © 2017. Published by Elsevier Inc.

Nitric oxide is required for the insulin sensitizing effects of contraction in mouse skeletal muscle.

Science.gov (United States)

Zhang, Xinmei; Hiam, Danielle; Hong, Yet-Hoi; Zulli, Anthony; Hayes, Alan; Rattigan, Stephen; McConell, Glenn K

2017-12-15

People with insulin resistance or type 2 diabetes can substantially increase their skeletal muscle glucose uptake during exercise and insulin sensitivity after exercise. Skeletal muscle nitric oxide (NO) is important for glucose uptake during exercise, although how prior exercise increases insulin sensitivity is unclear. In the present study, we examined whether NO is necessary for normal increases in skeletal muscle insulin sensitivity after contraction ex vivo in mouse muscle. The present study uncovers, for the first time, a novel role for NO in the insulin sensitizing effects of ex vivo contraction, which is independent of blood flow. The factors regulating the increase in skeletal muscle insulin sensitivity after exercise are unclear. We examined whether nitric oxide (NO) is required for the increase in insulin sensitivity after ex vivo contractions. Isolated C57BL/6J mouse EDL muscles were contracted for 10 min or remained at rest (basal) with or without the NO synthase (NOS) inhibition (N G -monomethyl-l-arginine; l-NMMA; 100 μm). Then, 3.5 h post contraction/basal, muscles were exposed to saline or insulin (120 μU ml -1 ) with or without l-NMMA during the last 30 min. l-NMMA had no effect on basal skeletal muscle glucose uptake. The increase in muscle glucose uptake with insulin (57%) was significantly (P contraction (140% increase). NOS inhibition during the contractions had no effect on this insulin-sensitizing effect of contraction, whereas NOS inhibition during insulin prevented the increase in skeletal muscle insulin sensitivity post-contraction. Soluble guanylate cyclase inhibition, protein kinase G (PKG) inhibition or cyclic nucleotide phosphodiesterase inhibition each had no effect on the insulin-sensitizing effect of prior contraction. In conclusion, NO is required for increases in insulin sensitivity several hours after contraction of mouse skeletal muscle via a cGMP/PKG independent pathway. © 2017 The Authors. The Journal of Physiology

Differential Muscle Involvement in Mice and Humans Affected by McArdle Disease

DEFF Research Database (Denmark)

Krag, Thomas O; Pinós, Tomàs; Nielsen, Tue L

2016-01-01

McArdle disease (muscle glycogenosis type V) is caused by myophosphorylase deficiency, which leads to impaired glycogen breakdown. We investigated how myophosphorylase deficiency affects muscle physiology, morphology, and glucose metabolism in 20-week-old McArdle mice and compared the findings...... to those in McArdle disease patients. Muscle contractions in the McArdle mice were affected by structural degeneration due to glycogen accumulation, and glycolytic muscles fatigued prematurely, as occurs in the muscles of McArdle disease patients. Homozygous McArdle mice showed muscle fiber disarray...... no substitution for the missing muscle isoform. In the mice, the tibialis anterior (TA) muscles were invariably more damaged than the quadriceps muscles. This may relate to a 7-fold higher level of myophosphorylase in TA compared to quadriceps in wild-type mice and suggests higher glucose turnover in the TA. Thus...

AMPK in skeletal muscle function and metabolism

DEFF Research Database (Denmark)

Kjøbsted, Rasmus; Hingst, Janne Rasmuss; Fentz, Joachim

2018-01-01

Skeletal muscle possesses a remarkable ability to adapt to various physiologic conditions. AMPK is a sensor of intracellular energy status that maintains energy stores by fine-tuning anabolic and catabolic pathways. AMPK's role as an energy sensor is particularly critical in tissues displaying...... highly changeable energy turnover. Due to the drastic changes in energy demand that occur between the resting and exercising state, skeletal muscle is one such tissue. Here, we review the complex regulation of AMPK in skeletal muscle and its consequences on metabolism (e.g., substrate uptake, oxidation......, and storage as well as mitochondrial function of skeletal muscle fibers). We focus on the role of AMPK in skeletal muscle during exercise and in exercise recovery. We also address adaptations to exercise training, including skeletal muscle plasticity, highlighting novel concepts and future perspectives...

Inflammatory cytokines and hypoxia contribute to 18F-FDG uptake by cells involved in pannus formation in rheumatoid arthritis.

Science.gov (United States)

Matsui, Tamiko; Nakata, Norihito; Nagai, Shigenori; Nakatani, Akira; Takahashi, Miwako; Momose, Toshimitsu; Ohtomo, Kuni; Koyasu, Shigeo

2009-06-01

Assessment of the activity of rheumatoid arthritis (RA) is important for the prediction of future articular destruction. (18)F-FDG PET is known to represent the metabolic activity of inflammatory disease, which correlates with the pannus volume measured by MRI or ultrasonography. To evaluate the correlation between (18)F-FDG accumulation and RA pathology, we assessed (18)F-FDG accumulation in vivo using collagen-induced arthritis (CIA) animal models and (3)H-FDG uptake in vitro using various cells involved in arthritis. (18)F-FDG PET images of rats with CIA were acquired on days 10, 14, and 17 after arthritis induction. The specimens were subsequently subjected to macroautoradiography, and the (18)F-FDG accumulation was compared with the histologic findings. (3)H-FDG uptake in vitro in inflammatory cells (neutrophils, macrophages, T cells, and fibroblasts) was measured to evaluate the contributions of these cells to (18)F-FDG accumulation. In addition, the influence on (3)H-FDG uptake of inflammatory factors, such as cytokines (tumor necrosis factor alpha [TNFalpha], interleukin 1 [IL-1], and IL-6), and hypoxia was examined. (18)F-FDG PET depicted swollen joints, and (18)F-FDG accumulation increased with the progression of arthritis. Histologically, a higher level of (18)F-FDG accumulation correlated with the pannus rather than the infiltration of inflammatory cells around the joints. In the in vitro (3)H-FDG uptake assay, fibroblasts showed the highest (3)H-FDG uptake, followed by neutrophils. Although only a small amount of (3)H-FDG was incorporated by resting macrophages, a dramatic increase in (3)H-FDG uptake in both fibroblasts and macrophages was observed when these cells were exposed to inflammatory cytokines, such as TNFalpha and IL-1, and hypoxia. Although neutrophils showed relatively high (3)H-FDG uptake without activation, no increase in (3)H-FDG uptake was observed in response to inflammatory cytokines. (3)H-FDG uptake by T cells was much lower than

Coronary and muscle blood flow during physical exercise in humans; heterogenic alliance.

Science.gov (United States)

Zoladz, Jerzy A; Majerczak, Joanna; Duda, Krzysztof; Chlopicki, Stefan

2015-08-01

In this review, we present the relation between power generation capabilities and pulmonary oxygen uptake during incremental cycling exercise in humans and the effect of exercise intensity on the oxygen cost of work. We also discuss the importance of oxygen delivery to the working muscles as a factor determining maximal oxygen uptake in humans. Subsequently, we outline the importance of coronary blood flow, myocardial oxygen uptake and myocardial metabolic stability for exercise tolerance. Finally, we describe mechanisms of endothelium-dependent regulation of coronary and skeletal muscle blood flow, dysregulation of which may impair exercise capacity and increase the cardiovascular risk of exercise. Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. All rights reserved.

Endurance training facilitates myoglobin desaturation during muscle contraction in rat skeletal muscle.

Science.gov (United States)

Takakura, Hisashi; Furuichi, Yasuro; Yamada, Tatsuya; Jue, Thomas; Ojino, Minoru; Hashimoto, Takeshi; Iwase, Satoshi; Hojo, Tatsuya; Izawa, Tetsuya; Masuda, Kazumi

2015-03-24

At onset of muscle contraction, myoglobin (Mb) immediately releases its bound O2 to the mitochondria. Accordingly, intracellular O2 tension (PmbO2) markedly declines in order to increase muscle O2 uptake (mVO2). However, whether the change in PmbO2 during muscle contraction modulates mVO2 and whether the O2 release rate from Mb increases in endurance-trained muscles remain unclear. The purpose of this study was, therefore, to determine the effect of endurance training on O2 saturation of Mb (SmbO2) and PmbO2 kinetics during muscle contraction. Male Wistar rats were subjected to a 4-week swimming training (Tr group; 6 days per week, 30 min × 4 sets per day) with a weight load of 2% body mass. After the training period, deoxygenated Mb kinetics during muscle contraction were measured using near-infrared spectroscopy under hemoglobin-free medium perfusion. In the Tr group, the VmO2peak significantly increased by 32%. Although the PmbO2 during muscle contraction did not affect the increased mVO2 in endurance-trained muscle, the O2 release rate from Mb increased because of the increased Mb concentration and faster decremental rate in SmbO2 at the maximal twitch tension. These results suggest that the Mb dynamics during muscle contraction are contributing factors to faster VO2 kinetics in endurance-trained muscle.

Muscle MRI findings in facioscapulohumeral muscular dystrophy

Energy Technology Data Exchange (ETDEWEB)

Gerevini, Simonetta; Caliendo, Giandomenico; Falini, Andrea [IRCCS San Raffaele Scientific Institute, Neuroradiology Unit, Head and Neck Department, Milan (Italy); Scarlato, Marina; Previtali, Stefano Carlo [IRCCS San Raffaele Scientific Institute, Department of Neurology, INSPE and Division of Neuroscience, Milan (Italy); Maggi, Lorenzo; Pasanisi, Barbara; Morandi, Lucia [Fondazione IRCCS Istituto Neurologico ' ' Carlo Besta' ' , Neuromuscular Diseases and Neuroimmunology Unit, Milan (Italy); Cava, Mariangela [IRCCS San Raffaele Scientific Institute, Department of Radiology and Center for Experimental Imaging, Milan (Italy)

2016-03-15

Facioscapulohumeral muscular dystrophy (FSHD) is characterized by extremely variable degrees of facial, scapular and lower limb muscle involvement. Clinical and genetic determination can be difficult, as molecular analysis is not always definitive, and other similar muscle disorders may have overlapping clinical manifestations. Whole-body muscle MRI examination for fat infiltration, atrophy and oedema was performed to identify specific patterns of muscle involvement in FSHD patients (30 subjects), and compared to a group of control patients (23) affected by other myopathies (NFSHD). In FSHD patients, we detected a specific pattern of muscle fatty replacement and atrophy, particularly in upper girdle muscles. The most frequently affected muscles, including paucisymptomatic and severely affected FSHD patients, were trapezius, teres major and serratus anterior. Moreover, asymmetric muscle involvement was significantly higher in FSHD as compared to NFSHD patients. In conclusion, muscle MRI is very sensitive for identifying a specific pattern of involvement in FSHD patients and in detecting selective muscle involvement of non-clinically testable muscles. Muscle MRI constitutes a reliable tool for differentiating FSHD from other muscular dystrophies to direct diagnostic molecular analysis, as well as to investigate FSHD natural history and follow-up of the disease. (orig.)

Design of compounds having enhanced tumour uptake, using serum albumin as a carrier. Pt. 2

International Nuclear Information System (INIS)

Schilling, U.; Friedrich, E.A.; Sinn, H.; Schrenk, H.H.; Clorius, J.H.; Maier-Borst, W.

1992-01-01

In the present in vivo study the uptake kinetics of radioiodinated albumin were determined in normal organs, and tumours of rats using sequential scintigraphy. Results indicate that cellular uptake of the marker takes place. Fluorescence was not observed in muscle tissue. This appears to suggest that the albumin uptake is greater in tumours than in normal tissue, and that it is metabolized in the tumour cells. (Author)

Effects of Coffee Components on Muscle Glycogen Recovery: A Systematic Review.

Science.gov (United States)

Loureiro, Laís Monteiro Rodrigues; Reis, Caio Eduardo Gonçalves; da Costa, Teresa Helena Macedo

2018-01-18

Coffee is one of the most consumed beverages in the world and it can improve insulin sensitivity, stimulating glucose uptake in skeletal muscle when adequate carbohydrate intake is observed. The aim of this review is to analyze the effects of coffee and coffee components on muscle glycogen metabolism. A literature search was conducted according to PRISMA and seven studies were included. They explored the effects of coffee components on various substances and signaling proteins. In one of the studies with humans, caffeine was shown to increase glucose levels, Ca 2+ /calmodulin-dependent protein kinase (CaMK) phosphorylation, glycogen resynthesis rates and glycogen accumulation after exercise. After intravenous injection of caffeine in rats, caffeine increased adenosine monophosphate-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) phosphorylation, and glucose transport. In in vitro studies caffeine raised AMPK and ACC phosphorylation, increasing glucose transport activity and reducing energy status in rat muscle cells. Cafestol and caffeic acid increased insulin secretion in rat beta-cells, and glucose uptake into human muscle cells. Caffeic acid also increased AMPK and ACC phosphorylation, reducing the energy status and increasing glucose uptake in rat muscle cells. Chlorogenic acid did not show any positive or negative effect. The findings from the current review must be taken with caution due to the limited number of studies on the subject. In conclusion, various coffee components had a neutral or positive role in the metabolism of glucose and muscle glycogen, whilst no detrimental effect was described. Coffee beverages should be tested as an option for athlete's glycogen recovery.

Human skeletal muscle fatty acid and glycerol metabolism during rest, exercise and recovery

DEFF Research Database (Denmark)

Van Hall, Gerrit; Sacchetti, M; Rådegran, G

2002-01-01

glycerol uptake was observed, which was substantially higher during exercise. Total body skeletal muscle FA and glycerol uptake/release was estimated to account for 18-25 % of whole body R(d) or R(a). In conclusion: (1) skeletal muscle FA and glycerol metabolism, using the leg arterial-venous difference......This study was conducted to investigate skeletal muscle fatty acid (FA) and glycerol kinetics and to determine the contribution of skeletal muscle to whole body FA and glycerol turnover during rest, 2 h of one-leg knee-extensor exercise at 65 % of maximal leg power output, and 3 h of recovery....... To this aim, the leg femoral arterial-venous difference technique was used in combination with a continuous infusion of [U-(13)C]palmitate and [(2)H(5)]glycerol in five post-absorptive healthy volunteers (22 +/- 3 years). The influence of contamination from non-skeletal muscle tissues, skin and subcutaneous...

Mechanisms for greater insulin-stimulated glucose uptake in normal and insulin-resistant skeletal muscle after acute exercise

Science.gov (United States)

2015-01-01

Enhanced skeletal muscle and whole body insulin sensitivity can persist for up to 24–48 h after one exercise session. This review focuses on potential mechanisms for greater postexercise and insulin-stimulated glucose uptake (ISGU) by muscle in individuals with normal or reduced insulin sensitivity. A model is proposed for the processes underlying this improvement; i.e., triggers initiate events that activate subsequent memory elements, which store information that is relayed to mediators, which translate memory into action by controlling an end effector that directly executes increased insulin-stimulated glucose transport. Several candidates are potential triggers or memory elements, but none have been conclusively verified. Regarding potential mediators in both normal and insulin-resistant individuals, elevated postexercise ISGU with a physiological insulin dose coincides with greater Akt substrate of 160 kDa (AS160) phosphorylation without improved proximal insulin signaling at steps from insulin receptor binding to Akt activity. Causality remains to be established between greater AS160 phosphorylation and improved ISGU. The end effector for normal individuals is increased GLUT4 translocation, but this remains untested for insulin-resistant individuals postexercise. Following exercise, insulin-resistant individuals can attain ISGU values similar to nonexercising healthy controls, but after a comparable exercise protocol performed by both groups, ISGU for the insulin-resistant group has been consistently reported to be below postexercise values for the healthy group. Further research is required to fully understand the mechanisms underlying the improved postexercise ISGU in individuals with normal or subnormal insulin sensitivity and to explain the disparity between these groups after similar exercise. PMID:26487009

Studies on muscle metabolism in peripheral vascular disease using 201Tl

International Nuclear Information System (INIS)

Safi, N.; Chanachai, R.; Blanquet, P.; Texier, L.; Passeron, A.; Guillet, G.

1982-01-01

Thallium 201 has been used mostly in cardiology, for the detection of ischemic ''areas'' and infarcted zones in cardiac muscle. This isotope has been chosen, because of its great metabolic similarity to Potassium. But less interest has been shown in the transit and localization of Thallium in the limbs. We have been working on a method based upon the study of muscle metabolism using 201 Tl which could possibly detect the condition before the onset of clinical symptoms. As a preliminary investigation, we have studied the distribution of this isotope, in rats after effort, or in resting state. We have observed an important increase in the muscle uptake of 201 Tl during the period of effort compared to the uptake in a resting state. The ratio of this increased uptake is about two to three times more important. In vitro studies of fibroblast cell cultures reveal a competition between potassium and thallium, the fixation of thallium being diminished in the presence of an excess of potassium and increased when the concentration of potassium is low, in the culture medium

Uptake and release of 3H-benzo(a)pyrene by arterial cells in vivo and in vitro

International Nuclear Information System (INIS)

Pessah-Rasmussen, H.; Stavenow, L.

1989-01-01

Cigarette smoking is an established risk factor for the development of clinical manifestations of atherosclerosis. The atherogenicity of the different components of cigarette smoke is still subject to debate. One possible mechanism is that tarderived hydrocarbons might exert toxic and/or mutagenic effects in the arterial wall including a monoclonal proliferation of smooth muscle cells. There is evidence that polycyclic aromatic hydrocarbons (PAH) from cigarette smoke can get access to the blood and that they are transported in plasma lipoproteins. Treatment of chickens with benzo(a)pyrene (BaP) induced or potentiated the development of atherosclerotic lesions. Others have studied the uptake of BaP by fibroblasts in culture. The fate of PAH in the arterial wall and in smooth muscle cells has not been clarified yet. The purpose of the present report was to study the uptake and release of BaP in smooth muscle cells in culture and the uptake of BaP in the arterial wall in vivo. (author)

Disorders of muscle lipid metabolism: diagnostic and therapeutic challenges.

Science.gov (United States)

Laforêt, Pascal; Vianey-Saban, Christine

2010-11-01

Disorders of muscle lipid metabolism may involve intramyocellular triglyceride degradation, carnitine uptake, long-chain fatty acids mitochondrial transport, or fatty acid β-oxidation. Three main diseases leading to permanent muscle weakness are associated with severe increased muscle lipid content (lipid storage myopathies): primary carnitine deficiency, neutral lipid storage disease and multiple acyl-CoA dehydrogenase deficiency. A moderate lipidosis may be observed in fatty acid oxidation disorders revealed by rhabdomyolysis episodes such as carnitine palmitoyl transferase II, very-long-chain acyl-CoA dehydrogenase, mitochondrial trifunctional protein deficiencies, and in recently described phosphatidic acid phosphatase deficiency. Respiratory chain disorders and congenital myasthenic syndromes may also be misdiagnosed as fatty acid oxidation disorders due to the presence of secondary muscle lipidosis. The main biochemical tests giving clues for the diagnosis of these various disorders are measurements of blood carnitine and acylcarnitines, urinary organic acid profile, and search for intracytoplasmic lipid on peripheral blood smear (Jordan's anomaly). Genetic analysis orientated by the results of biochemical investigation allows establishing a firm diagnosis. Primary carnitine deficiency and multiple acyl-CoA dehydrogenase deficiency may be treated after supplementation with carnitine, riboflavine and coenzyme Q10. New therapeutic approaches for fatty acid oxidation disorders are currently developed, based on pharmacological treatment with bezafibrate, and specific diets enriched in medium-chain triglycerides or triheptanoin. Copyright © 2010 Elsevier B.V. All rights reserved.

Pathogenesis of Insulin Resistance in Skeletal Muscle

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Muhammad A. Abdul-Ghani

2010-01-01

Full Text Available Insulin resistance in skeletal muscle is manifested by decreased insulin-stimulated glucose uptake and results from impaired insulin signaling and multiple post-receptor intracellular defects including impaired glucose transport, glucose phosphorylation, and reduced glucose oxidation and glycogen synthesis. Insulin resistance is a core defect in type 2 diabetes, it is also associated with obesity and the metabolic syndrome. Dysregulation of fatty acid metabolism plays a pivotal role in the pathogenesis of insulin resistance in skeletal muscle. Recent studies have reported a mitochondrial defect in oxidative phosphorylation in skeletal muscle in variety of insulin resistant states. In this review, we summarize the cellular and molecular defects that contribute to the development of insulin resistance in skeletal muscle.

MRI for the demonstration of subclinical muscle involvement in muscular dystrophy

International Nuclear Information System (INIS)

Sookhoo, S.; MacKinnon, I.; Bushby, K.; Chinnery, P.F.; Birchall, D.

2007-01-01

Aim: To compare magnetic resonance imaging (MRI) with clinical examination for the detection of muscle abnormality in patients with muscular dystrophy. Methods: Muscle power in 20 patients with a variety of forms of muscular dystrophy was examined clinically using the Medical Research Council (MRC) grading scale, and patients were subsequently imaged with MRI. MRI and clinical examination for the detection of muscle normality and abnormality were compared using a McNemar chi-squared test to examine differences between the two methods. Results: MRI demonstrated radiological evidence of muscle abnormality more often than clinical examination; 50% of movements assessed as normal on clinical examination were associated with muscle abnormalities on MRI, including a significant proportion where there was severe radiological abnormality, indicating that focally advanced disease may be undetectable clinically. Conclusion: The combination of clinical examination and MRI could improve the accuracy of phenotypic characterization of patients with muscular dystrophy, and this in turn could allow a more focussed molecular analysis through muscle biopsy or genetic investigation. This may also be very helpful in the assessment of the degree of muscle compromise not only in the early phases of the disease but especially during follow-up and can be used in therapeutic trials

Contrasting effects of exercise and NOS inhibition on tissue-specific fatty acid and glucose uptake in mice.

Science.gov (United States)

Rottman, Jeffrey N; Bracy, Deanna; Malabanan, Carlo; Yue, Zou; Clanton, Jeff; Wasserman, David H

2002-07-01

Isotopic techniques were used to test the hypothesis that exercise and nitric oxide synthase (NOS) inhibition have distinct effects on tissue-specific fatty acid and glucose uptakes in a conscious, chronically catheterized mouse model. Uptakes were measured using the radioactive tracers (125)I-labeled beta-methyl-p-iodophenylpentadecanoic acid (BMIPP) and deoxy-[2-(3)H]glucose (DG) during treadmill exercise with and without inhibition of NOS. [(125)I]BMIPP uptake at rest differed substantially among tissues with the highest levels in heart. With exercise, [(125)I]BMIPP uptake increased in both heart and skeletal muscles. In sedentary mice, NOS inhibition induced by nitro-L-arginine methyl ester (L-NAME) feeding increased heart and soleus [(125)I]BMIPP uptake. In contrast, exercise, but not L-NAME feeding, resulted in increased heart and skeletal muscle [2-(3)H]DG uptake. Significant interactions were not observed in the effects of combined exercise and L-NAME feeding on [(125)I]BMIPP and [2-(3)H]DG uptakes. In the conscious mouse, exercise and NOS inhibition produce distinct patterns of tissue-specific fatty acid and glucose uptake; NOS is not required for important components of exercise-associated metabolic signaling, or other mechanisms compensate for the absence of this regulatory mechanism.

The ATP required for potentiation of skeletal muscle contraction is released via pannexin hemichannels.

Science.gov (United States)

Riquelme, Manuel A; Cea, Luis A; Vega, José L; Boric, Mauricio P; Monyer, Hannah; Bennett, Michael V L; Frank, Marina; Willecke, Klaus; Sáez, Juan C

2013-12-01

During repetitive stimulation of skeletal muscle, extracellular ATP levels raise, activating purinergic receptors, increasing Ca2+ influx, and enhancing contractile force, a response called potentiation. We found that ATP appears to be released through pannexin1 hemichannels (Panx1 HCs). Immunocytochemical analyses and function were consistent with pannexin1 localization to T-tubules intercalated with dihydropyridine and ryanodine receptors in slow (soleus) and fast (extensor digitorum longus, EDL) muscles. Isolated myofibers took up ethidium (Etd+) and released small molecules (as ATP) during electrical stimulation. Consistent with two glucose uptake pathways, induced uptake of 2-NBDG, a fluorescent glucose derivative, was decreased by inhibition of HCs or glucose transporter (GLUT4), and blocked by dual blockade. Adult skeletal muscles apparently do not express connexins, making it unlikely that connexin hemichannels contribute to the uptake and release of small molecules. ATP release, Etd+ uptake, and potentiation induced by repetitive electrical stimulation were blocked by HC blockers and did not occur in muscles of pannexin1 knockout mice. MRS2179, a P2Y1R blocker, prevented potentiation in EDL, but not soleus muscles, suggesting that in fast muscles ATP activates P2Y1 but not P2X receptors. Phosphorylation on Ser and Thr residues of pannexin1 was increased during potentiation, possibly mediating HC opening. Opening of Panx1 HCs during repetitive activation allows efflux of ATP, influx of glucose and possibly Ca2+ too, which are required for potentiation of contraction. This article is part of the Special Issue Section entitled 'Current Pharmacology of Gap Junction Channels and Hemichannels'. Copyright © 2013 Elsevier Ltd. All rights reserved.

Mechanisms limiting glycogen storage in muscle during prolonged insulin stimulation

International Nuclear Information System (INIS)

Richter, E.A.; Hansen, S.A.; Hansen, B.F.

1988-01-01

The extent to which muscle glycogen concentrations can be increased during exposure to maximal insulin concentrations and abundant glucose was investigated in the isolated perfused rat hindquarter preparation. Perfusion for 7 h in the presence of 20,000 μU/ml insulin and 11-13 mM glucose increased muscle glycogen concentrations to maximal values 2, 3, and 3.5 times above normal fed levels in fast-twitch white, slow-twitch red, and fast-twitch red fibers, respectively. Glucose uptake decreased from 34.9 μmol·g -1 ·h -1 at 0 h to 7.5 after 7 h of perfusion. During the perfusion muscle glycogen synthase activity decreased and free intracellular glucose and glucose 6-phosphate increased indicating that glucose disposal was impaired. However, glucose transport as measured by the uptake of 3-O-[ 14 C]methyl-D-glucose was also markedly decreased after 5 and 7 h of perfusion compared with initial values. Total muscle water concentration decreased during glycogen loading of the muscles. Mechanisms limiting glycogen storage under maximal insulin stimulation include impaired insulin-stimulated membrane transport of glucose as well as impaired intracellular glucose disposal

Extent and distribution of skeletal muscle necrosis after graded periods of complete ischemia

International Nuclear Information System (INIS)

Labbe, R.; Lindsay, T.; Walker, P.M.

1987-01-01

The management of an acutely ischemic extremity requires knowledge of the response of skeletal muscle (the largest component of the lower limb) to prolonged periods of complete normothermic ischemia. We have used the canine gracilis muscle model to evaluate the extent and distribution of ischemic necrosis after 3 and 5 hours of ischemia and 48 hours of reperfusion. Each muscle was cut into six slices, and the extent and distribution of postischemic necrosis identified by means of nitroblue tetrazolium staining and 99mTc pyrophosphate uptake. After 3, 4, and 5 hours of ischemia the extent of necrosis was 2.0% +/- 0.9%, 30.3% +/- 6.0%, and 90.1% +/- 3.5% (mean +/- SEM), respectively. A statistically significant correlation exists between the extent of necrosis and the uptake of 99mTc pyrophosphate uptake per gram of tissue (y = 1574.9x - 8.4, r = 0.84, p less than 0.001). Most necrosis was centrally located and found in the thickest portion of the muscle. We conclude that there is a graded response in the extent of skeletal muscle necrosis related to the length of ischemic stress rather than an ''all-or-none'' phenomenon. This central distribution of necrosis makes the usual external evaluation of ischemic damage clinically unreliable. In addition, since there was no enveloping fascia in this model, a compartment release alone may not prevent the development of skeletal muscle necrosis. This knowledge of the response of skeletal muscle to ischemia may lead to an improved clinical approach to an extremity suffering a prolonged ischemic insult

Pregnancy-induced insulin resistance in liver and skeletal muscles of the conscious rabbit

International Nuclear Information System (INIS)

Hauguel, S.; Gilbert, M.; Girard, J.

1987-01-01

Insulin sensitivity of maternal nonuterine tissues (liver and skeletal muscles) has been investigated in the conscious rabbit during late gestation (24 and 30 days). The specific effect of insulin on glucose production and utilization was evaluated with the hyperinsulinemic euglycemic clamp technique using two types of labelled microspheres ( 57 Co and 113 Sn). The net balance of glucose across the hindlimb muscles was studied by means of the Fick principle in basal and insulin stimulated conditions (clamp study). The results show that an insulin-resistant state developed between days 24 and 30 of gestation in the rabbit and involves both glucose producing (liver) and utilizing (muscles) tissues. On day 30 of gestation, muscle glucose uptake was not significantly stimulated at a plasma insulin concentration of 700 μU/ml determined by radioimmunoassay, whereas it was stimulated by 30-40% in nonpregnant and 24 day pregnant rabbits. At similar plasma insulin concentration, endogenous glucose production was suppressed by 85% in both nonpregnant and 24 day pregnant rabbits, whereas it was decreased by only 30% in 30 day pregnant rabbits. The present data suggest that hindlimb muscles of late pregnant rabbits are able to reduce their insulin-induced glucose utilization. This could contribute to meet the glucose requirements of pregnant uterus in late gestation

Potentiation of cGMP signaling increases oxygen delivery and oxidative metabolism in contracting skeletal muscle of older but not young humans

DEFF Research Database (Denmark)

Nyberg, Michael Permin; Piil, Peter Bergmann; Egelund, Jon

2015-01-01

regulation remain unresolved. Cyclic guanosine monophosphate (cGMP) is one of the main second messengers that mediate smooth muscle vasodilation and alterations in cGMP signaling could, therefore, be one mechanism by which skeletal muscle perfusion is impaired with advancing age. The current study aimed...... to evaluate the effect of inhibiting the main enzyme involved in cGMP degradation, phosphodiesterase 5 (PDE5), on blood flow and O2 delivery in contracting skeletal muscle of young and older humans. A group of young (23 ± 1 years) and a group of older (72 ± 2 years) male human subjects performed submaximal...... in the older subjects correlated with the increase in leg O2 uptake (r (2) = 0.843). These findings suggest an insufficient O2 delivery to the contracting skeletal muscle of aged individuals and that reduced cGMP availability is a novel mechanism underlying impaired skeletal muscle perfusion with advancing age....

An aqueous extract of Curcuma longa (turmeric) rhizomes stimulates insulin release and mimics insulin action on tissues involved in glucose homeostasis in vitro.

Science.gov (United States)

Mohankumar, Sureshkumar; McFarlane, James R

2011-03-01

Curcuma longa (turmeric) has been used widely as a spice, particularly in Asian countries. It is also used in the Ayurvedic system of medicine as an antiinflammatory and antimicrobial agent and for numerous other curative properties. The aim of this study was to investigate the effects of an aqueous extract of Curcuma longa (AEC) on tissues involved in glucose homeostasis. The extract was prepared by soaking 100 g of ground turmeric in 1 L of water, which was filtered and stored at -20°C prior to use. Pancreas and muscle tissues of adult mice were cultured in DMEM with 5 or 12 mmol/L glucose and varying doses of extract. The AEC stimulated insulin secretion from mouse pancreatic tissues under both basal and hyperglycaemic conditions, although the maximum effect was only 68% of that of tolbutamide. The AEC induced stepwise stimulation of glucose uptake from abdominal muscle tissues in the presence and absence of insulin, and the combination of AEC and insulin significantly potentiated the glucose uptake into abdominal muscle tissue. However, this effect was attenuated by wortmannin, suggesting that AEC possibly acts via the insulin-mediated glucose uptake pathway. In summary, water soluble compounds of turmeric exhibit insulin releasing and mimicking actions within in vitro tissue culture conditions. Copyright © 2010 John Wiley & Sons, Ltd.

Lactate Accumulation in Muscle and Blood during Submaximal Exercise

Science.gov (United States)

1981-09-21

exercise, fast and slow twitch fibers Short title: Lactate in muscle and blood P.A. Tesch, W.L. Daniels and D.S. Sharp Exercise Physiology Division, U.S...KIRBY, R.L. & BELCASTRO, A.N. 1978. Relationship between slow - twitch muscle fibres and lactic acid removal. Can J Appl Sports Sci 3:160-162. BRODAL, P...oxygen uptake (Karlsson 1971, Knuttgen & Saltin 1972). It is generally agreed that the main muscle fiber type to be recruited below this level is the slow

Muscle oxygen kinetics at onset of intense dynamic exercise in humans

DEFF Research Database (Denmark)

Bangsbo, J; Krustrup, P; González-Alonso, J

2000-01-01

The present study examined the onset and the rate of rise of muscle oxidation during intense exercise in humans and whether oxygen availability limits muscle oxygen uptake in the initial phase of intense exercise. Six subjects performed 3 min of intense one-legged knee-extensor exercise [65.3 +/-...

Rac1 is a novel regulator of contraction-stimulated glucose uptake in skeletal muscle

DEFF Research Database (Denmark)

Sylow, Lykke; Jensen, Thomas Elbenhardt; Kleinert, Maximilian

2013-01-01

In skeletal muscle, the actin cytoskeleton-regulating GTPase, Rac1, is necessary for insulin-dependent GLUT4 translocation. Muscle contraction increases glucose transport and represents an alternative signaling pathway to insulin. Whether Rac1 is activated by muscle contraction and regulates...

Evidence for the involvement of the CXCL12 system in the adaptation of skeletal muscles to physical exercise.

Science.gov (United States)

Puchert, Malte; Adams, Volker; Linke, Axel; Engele, Jürgen

2016-09-01

The chemokine CXCL12 and its primary receptor, CXCR4, not only promote developmental myogenesis, but also muscle regeneration. CXCL12 chemoattracts CXCR4-positive satellite cells/blood-borne progenitors to the injured muscle, promotes myoblast fusion, partially with existing myofibers, and induces angiogenesis in regenerating muscles. Interestingly, the mechanisms underlying muscle regeneration are in part identical to those involved in muscular adaptation to intensive physical exercise. These similarities now prompted us to determine whether physical exercise would impact the CXCL12 system in skeletal muscle. We found that CXCL12 and CXCR4 are upregulated in the gastrocnemius muscle of rats that underwent a four-week period of constrained daily running exercise on a treadmill. Double-staining experiments confirmed that CXCL12 and CXCR4 are predominantly expressed in MyHC-positive muscle fibers. Moreover, these training-dependent increases in CXCL12 and CXCR4 expression also occurred in rats with surgical coronary artery occlusion, implying that the muscular CXCL12 system is still active in skeletal myopathy resulting from chronic heart failure. Expression of the second CXCL12 receptor, CXCR7, which presumably acts as a scavenger receptor in muscle, was not affected by training. Attempts to dissect the molecular events underlying the training-dependent effects of CXCL12 revealed that the CXCL12-CXCR4 axis activates anabolic mTOR-p70S6K signaling and prevents upregulation of the catabolic ubiquitin ligase MurF-1 in C2C12 myotubes, eventually increasing myotube diameters. Together, these findings point to a pivotal role of the CXCL12-CXCR4 axis in exercise-induced muscle maintenance and/or growth. Copyright © 2016 Elsevier Inc. All rights reserved.

Membrane proteins involved in potassium shifts during muscle activity and fatigue

DEFF Research Database (Denmark)

Kristensen, Michael; Hansen, T.; Juel, C.

2006-01-01

while trying to manipulate the opening probability or transport capacity of these proteins during electrical stimulation of isolated soleus muscles. All experiments were made with excised muscle from male Wistar rats. Kir2.1 channels were almost undetectable in the sarcolemmal membrane but present...... muscle contractions, whereas Kir2.1 and NKCC1 may have a role in K+ reuptake. channels and cotransporters; T tubule...

The RabGAP TBC1D1 plays a central role in exercise-regulated glucose metabolism in skeletal muscle

DEFF Research Database (Denmark)

Stöckli, Jacqueline; Meoli, Christopher C; Hoffman, Nolan J

2015-01-01

Insulin and exercise stimulate glucose uptake into skeletal muscle via different pathways. Both stimuli converge on the translocation of the glucose transporter GLUT4 from intracellular vesicles to the cell surface. Two Rab guanosine triphosphatases-activating proteins (GAPs) have been implicated...... weight, insulin action, and exercise. TBC1D1(-/-) mice showed normal glucose and insulin tolerance, with no difference in body weight compared with wild-type littermates. GLUT4 protein levels were reduced by ∼40% in white TBC1D1(-/-) muscle, and TBC1D1(-/-) mice showed impaired exercise endurance...... together with impaired exercise-mediated 2-deoxyglucose uptake into white but not red muscles. These findings indicate that the RabGAP TBC1D1 plays a key role in regulating GLUT4 protein levels and in exercise-mediated glucose uptake in nonoxidative muscle fibers....

Normal insulin-stimulated endothelial function and impaired insulin-stimulated muscle glucose uptake in young adults with low birth weight

DEFF Research Database (Denmark)

Hermann, T S; Rask-Madsen, C; Ihlemann, N

2003-01-01

of acetylcholine and sodium nitroprusside in the forearm of fourteen 21-yr-old men with low birth weight and 16 controls of normal birth weight. Glucose uptake was measured during intraarterial insulin infusion. Dose-response studies were repeated during insulin infusion. The maximal blood flow during......Low birth weight has been linked to insulin resistance and cardiovascular disease. We hypothesized that insulin sensitivity of both muscle and vascular tissues were impaired in young men with low birth weight. Blood flow was measured by venous occlusion plethysmography during dose-response studies...... acetylcholine infusion was 14.1 +/- 2.7 and 14.4 +/- 2.1 [ml x (100 ml forearm)(-1) x min(-1)] in low and normal birth weight subjects, respectively. Insulin coinfusion increased acetylcholine-stimulated flow in both groups: 18.0 +/- 3.1 vs. 17.9 +/- 3.1 [ml x (100 ml forearm)(-1) x min(-1)], NS. Insulin...

Estrogen receptor beta is involved in skeletal muscle hypertrophy induced by the phytoecdysteroid ecdysterone.

Science.gov (United States)

Parr, Maria Kristina; Zhao, Piwen; Haupt, Oliver; Ngueu, Sandrine Tchoukouegno; Hengevoss, Jonas; Fritzemeier, Karl Heinrich; Piechotta, Marion; Schlörer, Nils; Muhn, Peter; Zheng, Wen-Ya; Xie, Ming-Yong; Diel, Patrick

2014-09-01

The phytoectysteroid ecdysterone (Ecdy) was reported to stimulate protein synthesis and enhance physical performance. The aim of this study was to investigate underlying molecular mechanisms particularly the role of ER beta (ERβ). In male rats, Ecdy treatment increased muscle fiber size, serum IGF-1 increased, and corticosteron and 17β-estradiol (E2) decreased. In differentiated C2C12 myoblastoma cells, treatment with Ecdy, dihydrotestosterone, IGF-1 but also E2 results in hypertrophy. Hypertrophy induced by E2 and Ecdy could be antagonized with an antiestrogen but not by an antiandrogen. In HEK293 cells transfected with ER alpha (ERα) or ERβ, Ecdy treatment transactivated a reporter gene. To elucidate the role of ERβ in Ecdy-mediated muscle hypertrophy, C2C12 myotubes were treated with ERα (ALPHA) and ERβ (BETA) selective ligands. Ecdy and BETA treatment but not ALPHA induced hypertrophy. The effect of Ecdy, E2, and BETA could be antagonized by an ERβ-selective antagonist (ANTIBETA). In summary, our results indicate that ERβ is involved in the mediation of the anabolic activity of the Ecdy. These findings provide new therapeutic perspectives for the treatment of muscle injuries, sarcopenia, and cachectic disease, but also imply that such a substance could be abused for doping purposes. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Metabolic Disturbance in PCOS: Clinical and Molecular Effects on Skeletal Muscle Tissue

Directory of Open Access Journals (Sweden)

Wagner Silva Dantas

2013-01-01

Full Text Available Polycystic ovary syndrome is a complex hormonal disorder affecting the reproductive and metabolic systems with signs and symptoms related to anovulation, infertility, menstrual irregularity and hirsutism. Skeletal muscle plays a vital role in the peripheral glucose uptake. Since PCOS is associated with defects in the activation and pancreatic dysfunction of β-cell insulin, it is important to understand the molecular mechanisms of insulin resistance in PCOS. Studies of muscle tissue in patients with PCOS reveal defects in insulin signaling. Muscle biopsies performed during euglycemic hyperinsulinemic clamp showed a significant reduction in glucose uptake, and insulin-mediated IRS-2 increased significantly in skeletal muscle. It is recognized that the etiology of insulin resistance in PCOS is likely to be as complicated as in type 2 diabetes and it has an important role in metabolic and reproductive phenotypes of this syndrome. Thus, further evidence regarding the effect of nonpharmacological approaches (e.g., physical exercise in skeletal muscle of women with PCOS is required for a better therapeutic approach in the management of various metabolic and reproductive problems caused by this syndrome.

Metabolic disturbance in PCOS: clinical and molecular effects on skeletal muscle tissue.

Science.gov (United States)

Dantas, Wagner Silva; Gualano, Bruno; Rocha, Michele Patrocínio; Barcellos, Cristiano Roberto Grimaldi; dos Reis Vieira Yance, Viviane; Marcondes, José Antonio Miguel

2013-01-01

Polycystic ovary syndrome is a complex hormonal disorder affecting the reproductive and metabolic systems with signs and symptoms related to anovulation, infertility, menstrual irregularity and hirsutism. Skeletal muscle plays a vital role in the peripheral glucose uptake. Since PCOS is associated with defects in the activation and pancreatic dysfunction of β-cell insulin, it is important to understand the molecular mechanisms of insulin resistance in PCOS. Studies of muscle tissue in patients with PCOS reveal defects in insulin signaling. Muscle biopsies performed during euglycemic hyperinsulinemic clamp showed a significant reduction in glucose uptake, and insulin-mediated IRS-2 increased significantly in skeletal muscle. It is recognized that the etiology of insulin resistance in PCOS is likely to be as complicated as in type 2 diabetes and it has an important role in metabolic and reproductive phenotypes of this syndrome. Thus, further evidence regarding the effect of nonpharmacological approaches (e.g., physical exercise) in skeletal muscle of women with PCOS is required for a better therapeutic approach in the management of various metabolic and reproductive problems caused by this syndrome.

[Molecular mechanism for ET-1-induced insulin resistance in skeletal muscle cells].

Science.gov (United States)

Horinouchi, Takahiro; Mazaki, Yuichi; Terada, Koji; Miwa, Soichi

2018-01-01

Insulin resistance is a condition where the sensitivity to insulin of the tissues expressing insulin receptor (InsR) is decreased due to a functional disturbance of InsR-mediated intracellular signaling. Insulin promotes the entry of glucose into the tissues and skeletal muscle is the most important tissue responsible for the insulin's action of decreasing blood glucose levels. Endothelin-1 (ET-1), a potent vasoconstrictor and pro-inflammatory peptide, induces insulin resistance through a direct action on skeletal muscle. However, the signaling pathways of ET-1-induced insulin resistance in skeletal muscle remain unclear. Here we show molecular mechanism underlying the inhibitory effect of ET-1 on insulin-stimulated Akt phosphorylation and glucose uptake in myotubes of rat L6 skeletal muscle cell line. mRNA expression levels of differentiation marker genes, MyoD and myogenin, were increased during L6 myoblasts differentiation into myotubes. Some of myotubes possessed the ability to spontaneously contract. In myotubes, insulin promoted Akt phosphorylation at Thr 308 and Ser 473 , and [ 3 H]-labelled 2-deoxy-D-glucose ([ 3 H]2-DG) uptake. The insulin-facilitated Akt phosphorylation and [ 3 H]2-DG uptake were inhibited by ET-1. The inhibitory effect of ET-1 was counteracted by blockade of ET type A receptor (ET A R), inhibition of G q/11 protein, and siRNA knockdown of G protein-coupled receptor kinase 2 (GRK2). The exogenously overexpressed GRK2 directly bound to endogenous Akt and their association was facilitated by ET-1. In summary, activation of ET A R with ET-1 inhibits insulin-induced Akt phosphorylation and [ 3 H]2-DG uptake in a G q/11 protein- and GRK2-dependent manner in skeletal muscle. These findings indicate that ET A R and GRK2 are potential targets for insulin resistance.

Comparison of histomorphometry and 85Sr uptake in induced heterotopic bone in rats

DEFF Research Database (Denmark)

Solheim, E; Pinholt, E M; Bang, G

1992-01-01

Heterotopic bone formation in the abdominal muscle of 45 male 8-week-old Wistar rats induced by implantation of 5, 10, or 15 mg demineralized bone (DBM) powder was evaluated at 4 weeks by 85Sr uptake of the implants and area histomorphometry of the induced bone. Two indices of 85Sr uptake were...... with increasing mass of implanted DBM, whereas the osteogenic index did not change....

Gibberellin Is Involved in Inhibition of Cucumber Growth and Nitrogen Uptake at Suboptimal Root-Zone Temperatures.

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Longqiang Bai

Full Text Available Suboptimal temperature stress often causes heavy yield losses of vegetables by suppressing plant growth during winter and early spring. Gibberellin acid (GA has been reported to be involved in plant growth and acquisition of mineral nutrients. However, no studies have evaluated the role of GA in the regulation of growth and nutrient acquisition by vegetables under conditions of suboptimal temperatures in greenhouse. Here, we investigated the roles of GA in the regulation of growth and nitrate acquisition of cucumber (Cucumis sativus L. plants under conditions of short-term suboptimal root-zone temperatures (Tr. Exposure of cucumber seedlings to a Tr of 16°C led to a significant reduction in root growth, and this inhibitory effect was reversed by exogenous application of GA. Expression patterns of several genes encoding key enzymes in GA metabolism were altered by suboptimal Tr treatment, and endogenous GA concentrations in cucumber roots were significantly reduced by exposure of cucumber plants to 16°C Tr, suggesting that inhibition of root growth by suboptimal Tr may result from disruption of endogenous GA homeostasis. To further explore the mechanism underlying the GA-dependent cucumber growth under suboptimal Tr, we studied the effect of suboptimal Tr and GA on nitrate uptake, and found that exposure of cucumber seedlings to 16°C Tr led to a significant reduction in nitrate uptake rate, and exogenous application GA can alleviate the down-regulation by up regulating the expression of genes associated with nitrate uptake. Finally, we demonstrated that N accumulation in cucumber seedlings under suboptimal Tr conditions was improved by exogenous application of GA due probably to both enhanced root growth and nitrate absorption activity. These results indicate that a reduction in endogenous GA concentrations in roots due to down-regulation of GA biosynthesis at transcriptional level may be a key event to underpin the suboptimal Tr

Locomotor muscle fatigue does not alter oxygen uptake kinetics during high-intensity exercise

Directory of Open Access Journals (Sweden)

James Hopker

2016-10-01

Full Text Available The slow component (VO2sc that develops during high-intensity aerobic exercise is thought to be strongly associated with locomotor muscle fatigue. We sought to experimentally test this hypothesis by pre-fatiguing the locomotor muscles used during subsequent high-intensity cycling exercise. Over two separate visits, eight healthy male participants were asked to either perform a non-metabolically stressful 100 intermittent drop-jumps protocol (pre fatigue condition or rest for 33 minutes (control condition according to a random and counterbalanced order. Locomotor muscle fatigue was quantified with 6-second maximal sprints at a fixed pedaling cadence of 90 rev·min-1. Oxygen kinetics and other responses (heart rate, capillary blood lactate concentration and rating of perceived exertion, RPE were measured during two subsequent bouts of 6 min cycling exercise at 50% of the delta between the lactate threshold and VO2max determined during a preliminary incremental exercise test. All tests were performed on the same cycle ergometer. Despite significant locomotor muscle fatigue (P = 0.03, the VO2sc was not significantly different between the pre fatigue (464 ± 301 mL·min-1 and the control (556 ± 223 mL·min-1 condition (P = 0.50. Blood lactate response was not significantly different between conditions (P = 0.48 but RPE was significantly higher following the pre-fatiguing exercise protocol compared with the control condition (P < 0.01 suggesting higher muscle recruitment. These results demonstrate experimentally that locomotor muscle fatigue does not significantly alter the VO2 kinetic response to high intensity aerobic exercise, and challenge the hypothesis that the VO2sc is strongly associated with locomotor muscle fatigue.

99mTc-sestamibi muscle scintigraphy to assess the response to neuromuscular electrical stimulation of normal quadriceps femoris muscle

International Nuclear Information System (INIS)

Pekindil, Y.; Sarikaya, A.; Birtane, M.; Pekindil, G.; Salan, A.

2001-01-01

Neuromuscular electrical stimulation (NMES) is widely used for improving muscle strength by simultaneous contraction in the prevention of muscle atrophy. Although there exist many clinical methods for evaluating the therapeutic response of muscles, 99m Tc-sestamibi which is a skeletal muscle perfusion and metabolism agent has not previously been used for this purpose. The aim of our work was to ascertain whether 99m Tc-sestamibi muscle scintigraphy is useful in the monitoring of therapeutic response to NMES in healthy women. The study included 16 women aged between 21 and 45, with a mean age of 32.7±6.4. Both quadriceps femoris muscles (QFM) of each patient were studied. After randomization to remove the effect of the dominant side, one QFM of each patient was subjected to the NMES procedure for a period of 20 days. NMES was performed with an alternating biphasic rectangular current, from a computed electrical stimulator daily for 23 minutes. After measurement of skinfold thickness over the thigh, pre- and post-NMES girth measurements were assessed in centimeters. Sixty minutes after injections of 555 MBq 99m Tc-sestamibi, static images of the thigh were obtained for 5 minutes. The thigh-to-knee uptake ratio was calculated by semiquantitative analysis and normalized to body surface area (NUR=normalized uptake ratio). The difference between the pre and post NMES NUR values was significant (1.76±0.31 versus 2.25±0.38, p=0.0000). The percentage (%) increase in NUR values also well correlated with the % increase in thigh girth measurements (r=0.89, p=0.0000). These results indicated that 99m Tc-sestamibi muscle scintigraphy as a new tool may be useful in evaluating therapeutic response to NMES. (author)

Metabolic Circuit Involving Free Fatty Acids, microRNA 122, and Triglyceride Synthesis in Liver and Muscle Tissues.

Science.gov (United States)

Chai, Chofit; Rivkin, Mila; Berkovits, Liav; Simerzin, Alina; Zorde-Khvalevsky, Elina; Rosenberg, Nofar; Klein, Shiri; Yaish, Dayana; Durst, Ronen; Shpitzen, Shoshana; Udi, Shiran; Tam, Joseph; Heeren, Joerg; Worthmann, Anna; Schramm, Christoph; Kluwe, Johannes; Ravid, Revital; Hornstein, Eran; Giladi, Hilla; Galun, Eithan

2017-11-01

Effective treatments are needed for hepatic steatosis characterized by accumulation of triglycerides in hepatocytes, which leads to hepatocellular carcinoma. MicroRNA 122 (MIR122) is expressed only in the liver, where it regulates lipid metabolism. We investigated the mechanism by which free fatty acids (FFAs) regulate MIR122 expression and the effect of MIR122 on triglyceride synthesis. We analyzed MIR122 promoter activity and validated its target mRNAs by transfection of Luciferase reporter plasmids into Huh7, BNL-1ME, and HEK293 cultured cell lines. We measured levels of microRNAs and mRNAs by quantitative real-time PCR analysis of RNA extracted from plasma, liver, muscle, and adipose tissues of C57BL/6 mice given the FFA-inducer CL316243. MIR122 was inhibited using an inhibitor of MIR122. Metabolic profiles of mice were determined using metabolic chambers and by histologic analyses of liver tissues. We performed RNA sequence analyses to identify metabolic pathways involving MIR122. We validated human Agpat1 and Dgat1 mRNAs, involved in triglyceride synthesis, as targets of MIR122. FFAs increased MIR122 expression in livers of mice by activating the retinoic acid-related orphan receptor alpha, and induced secretion of MIR122 from liver to blood. Circulating MIR122 entered muscle and adipose tissues of mice, reducing mRNA levels of genes involved in triglyceride synthesis. Mice injected with an inhibitor of MIR122 and then given CL316243, accumulated triglycerides in liver and muscle tissues, and had reduced rates of β-oxidation. There was a positive correlation between level of FFAs and level of MIR122 in plasma samples from 6 healthy individuals, collected before and during fasting. In biochemical and histologic studies of plasma, liver, muscle, and adipose tissues from mice, we found that FFAs increase hepatic expression and secretion of MIR122, which regulates energy storage vs expenditure in liver and peripheral tissues. Strategies to reduce

Exercise increases TBC1D1 phosphorylation in human skeletal muscle

Science.gov (United States)

Jessen, Niels; An, Ding; Lihn, Aina S.; Nygren, Jonas; Hirshman, Michael F.; Thorell, Anders

2011-01-01

Exercise and weight loss are cornerstones in the treatment and prevention of type 2 diabetes, and both interventions function to increase insulin sensitivity and glucose uptake into skeletal muscle. Studies in rodents demonstrate that the underlying mechanism for glucose uptake in muscle involves site-specific phosphorylation of the Rab-GTPase-activating proteins AS160 (TBC1D4) and TBC1D1. Multiple kinases, including Akt and AMPK, phosphorylate TBC1D1 and AS160 on distinct residues, regulating their activity and allowing for GLUT4 translocation. In contrast to extensive rodent-based studies, the regulation of AS160 and TBC1D1 in human skeletal muscle is not well understood. In this study, we determined the effects of dietary intervention and a single bout of exercise on TBC1D1 and AS160 site-specific phosphorylation in human skeletal muscle. Ten obese (BMI 33.4 ± 2.4, M-value 4.3 ± 0.5) subjects were studied at baseline and after a 2-wk dietary intervention. Muscle biopsies were obtained from the subjects in the resting (basal) state and immediately following a 30-min exercise bout (70% V̇o2 max). Muscle lysates were analyzed for AMPK activity and Akt phosphorylation and for TBC1D1 and AS160 phosphorylation on known or putative AMPK and Akt sites as follows: AS160 Ser711 (AMPK), TBC1D1 Ser231 (AMPK), TBC1D1 Ser660 (AMPK), TBC1D1 Ser700 (AMPK), and TBC1D1 Thr590 (Akt). The diet intervention that consisted of a major shift in the macronutrient composition resulted in a 4.2 ± 0.4 kg weight loss (P < 0.001) and a significant increase in insulin sensitivity (M value 5.6 ± 0.6), but surprisingly, there was no effect on expression or phosphorylation of any of the muscle-signaling proteins. Exercise increased muscle AMPKα2 activity but did not increase Akt phosphorylation. Exercise increased phosphorylation on AS160 Ser711, TBC1D1 Ser231, and TBC1D1 Ser660 but had no effect on TBC1D1 Ser700. Exercise did not increase TBC1D1 Thr590 phosphorylation or TBC1D1/AS160 PAS

Molecular aspects of glucose homeostasis in skeletal muscle--A focus on the molecular mechanisms of insulin resistance.

Science.gov (United States)

Carnagarin, Revathy; Dharmarajan, Arun M; Dass, Crispin R

2015-12-05

Among all the varied actions of insulin, regulation of glucose homeostasis is the most critical and intensively studied. With the availability of glucose from nutrient metabolism, insulin action in muscle results in increased glucose disposal via uptake from the circulation and storage of excess, thereby maintaining euglycemia. This major action of insulin is executed by redistribution of the glucose transporter protein, GLUT4 from intracellular storage sites to the plasma membrane and storage of glucose in the form of glycogen which also involves modulation of actin dynamics that govern trafficking of all the signal proteins of insulin signal transduction. The cellular mechanisms responsible for these trafficking events and the defects associated with insulin resistance are largely enigmatic, and this review provides a consolidated overview of the various molecular mechanisms involved in insulin-dependent glucose homeostasis in skeletal muscle, as insulin resistance at this major peripheral site impacts whole body glucose homeostasis. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Kinetics of glucose transport in rat muscle

DEFF Research Database (Denmark)

Ploug, Thorkil; Galbo, Henrik; Vinten, Jørgen

1987-01-01

The effects of insulin and prior muscle contractions, respectively, on 3-O-methylglucose (3-O-MG) transport in skeletal muscle were studied in the perfused rat hindquarter. Initial rates of entry of 3-O-MG in red gastrocnemius, soleus, and white gastrocnemius muscles as a function of perfusate 3-O-MG...... concentration exhibited Michaelis-Menten kinetics. Uptake by simple diffusion could not be detected. The maximum 3-O-MG transport velocity (Vmax) was increased more by maximum isometric contractions (10- to 40-fold, depending on fiber type) than by insulin (20,000 microU/ml; 3- to 20-fold) in both red and white...

Tyrosine glycosylation is involved in muscle-glycogen synthesis

International Nuclear Information System (INIS)

Rodriguez, I.R.; Tandecarz, J.S.; Kirkman, B.R.; Whelan, W.J.

1986-01-01

Rabbit-muscle glycogen contains a covalently bound protein having Mr 37,000 that the authors will henceforth refer to as glycogenin. It is completely insoluble in water at pH 5, and may be generated as a precipitate as a result of the combined action on glycogen of α-amylase and glucoamylase, or by treatment with anhydrous hydrogen fluoride. In the former case the protein still carries some of the glucose residues of glycogen (10-30 per mole of glycogenin). The linkage between glycogen and glycogenin has been identified as a novel glycosidic-amino acid bond. The authors demonstrated glucosylation with UDP[/sup 14/C]glucose by a muscle extract of two rabbit-muscle proteins contained in the same extract. The relation of these proteins to glycogenin, and whether the amino acid undergoing glucosylation is tyrosine, remains to be explored. The discovery of glycogenin is, the authors believe, an important clue to the mechanism of biogenesis of glycogen and may represent a previously unsuspected means of metabolic control of the glycogen content of the cell and the location of glycogen within the cell. The facts that the linkage between glycogen and glycogenin is via tyrosine, that insulin stimulates glycogen synthesis, and acts on its receptor by causing it to become an active tyrosine kinase, may be linked by a common thread

Muscles, exercise and obesity

DEFF Research Database (Denmark)

Pedersen, Bente K; Febbraio, Mark A

2012-01-01

During the past decade, skeletal muscle has been identified as a secretory organ. Accordingly, we have suggested that cytokines and other peptides that are produced, expressed and released by muscle fibres and exert either autocrine, paracrine or endocrine effects should be classified as myokines....... The finding that the muscle secretome consists of several hundred secreted peptides provides a conceptual basis and a whole new paradigm for understanding how muscles communicate with other organs, such as adipose tissue, liver, pancreas, bones and brain. However, some myokines exert their effects within...... the muscle itself. Thus, myostatin, LIF, IL-6 and IL-7 are involved in muscle hypertrophy and myogenesis, whereas BDNF and IL-6 are involved in AMPK-mediated fat oxidation. IL-6 also appears to have systemic effects on the liver, adipose tissue and the immune system, and mediates crosstalk between intestinal...

Obesity impairs skeletal muscle AMPK signaling during exercise: role of AMPKα2 in the regulation of exercise capacity in vivo.

Science.gov (United States)

Lee-Young, R S; Ayala, J E; Fueger, P T; Mayes, W H; Kang, L; Wasserman, D H

2011-07-01

Skeletal muscle AMP-activated protein kinase (AMPK)α2 activity is impaired in obese, insulin-resistant individuals during exercise. We determined whether this defect contributes to the metabolic dysregulation and reduced exercise capacity observed in the obese state. C57BL/6J wild-type (WT) mice and/or mice expressing a kinase dead AMPKα2 subunit in skeletal muscle (α2-KD) were fed chow or high-fat (HF) diets from 3 to 16 weeks of age. At 15 weeks, mice performed an exercise stress test to determine exercise capacity. In WT mice, muscle glucose uptake and skeletal muscle AMPKα2 activity was assessed in chronically catheterized mice (carotid artery/jugular vein) at 16 weeks. In a separate study, HF-fed WT and α2-KD mice performed 5 weeks of exercise training (from 15 to 20 weeks of age) to test whether AMPKα2 is necessary to restore work tolerance. HF-fed WT mice had reduced exercise tolerance during an exercise stress test, and an attenuation in muscle glucose uptake and AMPKα2 activity during a single bout of exercise (Pfeeding further reduced running time ∼25% (Pexercise training, HF-fed WT and α2-KD mice increased maximum running speed ∼35% (PExercise training restored running speed to levels seen in healthy, chow-fed mice. HF feeding impairs AMPKα2 activity in skeletal muscle during exercise in vivo. Although this defect directly contributes to reduced exercise capacity, findings in HF-fed α2-KD mice show that AMPKα2-independent mechanisms are also involved. Importantly, α2-KD mice on a HF-fed diet adapt to regular exercise by increasing exercise tolerance, demonstrating that this adaptation is independent of skeletal muscle AMPKα2 activity.

Measuring the serotonin uptake site using [3H]paroxetine--a new serotonin uptake inhibitor

International Nuclear Information System (INIS)

Gleiter, C.H.; Nutt, D.J.

1988-01-01

Serotonin is an important neurotransmitter that may be involved in ethanol preference and dependence. It is possible to label the serotonin uptake site in brain using the tricyclic antidepressant imipramine, but this also binds to other sites. We have used the new high-affinity uptake blocker paroxetine to define binding to this site and report it to have advantages over imipramine as a ligand

{sup 99m}Tc-sestamibi muscle scintigraphy to assess the response to neuromuscular electrical stimulation of normal quadriceps femoris muscle

Energy Technology Data Exchange (ETDEWEB)

Pekindil, Y.; Sarikaya, A.; Birtane, M.; Pekindil, G.; Salan, A. [Trakya Univ., Edirne (Turkey). Hospital

2001-08-01

Neuromuscular electrical stimulation (NMES) is widely used for improving muscle strength by simultaneous contraction in the prevention of muscle atrophy. Although there exist many clinical methods for evaluating the therapeutic response of muscles, {sup 99m}Tc-sestamibi which is a skeletal muscle perfusion and metabolism agent has not previously been used for this purpose. The aim of our work was to ascertain whether {sup 99m}Tc-sestamibi muscle scintigraphy is useful in the monitoring of therapeutic response to NMES in healthy women. The study included 16 women aged between 21 and 45, with a mean age of 32.7{+-}6.4. Both quadriceps femoris muscles (QFM) of each patient were studied. After randomization to remove the effect of the dominant side, one QFM of each patient was subjected to the NMES procedure for a period of 20 days. NMES was performed with an alternating biphasic rectangular current, from a computed electrical stimulator daily for 23 minutes. After measurement of skinfold thickness over the thigh, pre- and post-NMES girth measurements were assessed in centimeters. Sixty minutes after injections of 555 MBq {sup 99m}Tc-sestamibi, static images of the thigh were obtained for 5 minutes. The thigh-to-knee uptake ratio was calculated by semiquantitative analysis and normalized to body surface area (NUR=normalized uptake ratio). The difference between the pre and post NMES NUR values was significant (1.76{+-}0.31 versus 2.25{+-}0.38, p=0.0000). The percentage (%) increase in NUR values also well correlated with the % increase in thigh girth measurements (r=0.89, p=0.0000). These results indicated that {sup 99m}Tc-sestamibi muscle scintigraphy as a new tool may be useful in evaluating therapeutic response to NMES. (author)

Technetium-99m methylene diphosphonate uptake in the brachialis muscle hematoma in a patient with prostate cancer and coagulation disorder mimicking bone metastasis evaluated by single-photon emission tomography-computed tomography/computed tomography

Energy Technology Data Exchange (ETDEWEB)

Kamaleshwaran, Koramadai Karuppusamy; Mohanan, Vyshakh; Shinto, Ajit Sugunan, E-mail: dr.kamaleshwar@gmail.com [Department of Nuclear Medicine and PET/CT, Kovai Medical Centre and Hospital Limited, Coimbatore (India); Madhavan, Devdas [Department of Urology, Comprehensive Cancer Care Centre, Kovai Medical Centre and Hospital Limited, Coimbatore (India)

2013-10-15

We report a case of 79-year-old male with prostate cancer and coagulation disorder presented with left shoulder pain. He underwent bone scintigraphy to rule out metastasis, which showed intense foci of tracer activity in the left axilla. Hybrid single-photon emission tomography-computed tomography (SPECT/CT) of the shoulder region localized tracer uptake to the left brachialis muscle hematoma. (author)

Technetium-99m methylene diphosphonate uptake in the brachialis muscle hematoma in a patient with prostate cancer and coagulation disorder mimicking bone metastasis evaluated by single-photon emission tomography-computed tomography/computed tomography

International Nuclear Information System (INIS)

Kamaleshwaran, Koramadai Karuppusamy; Mohanan, Vyshakh; Shinto, Ajit Sugunan; Madhavan, Devdas

2013-01-01

We report a case of 79-year-old male with prostate cancer and coagulation disorder presented with left shoulder pain. He underwent bone scintigraphy to rule out metastasis, which showed intense foci of tracer activity in the left axilla. Hybrid single-photon emission tomography-computed tomography (SPECT/CT) of the shoulder region localized tracer uptake to the left brachialis muscle hematoma. (author)

Training-induced adaptation of oxidative phosphorylation in skeletal muscles.

OpenAIRE

Korzeniewski, Bernard; Zoladz, Jerzy A

2003-01-01

Muscle training/conditioning improves the adaptation of oxidative phosphorylation in skeletal muscles to physical exercise. However, the mechanisms underlying this adaptation are still not understood fully. By quantitative analysis of the existing experimental results, we show that training-induced acceleration of oxygen-uptake kinetics at the onset of exercise and improvement of ATP/ADP stability due to physical training are mainly caused by an increase in the amount of mitochondrial protein...

Alantolactone Improves Prolonged Exposure of Interleukin-6-Induced Skeletal Muscle Inflammation Associated Glucose Intolerance and Insulin Resistance

Directory of Open Access Journals (Sweden)

Minjee Kim

2017-06-01

Full Text Available The pro-inflammatory cytokine, Interleukin-6 (IL-6, has been proposed to be one of the mediators that link chronic inflammation to glucose intolerance and insulin resistance. Many studies have demonstrated the effects of IL-6 on insulin action in the skeletal muscle. However, few studies have investigated the effect of long-term treatment of IL-6, leading to glucose intolerance and insulin resistance. In the present study, we observed protective effects of alantolactone, a sesquiterpene lactone isolated from Inula helenium against glucose intolerance and insulin resistance induced by prolonged exposure of IL-6. Alantolactone has been reported to have anti-inflammatory and anti-cancer effects through IL-6-induced signal transducer and activator of transcription 3 (STAT3 signaling pathway. The relationship between IL-6 exposure and expression of toll-like receptor 4 (TLR4, involved in inflammation in the skeletal muscle, and the underlying mechanisms were investigated. We observed maximum dysregulation of glucose uptake after 40 ng/ml IL-6 induction for 24 h in L6 myotubes. Prolonged IL-6 exposure suppressed glucose uptake regulating alpha serine/threonine-protein kinase (AKT phosphorylation; however, pretreatment with alantolactone activated AKT phosphorylation and improved glucose uptake. Alantolactone also attenuated IL-6-stimulated STAT3 phosphorylation, followed by an increase in expression of negative regulator suppressor of cytokine signaling 3 (SOCS3. Furthermore, IL-6-induced expression of pathogen recognition receptor, TLR4, was also suppressed by alantolactone pretreatment. Post-silencing of STAT3 using siRNA approach, IL-6-stimulated siRNA-STAT3 improved glucose uptake and suppressed TLR4 gene expression. Taken together, we propose that, as a STAT3 inhibitor, alantolactone, improves glucose regulation in the skeletal muscle by inhibiting IL-6-induced STAT3-SOCS3 signaling followed by inhibition of the TLR4 gene expression. Therefore

Myofascial involvement of supra- and infraspinatus muscles contributes to ipsilateral shoulder pain after muscle-sparing thoracotomy and video-assisted thoracic surgery.

Science.gov (United States)

Ohmori, Aki; Iranami, Hiroshi; Fujii, Keisuke; Yamazaki, Akinori; Doko, Yukari

2013-12-01

This study examined the hypothesis that ipsilateral upper extremity elevation for muscle-sparing thoracotomy procedures contributes to the postoperative shoulder pain. Prospective observational study. Medical center. ASA physical status 1-2 patients undergoing elective lung surgeries including pneumonectomy, lobectomy, and segmentectomy performed through either the anterolateral approach or video-assisted thoracotomy surgery. Postoperative observation of ipsilateral shoulder pain. Postoperative examinations of sites of shoulder pain (clavicle, anterior, lateral,or posterior aspect of acromion, posterior neck, supraspinatus, infraspinatus, and these entire areas) with or without trigger points, visual analog scale score of wound pain, and requested counts of analgesics. The number of patients who suffered from postoperative shoulder pain was 37 of 70 (52.9%). Demographic data, anterolateral/VATS ratio, VAS scores, and requested counts of rescue analgesics requirement were similar in the groups of patients with and without postoperative shoulder pain. The segmentectomy caused a significantly higher incidence of postoperative shoulder pain compared with other procedures (p shoulder pain showed defined trigger points in their painful areas. These results supported the hypothesis that myofascial involvement contributed, to some extent, to shoulder pain after muscle-sparing thoracotomy with ipsilateral upper extremity elevation. Copyright © 2013 Elsevier Inc. All rights reserved.

Diselenolane-mediated cellular uptake.

Science.gov (United States)

Chuard, Nicolas; Poblador-Bahamonde, Amalia I; Zong, Lili; Bartolami, Eline; Hildebrandt, Jana; Weigand, Wolfgang; Sakai, Naomi; Matile, Stefan

2018-02-21

The emerging power of thiol-mediated uptake with strained disulfides called for a move from sulfur to selenium. We report that according to results with fluorescent model substrates, cellular uptake with 1,2-diselenolanes exceeds uptake with 1,2-dithiolanes and epidithiodiketopiperazines with regard to efficiency as well as intracellular localization. The diselenide analog of lipoic acid performs best. This 1,2-diselenolane delivers fluorophores efficiently to the cytosol of HeLa Kyoto cells, without detectable endosomal capture as with 1,2-dithiolanes or dominant escape into the nucleus as with epidithiodiketopiperazines. Diselenolane-mediated cytosolic delivery is non-toxic (MTT assay), sensitive to temperature but insensitive to inhibitors of endocytosis (chlorpromazine, methyl-β-cyclodextrin, wortmannin, cytochalasin B) and conventional thiol-mediated uptake (Ellman's reagent), and to serum. Selenophilicity, the extreme CSeSeC dihedral angle of 0° and the high but different acidity of primary and secondary selenols might all contribute to uptake. Thiol-exchange affinity chromatography is introduced as operational mimic of thiol-mediated uptake that provides, in combination with rate enhancement of DTT oxidation, direct experimental evidence for existence and nature of the involved selenosulfides.

Myoglobin plasma level related to muscle mass and fiber composition: a clinical marker of muscle wasting?

Science.gov (United States)

Weber, Marc-André; Kinscherf, Ralf; Krakowski-Roosen, Holger; Aulmann, Michael; Renk, Hanna; Künkele, Annette; Edler, Lutz; Kauczor, Hans-Ulrich; Hildebrandt, Wulf

2007-08-01

Progressive muscle wasting is a central feature of cancer-related cachexia and has been recognized as a determinant of poor prognosis and quality of life. However, until now, no easily assessable clinical marker exists that allows to predict or to track muscle wasting. The present study evaluated the potential of myoglobin (MG) plasma levels to indicate wasting of large locomotor muscles and, moreover, to reflect the loss of MG-rich fiber types, which are most relevant for daily performance. In 17 cancer-cachectic patients (weight loss 22%) and 27 age- and gender-matched healthy controls, we determined plasma levels of MG and creatine kinase (CK), maximal quadriceps muscle cross-sectional area (CSA) by magnetic resonance imaging, muscle morphology and fiber composition in biopsies from the vastus lateralis muscle, body cell mass (BCM) by impedance technique as well as maximal oxygen uptake (VO(2)max). In cachectic patients, plasma MG, muscle CSA, BCM, and VO(2)max were 30-35% below control levels. MG showed a significant positive correlation to total muscle CSA (r = 0.65, p max as an important functional readout. CK plasma levels appear to be less reliable because prolonged increases are observed in even subclinical myopathies or after exercise. Notably, cancer-related muscle wasting was not associated with increases in plasma MG or CK in this study.

Effect of Phenolic Compounds from Elderflowers on Glucose- and Fatty Acid Uptake in Human Myotubes and HepG2-Cells

Directory of Open Access Journals (Sweden)

Giang Thanh Thi Ho

2017-01-01

Full Text Available Type 2 diabetes (T2D is manifested by progressive metabolic impairments in tissues such as skeletal muscle and liver, and these tissues become less responsive to insulin, leading to hyperglycemia. In the present study, stimulation of glucose and oleic acid uptake by elderflower extracts, constituents and metabolites were tested in vitro using the HepG2 hepatocellular liver carcinoma cell line and human skeletal muscle cells. Among the crude extracts, the 96% EtOH extract showed the highest increase in glucose and oleic acid uptake in human skeletal muscle cells and HepG2-cells. The flavonoids and phenolic acids contained therein were potent stimulators of glucose and fatty acid uptake in a dose-dependent manner. Most of the phenolic constituents and several of the metabolites showed high antioxidant activity and showed considerably higher α-amylase and α-glucosidase inhibition than acarbose. Elderflower might therefore be valuable as a functional food against diabetes.

Partial neuromuscular blockade in humans enhances muscle blood flow during exercise independently of muscle oxygen uptake and acetylcholine receptor blockade

DEFF Research Database (Denmark)

Hellsten, Ylva; Krustrup, Peter; Iaia, F Marcello

2009-01-01

This study examined the role of acetylcholine for skeletal muscle blood flow during exercise by use of the competitive neuromuscular blocking agent cisatracurium in combination with the acetylcholine receptor blocker glycopyrrone. Nine healthy male subjects performed a 10-min bout of one-legged k......This study examined the role of acetylcholine for skeletal muscle blood flow during exercise by use of the competitive neuromuscular blocking agent cisatracurium in combination with the acetylcholine receptor blocker glycopyrrone. Nine healthy male subjects performed a 10-min bout of one...... conductance during exercise, events that are not associated with either acetylcholine or an increased oxygen demand. The results do not support an essential role for acetylcholine, released form the neuromuscular junction, in exercise hyperaemia or for the enhanced blood flow during neuromuscular blockade....... The enhanced exercise hyperemia during partial neuromuscular blockade may be related to a greater recruitment of fast-twitch muscle fibres. Key words: blood flow, neuromuscular blockade, exercise, skeletal muscle....

Locomotor Muscle Fatigue Does Not Alter Oxygen Uptake Kinetics during High-Intensity Exercise.

Science.gov (United States)

Hopker, James G; Caporaso, Giuseppe; Azzalin, Andrea; Carpenter, Roger; Marcora, Samuele M

2016-01-01

The [Formula: see text] slow component ([Formula: see text]) that develops during high-intensity aerobic exercise is thought to be strongly associated with locomotor muscle fatigue. We sought to experimentally test this hypothesis by pre-fatiguing the locomotor muscles used during subsequent high-intensity cycling exercise. Over two separate visits, eight healthy male participants were asked to either perform a non-metabolically stressful 100 intermittent drop-jumps protocol (pre-fatigue condition) or rest for 33 min (control condition) according to a random and counterbalanced order. Locomotor muscle fatigue was quantified with 6-s maximal sprints at a fixed pedaling cadence of 90 rev·min -1 . Oxygen kinetics and other responses (heart rate, capillary blood lactate concentration and rating of perceived exertion, RPE) were measured during two subsequent bouts of 6 min cycling exercise at 50% of the delta between the lactate threshold and [Formula: see text] determined during a preliminary incremental exercise test. All tests were performed on the same cycle ergometer. Despite significant locomotor muscle fatigue ( P = 0.03), the [Formula: see text] was not significantly different between the pre-fatigue (464 ± 301 mL·min -1 ) and the control (556 ± 223 mL·min -1 ) condition ( P = 0.50). Blood lactate response was not significantly different between conditions ( P = 0.48) but RPE was significantly higher following the pre-fatiguing exercise protocol compared with the control condition ( P locomotor muscle fatigue does not significantly alter the [Formula: see text] kinetic response to high intensity aerobic exercise, and challenge the hypothesis that the [Formula: see text] is strongly associated with locomotor muscle fatigue.

Gestational Undernourishment Modifies the Composition of Skeletal Muscle Transverse Tubule Membranes and the Mechanical Properties of Muscles in Newborn Rats

Directory of Open Access Journals (Sweden)

Ricardo Tonathiu Ramírez-Oseguera

2013-10-01

Full Text Available Backgroud/Aims: Skeletal muscle (SM constitutes more than 40% of the body weight in adulthood. Transports dietary glucose mainly through the insulin-dependent glucose transporter (Glut-4 located in the Transverse tubule membrane system (TT. The TT development ends shortly after birth. The TT membrane hosts the proteins involved in excitation-contraction coupling and glucose uptake. Glycaemic regulation through movement is a key function of fully developed skeletal muscle. In this study, we aimed to characterize the effect of gestational undernourishment (GUN in rats GLUT-4 expression and on the protein/lipid content of the TT membranes. We also examined the effect of GUN on the mechanical properties of muscles as an indication of the metabolic condition of the SM at birth. Methods: Isolated TT membrane from SM of GUN rats were used to study lipid/protein content and protein stability by differential scanning calorimetry. The effect of GUN on the SM mechanical properties was determined in isolated Extensor Digitorum Longus (EDL muscle. Results: We demonstrate that compared to control, GUN in the new-born produces; i decreases body weight; ii diminution in SM mass; iii decreases the formation of TT membranes; iv expresses TT membrane proteins with higher thermal stability. The TT membrane expression of GLUT-4 in GUN offspring was twice that of controls. The isolated EDL of GUN offspring was 20% stronger as measured by contractile force and more resistant to fatigue relative to controls. Conclusion; These results provide the first evidence of adaptive changes of the SM in new-borns exposed to severe gestational food restriction. The effects of GUN on muscle at birth are the first step toward detrimental SM metabolic function, contributing to the physiopathology of metabolic diseases in adulthood.

Gestational undernourishment modifies the composition of skeletal muscle transverse tubule membranes and the mechanical properties of muscles in newborn rats.

Science.gov (United States)

Ramírez-Oseguera, Ricardo Tonathiu; Jiménez-Garduño, Aura Matilde; Alvarez, Rocío; Heine, Katharina; Pinzón-Estrada, Enrique; Torres-Saldaña, Ismael; Ortega, Alicia

2013-01-01

[corrected] Skeletal muscle (SM) constitutes more than 40% of the body weight in adulthood. Transports dietary glucose mainly through the insulin-dependent glucose transporter (Glut-4) located in the Transverse tubule membrane system (TT). The TT development ends shortly after birth. The TT membrane hosts the proteins involved in excitation-contraction coupling and glucose uptake. Glycaemic regulation through movement is a key function of fully developed skeletal muscle. In this study, we aimed to characterize the effect of gestational undernourishment (GUN) in rats GLUT-4 expression and on the protein/lipid content of the TT membranes. We also examined the effect of GUN on the mechanical properties of muscles as an indication of the metabolic condition of the SM at birth. Isolated TT membrane from SM of GUN rats were used to study lipid/protein content and protein stability by differential scanning calorimetry. The effect of GUN on the SM mechanical properties was determined in isolated Extensor Digitorum Longus (EDL) muscle. We demonstrate that compared to control, GUN in the new-born produces; i) decreases body weight; ii) diminution in SM mass; iii) decreases the formation of TT membranes; iv) expresses TT membrane proteins with higher thermal stability. The TT membrane expression of GLUT-4 in GUN offspring was twice that of controls. The isolated EDL of GUN offspring was 20% stronger as measured by contractile force and more resistant to fatigue relative to controls. These results provide the first evidence of adaptive changes of the SM in new-borns exposed to severe gestational food restriction. The effects of GUN on muscle at birth are the first step toward detrimental SM metabolic function, contributing to the physiopathology of metabolic diseases in adulthood. © 2013 S. Karger AG, Basel

Changes in muscle strength and morphology after muscle unloading in Special Forces missions

DEFF Research Database (Denmark)

Thorlund, J B; Jakobsen, O; Madsen, T

2011-01-01

The purpose of the present study was to determine the changes in maximal muscle strength, rapid force capacity, jumping performance and muscle morphology following a Special Forces military operation involving 8 days of muscle unloading. Nine male Special Forces soldiers were tested before (pre) ...

Na+,K+-pump stimulation improves contractility in isolated muscles of mice with hyperkalemic periodic paralysis.

Science.gov (United States)

Clausen, Torben; Nielsen, Ole Bækgaard; Clausen, Johannes D; Pedersen, Thomas Holm; Hayward, Lawrence J

2011-07-01

In patients with hyperkalemic periodic paralysis (HyperKPP), attacks of muscle weakness or paralysis are triggered by K(+) ingestion or rest after exercise. Force can be restored by muscle work or treatment with β(2)-adrenoceptor agonists. A missense substitution corresponding to a mutation in the skeletal muscle voltage-gated Na(+) channel (Na(v)1.4, Met1592Val) causing human HyperKPP was targeted into the mouse SCN4A gene (mutants). In soleus muscles prepared from these mutant mice, twitch, tetanic force, and endurance were markedly reduced compared with soleus from wild type (WT), reflecting impaired excitability. In mutant soleus, contractility was considerably more sensitive than WT soleus to inhibition by elevated [K(+)](o). In resting mutant soleus, tetrodotoxin (TTX)-suppressible (22)Na uptake and [Na(+)](i) were increased by 470 and 58%, respectively, and membrane potential was depolarized (by 16 mV, P Na(+),K(+) pump-mediated (86)Rb uptake was 83% larger than in WT. Salbutamol stimulated (86)Rb uptake and reduced [Na(+)](i) both in mutant and WT soleus. Stimulating Na(+),K(+) pumps with salbutamol restored force in mutant soleus and extensor digitorum longus (EDL). Increasing [Na(+)](i) with monensin also restored force in soleus. In soleus, EDL, and tibialis anterior muscles of mutant mice, the content of Na(+),K(+) pumps was 28, 62, and 33% higher than in WT, respectively, possibly reflecting the stimulating effect of elevated [Na(+)](i) on the synthesis of Na(+),K(+) pumps. The results confirm that the functional disorders of skeletal muscles in HyperKPP are secondary to increased Na(+) influx and show that contractility can be restored by acute stimulation of the Na(+),K(+) pumps. Calcitonin gene-related peptide (CGRP) restored force in mutant soleus but caused no detectable increase in (86)Rb uptake. Repeated excitation and capsaicin also restored contractility, possibly because of the release of endogenous CGRP from nerve endings in the isolated

Peripheral endocannabinoids regulate skeletal muscle development and maintenance

Directory of Open Access Journals (Sweden)

Dongjiao Zhao

2010-12-01

Full Text Available As a principal tissue responsible for insulin-mediated glucose uptake, skeletal muscle is important for whole-body health. The role of peripheral endocannabinoids as regulators of skeletal muscle metabolism has recently gained a lot of interest, as endocannabinoid system disorders could cause peripheral insulin resistance. We investigated the role of the peripheral endocannabinoid system in skeletal muscle development and maintenance. Cultures of C2C12 cells, primary satellite cells and mouse skeletal muscle single fibers were used as model systems for our studies. We found an increase in cannabinoid receptor type 1 (CB1 mRNA and endocannabinoid synthetic enzyme mRNA skeletal muscle cells during differentiation. We also found that activation of CB1 inhibited myoblast differentiation, expanded the number of satellite cells, and stimulated the fast-muscle oxidative phenotype. Our findings contribute to understanding of the role of the endocannabinoid system in skeletal muscle metabolism and muscle oxygen consumption, and also help to explain the effects of the peripheral endocannabinoid system on whole-body energy balance.

Uptake of phenolic compounds from plant foods in human intestinal ...

Indian Academy of Sciences (India)

Gavirangappa Hithamani

Open-pan boiling reduced the uptake of quercetin from the onion. Among pure phenolic ... vegetable, is a major source of flavonoid in the diet (Galdón et al. 2008). ..... inflammatory and anti-atherosclerotic properties of red wine polyphenolic ... quercetin and quercetin-rich red onion extract on skeletal muscle mitochondria ...

Protein kinase N2 regulates AMP kinase signaling and insulin responsiveness of glucose metabolism in skeletal muscle.

Science.gov (United States)

Ruby, Maxwell A; Riedl, Isabelle; Massart, Julie; Åhlin, Marcus; Zierath, Juleen R

2017-10-01

Insulin resistance is central to the development of type 2 diabetes and related metabolic disorders. Because skeletal muscle is responsible for the majority of whole body insulin-stimulated glucose uptake, regulation of glucose metabolism in this tissue is of particular importance. Although Rho GTPases and many of their affecters influence skeletal muscle metabolism, there is a paucity of information on the protein kinase N (PKN) family of serine/threonine protein kinases. We investigated the impact of PKN2 on insulin signaling and glucose metabolism in primary human skeletal muscle cells in vitro and mouse tibialis anterior muscle in vivo. PKN2 knockdown in vitro decreased insulin-stimulated glucose uptake, incorporation into glycogen, and oxidation. PKN2 siRNA increased 5'-adenosine monophosphate-activated protein kinase (AMPK) signaling while stimulating fatty acid oxidation and incorporation into triglycerides and decreasing protein synthesis. At the transcriptional level, PKN2 knockdown increased expression of PGC-1α and SREBP-1c and their target genes. In mature skeletal muscle, in vivo PKN2 knockdown decreased glucose uptake and increased AMPK phosphorylation. Thus, PKN2 alters key signaling pathways and transcriptional networks to regulate glucose and lipid metabolism. Identification of PKN2 as a novel regulator of insulin and AMPK signaling may provide an avenue for manipulation of skeletal muscle metabolism. Copyright © 2017 the American Physiological Society.

Reduced levels of skeletal muscle Na+K+ -ATPase in McArdle disease

Science.gov (United States)

Haller, R. G.; Clausen, T.; Vissing, J.; Blomqvist, C. G. (Principal Investigator)

1998-01-01

We evaluated the hypothesis that impaired sarcolemmal function associated with exaggerated potassium release, impaired potassium uptake, or both may contribute to exertional fatigue and abnormal circulatory responses to exercise in McArdle disease (MD). The cellular mechanism of exertional fatigue and muscle injury in MD is unknown but likely involves impaired function of the ATPases that couple ATP hydrolysis to cellular work, including the muscle sodium potassium pump (Na+K+-ATPase). However, the concentration of muscle Na+K+ pumps in MD is not known, and no studies have related exercise increases in blood potassium concentrations to muscle Na+K+ pump levels. We measured muscle Na+K+ pumps (3H-ouabain binding) and plasma K+ in response to 20 minutes of cycle exercise in six patients with MD and in six sex-, age-, and weight-matched sedentary individuals. MD patients had lower levels of 3H-ouabain binding (231 +/- 18 pmol/g w.w., mean +/- SD, range, 210 to 251) than control subjects (317 +/- 37, range, 266 to 371, p Na+K+ pump levels are low in MD patients compared with healthy subjects and identify a limitation of potassium reuptake that could result in sarcolemmal failure during peak rates of membrane activation and may promote exaggerated potassium-activated circulatory responses to submaximal exercise. The mechanism of the low Na+K+ pump concentrations in MD is unknown but may relate to deconditioning or to disruption of a close functional relationship between membrane ion transport and glycolysis.

Cellular fatty acid transport in heart and skeletal muscle as facilitated by proteins

NARCIS (Netherlands)

Luiken, J. J.; Schaap, F. G.; van Nieuwenhoven, F. A.; van der Vusse, G. J.; Bonen, A.; Glatz, J. F.

1999-01-01

Despite the importance of long-chain fatty acids (FA) as fuels for heart and skeletal muscles, the mechanism of their cellular uptake has not yet been clarified. There is dispute as to whether FA are taken up by the muscle cells via passive diffusion and/or carrier-mediated transport. Kinetic

The chemokine and scavenger receptor CXCL16/SR-PSOX is expressed in human vascular smooth muscle cells and is induced by interferon γ

International Nuclear Information System (INIS)

Wagsaeter, Dick; Olofsson, Peder S.; Norgren, Lars; Stenberg, Bjoern; Sirsjoe, Allan

2004-01-01

Atherosclerosis is an inflammatory disease that is characterised by the involvement of chemokines that are important for the recruitment of leukocytes and scavenger receptors that mediate foam cell formation. Several cytokines are involved in the regulation of chemokines and scavenger receptors in atherosclerosis. CXCL16 is a chemokine and scavenger receptor and found in macrophages in human atherosclerotic lesions. Using double-labelled immunohistochemistry, we identified that smooth muscle cells in human lesions express CXCL16. We then analysed the effects of IFN-γ, TNF-α, IL-12, IL-15, IL-18, and LPS on CXCL16 expression in cultured aortic smooth muscle cells. IFN-γ was the most potent CXCL16 inducer and increased mRNA, soluble form, membrane form, and total cellular levels of CXCL16. The IFN-γ induction of CXCL16 was also associated with increased uptake of oxLDL into these cells. Taken together, smooth muscle cells express CXCL16 in atherosclerotic lesions, which may play a role in the attraction of T cells to atherosclerotic lesions and contribute to the cellular internalisation of modified LDL

Muscle MRI in neutral lipid storage disease (NLSD).

Science.gov (United States)

Garibaldi, Matteo; Tasca, Giorgio; Diaz-Manera, Jordi; Ottaviani, Pierfancesco; Laschena, Francesco; Pantoli, Donatella; Gerevini, Simonetta; Fiorillo, Chiara; Maggi, Lorenzo; Tasca, Elisabetta; D'Amico, Adele; Musumeci, Olimpia; Toscano, Antonio; Bruno, Claudio; Massa, Roberto; Angelini, Corrado; Bertini, Enrico; Antonini, Giovanni; Pennisi, Elena Maria

2017-07-01

Neutral lipid storage disease (NLSD) is a rare inherited disorder of lipid metabolism resulting in lipid droplets accumulation in different tissues. Skeletal muscle could be affected in both two different form of disease: NLSD with myopathy (NLSD-M) and NLSD with ichthyosis (NLSD-I). We present the muscle imaging data of 12 patients from the Italian Network for NLSD: ten patients presenting NLSD-M and two patients with NLSD-I. In NLSD-M gluteus minimus, semimembranosus, soleus and gastrocnemius medialis in the lower limbs and infraspinatus in the upper limbs were the most affected muscles. Gracilis, sartorius, subscapularis, pectoralis, triceps brachii and sternocleidomastoid were spared. Muscle involvement was not homogenous and characteristic "patchy" replacement was observed in at least one muscle in all the patients. Half of the patients showed one or more STIR positive muscles. In both NLSD-I cases muscle involvement was not observed by T1-TSE sequences, but one of them showed positive STIR images in more than one muscle in the leg. Our data provides evidence that muscle imaging can identify characteristic alterations in NLSD-M, characterized by a specific pattern of muscle involvement with "patchy" areas of fatty replacement. Larger cohorts are needed to assess if a distinct pattern of muscle involvement exists also for NLSD-I.

Ethanol Exposure Causes Muscle Degeneration in Zebrafish

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Elizabeth C. Coffey

2018-03-01

Full Text Available Alcoholic myopathies are characterized by neuromusculoskeletal symptoms such as compromised movement and weakness. Although these symptoms have been attributed to neurological damage, EtOH may also target skeletal muscle. EtOH exposure during zebrafish primary muscle development or adulthood results in smaller muscle fibers. However, the effects of EtOH exposure on skeletal muscle during the growth period that follows primary muscle development are not well understood. We determined the effects of EtOH exposure on muscle during this phase of development. Strikingly, muscle fibers at this stage are acutely sensitive to EtOH treatment: EtOH induces muscle degeneration. The severity of EtOH-induced muscle damage varies but muscle becomes more refractory to EtOH as muscle develops. NF-kB induction in muscle indicates that EtOH triggers a pro-inflammatory response. EtOH-induced muscle damage is p53-independent. Uptake of Evans blue dye shows that EtOH treatment causes sarcolemmal instability before muscle fiber detachment. Dystrophin-null sapje mutant zebrafish also exhibit sarcolemmal instability. We tested whether Trichostatin A (TSA, which reduces muscle degeneration in sapje mutants, would affect EtOH-treated zebrafish. We found that TSA and EtOH are a lethal combination. EtOH does, however, exacerbate muscle degeneration in sapje mutants. EtOH also disrupts adhesion of muscle fibers to their extracellular matrix at the myotendinous junction: some detached muscle fibers retain beta-Dystroglycan indicating failure of muscle end attachments. Overexpression of Paxillin, which reduces muscle degeneration in zebrafish deficient for beta-Dystroglycan, is not sufficient to rescue degeneration. Taken together, our results suggest that EtOH exposure has pleiotropic deleterious effects on skeletal muscle.

Deletion of skeletal muscle SOCS3 prevents insulin resistance in obesity

DEFF Research Database (Denmark)

Beck Jørgensen, Sebastian; O'Neill, Hayley M; Sylow, Lykke

2013-01-01

Obesity is associated with chronic low-grade inflammation that contributes to defects in energy metabolism and insulin resistance. Suppressor of cytokine signaling (SOCS)-3 expression is increased in skeletal muscle of obese humans. SOCS3 inhibits leptin signaling in the hypothalamus and insulin...... of hyperinsulinemia and insulin resistance because of enhanced skeletal muscle insulin receptor substrate 1 (IRS1) and Akt phosphorylation that resulted in increased skeletal muscle glucose uptake. These data indicate that skeletal muscle SOCS3 does not play a critical role in regulating muscle development or energy...... expenditure, but it is an important contributing factor for inhibiting insulin sensitivity in obesity. Therapies aimed at inhibiting SOCS3 in skeletal muscle may be effective in reversing obesity-related glucose intolerance and insulin resistance....

Enhanced muscle insulin sensitivity after contraction/exercise is mediated by AMPK

DEFF Research Database (Denmark)

Kjøbsted, Rasmus; Munk-Hansen, Nanna; Birk, Jesper Bratz

2017-01-01

muscle and whole body insulin sensitivity in wild type (WT) mice, respectively. These effects were not found in AMPKα1α2 muscle-specific knockout mice. Prior in situ contraction did not increase insulin sensitivity in m. soleus from either genotype. Improvement in muscle insulin sensitivity....... Collectively, our data suggest that the AMPK-TBC1D4 signaling axis is likely mediating the improved muscle insulin sensitivity after contraction/exercise and illuminates an important and physiological relevant role of AMPK in skeletal muscle.......Earlier studies have demonstrated that muscle insulin sensitivity to stimulate glucose uptake is enhanced several hours after an acute bout of exercise. Using 5-aminoimidazole-4-carboxamide-ribonucleotide (AICAR), we recently demonstrated that prior activation of AMPK is sufficient to increase...

A Novel EPO Receptor Agonist Improves Glucose Tolerance via Glucose Uptake in Skeletal Muscle in a Mouse Model of Diabetes

Directory of Open Access Journals (Sweden)

Michael S. Scully

2011-01-01

Full Text Available Patients treated with recombinant human Epo demonstrate an improvement in insulin sensitivity. We aimed to investigate whether CNTO 530, a novel Epo receptor agonist, could affect glucose tolerance and insulin sensitivity. A single administration of CNTO 530 significantly and dose-dependently reduced the area under the curve in a glucose tolerance test in diet-induced obese and diabetic mice after 14, 21, and 28 days. HOMA analysis suggested an improvement in insulin sensitivity, and this effect was confirmed by a hyperinsulinemic-euglycemic clamp. Uptake of 14C-2-deoxy-D-glucose indicated that animals dosed with CNTO 530 transported more glucose into skeletal muscle and heart relative to control animals. In conclusion, CNTO530 has a profound effect on glucose tolerance in insulin-resistant rodents likely because of improving peripheral insulin sensitivity. This effect was observed with epoetin-α and darbepoetin-α, suggesting this is a class effect, but the effect with these compounds relative to CNTO530 was decreased in duration and magnitude.

Hypophosphatemia promotes lower rates of muscle ATP synthesis

DEFF Research Database (Denmark)

Pesta, Dominik H; Tsirigotis, Dimitrios N; Befroy, Douglas E

2016-01-01

. Rates of VATP normalized in both hypophosphatemic groups after restoring plasma Pi concentrations. Furthermore, VATP was directly related to cellular and mitochondrial Pi uptake in L6 and RC13 rodent myocytes and isolated muscle mitochondria. Similar findings were observed in a patient with chronic...

Anesthesia with propofol induces insulin resistance systemically in skeletal and cardiac muscles and liver of rats

Energy Technology Data Exchange (ETDEWEB)

Yasuda, Yoshikazu; Fukushima, Yuji; Kaneki, Masao [Department of Anaesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Shriners Hospitals for Children, Harvard Medical School, Boston, MA 02114 (United States); Martyn, J.A. Jeevendra, E-mail: jmartyn@partners.org [Department of Anaesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Shriners Hospitals for Children, Harvard Medical School, Boston, MA 02114 (United States)

2013-02-01

Highlights: ► Propofol, as a model anesthetic drug, induced whole body insulin resistance. ► Propofol anesthesia decreased glucose infusion rate to maintain euglycemia. ► Propofol decreased insulin-mediated glucose uptake in skeletal and cardiac muscles. ► Propofol increased hepatic glucose output confirming hepatic insulin resistance. -- Abstract: Hyperglycemia together with hepatic and muscle insulin resistance are common features in critically ill patients, and these changes are associated with enhanced inflammatory response, increased susceptibility to infection, muscle wasting, and worsened prognosis. Tight blood glucose control by intensive insulin treatment may reduce the morbidity and mortality in intensive care units. Although some anesthetics have been shown to cause insulin resistance, it remains unknown how and in which tissues insulin resistance is induced by anesthetics. Moreover, the effects of propofol, a clinically relevant intravenous anesthetic, also used in the intensive care unit for sedation, on insulin sensitivity have not yet been investigated. Euglycemic hyperinsulinemic clamp study was performed in rats anesthetized with propofol and conscious unrestrained rats. To evaluate glucose uptake in tissues and hepatic glucose output [{sup 3}H]glucose and 2-deoxy[{sup 14}C]glucose were infused during the clamp study. Anesthesia with propofol induced a marked whole-body insulin resistance compared with conscious rats, as reflected by significantly decreased glucose infusion rate to maintain euglycemia. Insulin-stimulated tissue glucose uptake was decreased in skeletal muscle and heart, and hepatic glucose output was increased in propofol anesthetized rats. Anesthesia with propofol induces systemic insulin resistance along with decreases in insulin-stimulated glucose uptake in skeletal and heart muscle and attenuation of the insulin-mediated suppression of hepatic glucose output in rats.

Anesthesia with propofol induces insulin resistance systemically in skeletal and cardiac muscles and liver of rats

International Nuclear Information System (INIS)

Yasuda, Yoshikazu; Fukushima, Yuji; Kaneki, Masao; Martyn, J.A. Jeevendra

2013-01-01

Highlights: ► Propofol, as a model anesthetic drug, induced whole body insulin resistance. ► Propofol anesthesia decreased glucose infusion rate to maintain euglycemia. ► Propofol decreased insulin-mediated glucose uptake in skeletal and cardiac muscles. ► Propofol increased hepatic glucose output confirming hepatic insulin resistance. -- Abstract: Hyperglycemia together with hepatic and muscle insulin resistance are common features in critically ill patients, and these changes are associated with enhanced inflammatory response, increased susceptibility to infection, muscle wasting, and worsened prognosis. Tight blood glucose control by intensive insulin treatment may reduce the morbidity and mortality in intensive care units. Although some anesthetics have been shown to cause insulin resistance, it remains unknown how and in which tissues insulin resistance is induced by anesthetics. Moreover, the effects of propofol, a clinically relevant intravenous anesthetic, also used in the intensive care unit for sedation, on insulin sensitivity have not yet been investigated. Euglycemic hyperinsulinemic clamp study was performed in rats anesthetized with propofol and conscious unrestrained rats. To evaluate glucose uptake in tissues and hepatic glucose output [ 3 H]glucose and 2-deoxy[ 14 C]glucose were infused during the clamp study. Anesthesia with propofol induced a marked whole-body insulin resistance compared with conscious rats, as reflected by significantly decreased glucose infusion rate to maintain euglycemia. Insulin-stimulated tissue glucose uptake was decreased in skeletal muscle and heart, and hepatic glucose output was increased in propofol anesthetized rats. Anesthesia with propofol induces systemic insulin resistance along with decreases in insulin-stimulated glucose uptake in skeletal and heart muscle and attenuation of the insulin-mediated suppression of hepatic glucose output in rats

Thyroid Scan and Uptake

Medline Plus

Full Text Available ... A thyroid scan is a type of nuclear medicine imaging. The radioactive iodine uptake test (RAIU) is ... thyroid function, but does not involve imaging. Nuclear medicine is a branch of medical imaging that uses ...

Regulation of exercise-induced lipid metabolism in skeletal muscle

DEFF Research Database (Denmark)

Jordy, Andreas Børsting; Kiens, Bente

2014-01-01

Exercise increases the utilization of lipids in muscle. The sources of lipids are long-chain fatty acids taken up from the plasma and fatty acids released from stores of intramuscular triacylglycerol by the action of intramuscular lipases. In the present review, we focus on the role of fatty acid...... binding proteins, particularly fatty acid translocase/cluster of differentiation 36 (FAT/CD36), in the exercise- and contraction-induced increase in uptake of long-chain fatty acids in muscle. The FAT/CD36 translocates from intracellular depots to the surface membrane upon initiation of exercise/muscle...... triglyceride lipase in regulation of muscle lipolysis. Although the molecular regulation of the lipases in muscle is not understood, it is speculated that intramuscular lipolysis may be regulated in part by the availability of the plasma concentration of long-chain fatty acids....

Single muscle fiber adaptations with marathon training.

Science.gov (United States)

Trappe, Scott; Harber, Matthew; Creer, Andrew; Gallagher, Philip; Slivka, Dustin; Minchev, Kiril; Whitsett, David

2006-09-01

The purpose of this investigation was to characterize the effects of marathon training on single muscle fiber contractile function in a group of recreational runners. Muscle biopsies were obtained from the gastrocnemius muscle of seven individuals (22 +/- 1 yr, 177 +/- 3 cm, and 68 +/- 2 kg) before, after 13 wk of run training, and after 3 wk of taper. Slow-twitch myosin heavy chain [(MHC) I] and fast-twitch (MHC IIa) muscle fibers were analyzed for size, strength (P(o)), speed (V(o)), and power. The run training program led to the successful completion of a marathon (range 3 h 56 min to 5 h 35 min). Oxygen uptake during submaximal running and citrate synthase activity were improved (P training program. Muscle fiber size declined (P training. P(o) was maintained in both fiber types with training and increased (P 60% increase (P training and was unchanged in MHC IIa fibers. Peak power increased (P training with a further increase (P marathon training decreased slow-twitch and fast-twitch muscle fiber size but that it maintained or improved the functional profile of these fibers. A taper period before the marathon further improved the functional profile of the muscle, which was targeted to the fast-twitch muscle fibers.

Direct evidence of fiber type-dependent GLUT-4 expression in human skeletal muscle

DEFF Research Database (Denmark)

Gaster, M; Poulsen, P; Handberg, A

2000-01-01

GLUT-4 expression in individual fibers of human skeletal muscles in younger and older adults was studied. Furthermore, the dependency of insulin-stimulated glucose uptake on fiber type distribution was investigated. Fiber type distribution was determined in cryosections of muscle biopsies from 8...... of slow fibers in the young (r = -0.45, P > 0.25) or in the elderly (r = 0. 11, P > 0.75) subjects. In conclusion, in human skeletal muscle, GLUT-4 expression is fiber type dependent and decreases with age, particularly in fast muscle fibers....

Patterns of arm muscle activation involved in octopus reaching movements.

Science.gov (United States)

Gutfreund, Y; Flash, T; Fiorito, G; Hochner, B

1998-08-01

The extreme flexibility of the octopus arm allows it to perform many different movements, yet octopuses reach toward a target in a stereotyped manner using a basic invariant motor structure: a bend traveling from the base of the arm toward the tip (Gutfreund et al., 1996a). To study the neuronal control of these movements, arm muscle activation [electromyogram (EMG)] was measured together with the kinematics of reaching movements. The traveling bend is associated with a propagating wave of muscle activation, with maximal muscle activation slightly preceding the traveling bend. Tonic activation was occasionally maintained afterward. Correlation of the EMG signals with the kinematic variables (velocities and accelerations) reveals that a significant part of the kinematic variability can be explained by the level of muscle activation. Furthermore, the EMG level measured during the initial stages of movement predicts the peak velocity attained toward the end of the reaching movement. These results suggest that feed-forward motor commands play an important role in the control of movement velocity and that simple adjustment of the excitation levels at the initial stages of the movement can set the velocity profile of the whole movement. A simple model of octopus arm extension is proposed in which the driving force is set initially and is then decreased in proportion to arm diameter at the bend. The model qualitatively reproduces the typical velocity profiles of octopus reaching movements, suggesting a simple control mechanism for bend propagation in the octopus arm.

Thyroid Scan and Uptake

Medline Plus

Full Text Available ... information about your thyroid’s size, shape, position and function that is often unattainable using other imaging procedures. ... thyroid uptake. It is a measurement of thyroid function, but does not involve imaging. Nuclear medicine is ...

Technetium-99m labeled 1-(4-fluorobenzyl)-4-(2-mercapto-2-methyl-4-azapentyl)-4- (2-mercapto-2-methylp ropylamino)-piperidine and iodine-123 metaiodobenzylguanidine for studying cardiac adrenergic function: a comparison of the uptake characteristics in vascular smooth muscle cells and neonatal cardiac myocytes, and an investigation in rats

International Nuclear Information System (INIS)

Samnick, Samuel; Scheuer, Claudia; Muenks, Sven; El-Gibaly, Amr M.; Menger, Michael D.; Kirsch, Carl-Martin

2004-01-01

In developing technetium-99m-based radioligands for in vivo studies of cardiac adrenergic neurons, we compared the uptake characteristics of the 99m Tc-labeled 1-(4-fluorobenzyl)-4-(2-mercapto-2-methyl-4-azapentyl)-4- (2-mercapto-2-methylpropylamino)-piperidine ( 99m Tc-FBPBAT) with those of the clinically established meta-[ 123 I]iodobenzylguanidine ( 123 I-MIBG) in rat vascular smooth muscle cells and neonatal cardiac myocytes. Furthermore, the cardiac and extracardiac uptake of both radiopharmaceuticals was assessed in intact rats and in rats pretreated with various α- and β-adrenoceptor drugs, and adrenergic reuptake blocking agents. The uptake of 99m Tc-FBPBAT and 123 I-MIBG into vascular smooth muscle cells and neonatal cardiac myocytes was rapid; more than 85% of the radioactivity accumulation into the cells occurring within the first 3 minutes. Radioactivity uptake after a 60-minute incubation at 37 degree sign C (pH 7.4) varied from 15% to 65% of the total loaded activity per million cells. In all cases, 99m Tc-FBPBAT showed the higher uptake, relative to 123 I-MIBG, at any given cell concentration. The cellular uptake of 99m Tc-FBPBAT was lower at 4 degree sign C and 20 degree sign C than at 37 degree sign C. In contrast, the 123 I-MIBG uptake was only slightly temperature dependent. Inhibition experiments confirmed that the cellular uptake of 123 I-MIBG is mediated by the uptake-I carrier, whereas α 1 - and β 1 -adrenoceptors were predominantly involved in the uptake of 99m Tc-FBPBAT into the cardiovascular tissues. Biodistribution studies in rats showed that 99m Tc-FBPBAT accumulated in myocardium after intravenous injection. Radioactivity in rat heart amounted to 2.32% and 1.91% of the injected dose per gram at 15 and 60 minutes postinjection, compared with 3.10% and 2.21% injected dose per gram of tissue (%ID/g) in the experiment with 123 I-MIBG, respectively. Prazosin, urapidil, and metoprolol were as effective as treatment with other adrenergic

Technetium-99m labeled 1-(4-fluorobenzyl)-4-(2-mercapto-2-methyl-4-azapentyl)-4- (2-mercapto-2-methylp ropylamino)-piperidine and iodine-123 metaiodobenzylguanidine for studying cardiac adrenergic function: a comparison of the uptake characteristics in vascular smooth muscle cells and neonatal cardiac myocytes, and an investigation in rats

Energy Technology Data Exchange (ETDEWEB)

Samnick, Samuel E-mail: rassam@uniklinik-saarland.de; Scheuer, Claudia; Muenks, Sven; El-Gibaly, Amr M.; Menger, Michael D.; Kirsch, Carl-Martin

2004-05-01

In developing technetium-99m-based radioligands for in vivo studies of cardiac adrenergic neurons, we compared the uptake characteristics of the {sup 99m}Tc-labeled 1-(4-fluorobenzyl)-4-(2-mercapto-2-methyl-4-azapentyl)-4- (2-mercapto-2-methylpropylamino)-piperidine ({sup 99m}Tc-FBPBAT) with those of the clinically established meta-[{sup 123}I]iodobenzylguanidine ({sup 123}I-MIBG) in rat vascular smooth muscle cells and neonatal cardiac myocytes. Furthermore, the cardiac and extracardiac uptake of both radiopharmaceuticals was assessed in intact rats and in rats pretreated with various {alpha}- and {beta}-adrenoceptor drugs, and adrenergic reuptake blocking agents. The uptake of {sup 99m}Tc-FBPBAT and {sup 123}I-MIBG into vascular smooth muscle cells and neonatal cardiac myocytes was rapid; more than 85% of the radioactivity accumulation into the cells occurring within the first 3 minutes. Radioactivity uptake after a 60-minute incubation at 37 degree sign C (pH 7.4) varied from 15% to 65% of the total loaded activity per million cells. In all cases, {sup 99m}Tc-FBPBAT showed the higher uptake, relative to {sup 123}I-MIBG, at any given cell concentration. The cellular uptake of {sup 99m}Tc-FBPBAT was lower at 4 degree sign C and 20 degree sign C than at 37 degree sign C. In contrast, the {sup 123}I-MIBG uptake was only slightly temperature dependent. Inhibition experiments confirmed that the cellular uptake of {sup 123}I-MIBG is mediated by the uptake-I carrier, whereas {alpha}{sub 1}- and {beta}{sub 1}-adrenoceptors were predominantly involved in the uptake of {sup 99m}Tc-FBPBAT into the cardiovascular tissues. Biodistribution studies in rats showed that {sup 99m}Tc-FBPBAT accumulated in myocardium after intravenous injection. Radioactivity in rat heart amounted to 2.32% and 1.91% of the injected dose per gram at 15 and 60 minutes postinjection, compared with 3.10% and 2.21% injected dose per gram of tissue (%ID/g) in the experiment with {sup 123}I

Liver, but not muscle, has an entrainable metabolic memory.

Directory of Open Access Journals (Sweden)

Sheng-Song Chen

Full Text Available Hyperglycemia in the hospitalized setting is common, especially in patients that receive nutritional support either continuously or intermittently. As the liver and muscle are the major sites of glucose disposal, we hypothesized their metabolic adaptations are sensitive to the pattern of nutrient delivery. Chronically catheterized, well-controlled depancreatized dogs were placed on one of three isocaloric diets: regular chow diet once daily (Chow or a simple nutrient diet (ND that was given either once daily (ND-4 or infused continuously (ND-C. Intraportal insulin was infused to maintain euglycemia. After 5 days net hepatic (NHGU and muscle (MGU glucose uptake and oxidation were assessed at euglycemia (120 mg/dl and hyperglycemia (200 mg/dl in the presence of basal insulin. While hyperglycemia increased both NHGU and MGU in Chow, NHGU was amplified in both groups receiving ND. The increase was associated with enhanced activation of glycogen synthase, glucose oxidation and suppression of pyruvate dehydrogenase kinase-4 (PDK-4. Accelerated glucose-dependent muscle glucose uptake was only evident with ND-C. This was associated with a decrease in PDK-4 expression and an increase in AMP-activated protein kinase (AMPK phosphorylation. Interestingly, ND-C markedly increased hepatic FGF-21 expression. Thus, augmentation of carbohydrate disposal in the liver, as opposed to the muscle, is not dependent on the pattern of nutrient delivery.

Muscle protein turnover in the elderly and its potential contribution to the development of sarcopenia.

Science.gov (United States)

Murton, Andrew J

2015-11-01

The underlying aetiology of sarcopenia appears multifaceted and not yet fully defined, but ultimately involves the gradual loss of muscle protein content over time. The present evidence suggests that the loss of lean tissue in the elderly is exacerbated by low dietary protein intake. Moreover, acute stable-isotope-based methodologies have demonstrated that the muscle anabolic response to a given amount of protein may decline with age, a phenomenon that has been termed anabolic resistance. Although the mechanism responsible for the inability of muscle to mount a satisfactory anabolic response to protein provision with increasing age is presently unknown, it does not appear due to impaired digestion or absorption of dietary protein. Rather, the issue could reside with any combination of: a diminished delivery of amino acids to peripheral tissues, impaired uptake of amino acids into muscle cells, or an inability of amino acids to elicit intracellular events pivotal for anabolism to occur. Despite the presence of anabolic resistance to dietary protein, present evidence suggests that protein supplementation may be able to overcome these issues, particularly when combined with resistance exercise programmes. As such, protein supplementation may prove to be an effective approach to delay the loss of muscle mass with age and has led to calls for the recommended daily intake of protein to be increased for the elderly population.

Effect of hypertensive rat plasma on ion transport of cultured vascular smooth muscle

International Nuclear Information System (INIS)

Magargal, W.W.; Overbeck, H.W.

1986-01-01

We layered fresh, unprocessed plasma from healthy rats with early (less than or equal to 7 days) or benign, chronic (greater than 3 wk) one-kidney, one-clip hypertension and from paired one-kidney normotensive control rats over confluent primary-cultured rat aortic smooth muscle cells. Plasma from all rats increased cellular ouabain-sensitive 86 Rb + uptake and sodium content and decreased ouabain-insensitive 86 Rb + uptake compared with uptakes and content in the presence of balanced salt solution (P less than 0.01). Cells incubated in the presence of plasma from rats with early (P less than 0.02) or chronic hypertension (P less than 0.01) had significantly reduced ouabain-sensitive 86 Rb + uptake when compared with cells incubated in normotensive plasma, but their intracellular Na+ contents were not lower. We no longer detected this uptake difference when chronic hypertensives drank 0.9% NaCl instead of water. Plasma from hypertensive rats also altered ouabain-insensitive 86 Rb + uptake by the cultured cells. These findings of this new, reproducible, and specific assay system support the hypothesis that plasma factors inhibit the membrane sodium-potassium pump in vascular smooth muscle cells in this form of hypertension. The abnormality occurs in both early and chronic stages, but may not be related to sodium intake. The data also provide evidence for plasma factors in hypertension altering membrane K+ permeability

Mechanisms limiting glycogen storage in muscle during prolonged insulin stimulation

DEFF Research Database (Denmark)

Richter, Erik; Hansen, S A; Hansen, B F

1988-01-01

increased muscle glycogen concentrations to maximal values 2, 3, and 3.5 times above normal fed levels in fast-twitch white, slow-twitch red, and fast-twitch red fibers, respectively. Glucose uptake decreased (mean +/- SE) from 34.9 +/- 1.2 mumol.g-1.h-1 at 0 h to 7.5 +/- 0.7 after 7 h of perfusion. During...... compared with initial values. Total muscle water concentration decreased during glycogen loading of the muscles. Mechanisms limiting glycogen storage under maximal insulin stimulation include impaired insulin-stimulated membrane transport of glucose as well as impaired intracellular glucose disposal....

Direct observation of glycogen synthesis in human muscle with 13C NMR

International Nuclear Information System (INIS)

Jue, T.; Rothman, D.L.; Shulman, G.I.; Tavitian, B.A.; DeFronzo, R.A.; Shulman, R.G.

1989-01-01

On the basis of previous indirect measurements, skeletal muscle has been implicated as the major site of glucose uptake and it has been suggested that muscle glycogen formation is the dominant pathway. However, direct measurements of the rates of glycogen synthesis have not been possible by previous techniques. The authors have developed 13 C NMR methods to measure directly the rate of human muscle glycogen formation from infused, isotopically labeled [1- 13 C]glucose. They show that under conditions of imposed hyperglycemia and hyperinsulinemia, a majority of the infused glucose was converted to muscle glycogen in a normal man. This directly shows that muscle is the major site of glucose disposal under these conditions, and provides quantitation of the glucose flux to muscle glycogen

Adenosine formation in contracting primary rat skeletal muscle cells and endothelial cells in culture

DEFF Research Database (Denmark)

Hellsten, Ylva; Frandsen, Ulrik

1997-01-01

1. The present study examined the capacity for adenosine formation, uptake and metabolism in contracting primary rat muscle cells and in microvascular endothelial cells in culture. 2. Strong and moderate electrical simulation of skeletal muscle cells led to a significantly greater increase....... 3. Addition of microvascular endothelial cells to the cultured skeletal muscle cells enhanced the contraction-induced accumulation of extracellular adenosine (P Skeletal muscle cells were...... in the extracellular adenosine concentration (421 +/- 91 and 235 +/- 30 nmol (g protein)-1, respectively; P muscle cells (161 +/- 20 nmol (g protein)-1). The ATP concentration was lower (18%; P contracted, but not in the moderately contracted muscle cells...

18F FDG Uptake of Human Testis on PET/CT: Correlation with Age, Sex Hormones, and Vasectomy

International Nuclear Information System (INIS)

Moon, Seung Hwan; Eo, Jae Sun; Lee, Jong Jin; Chung, June Key; Lee, Dong Soo; Lee, Myung Chul

2011-01-01

The purpose of this study was to evaluate glucose metabolism of normal human testis on 18F FDG PET/CT and to assess possible correlation among age, the serum levels of sex hormones, and vasectomy. 18F FDG PET/CT was performed in 66 normal healthy men (50.8±13.6 years, range 22-81), and mean standard uptake values (SUV) of 18F FDG in testis and adductor muscle were measured. Testis muscle SUV ratios (T/M ratios) were calculated. Serum levels of total testosterone, free testosterone, estradiol, and of sex hormone binding globulin (SHBG) were measured. We searched for correlations between T/M ratios and age and the serum concentrations of sex hormones. 18F FDG PET/CT was also performed in 32 vasectomized men (55.7±7.8 years, range 38-71) and 52 nonvasectomized men (55.4±11.6 years, range 37-72). Mean SUVs of testis and adductor muscle were measured, and T/M ratios were calculated. A significant age related decline was found in T/M ratio (r=-0.509, p 18F FDG uptake may have attributed to testicular function and testicular histology. Our findings may have important implications for the interpretation of testicular 18F FDG uptake in the normal adult population.

Muscle involvement in leprosy: study of the anterior tibial muscle in 40 patients Alterações musculares na lepra: estudo do músculo tibial anterior em 40 pacientes

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LINEU CESAR WERNECK

1999-09-01

Full Text Available The involvement of skeletal striated muscle in leprosy is considered secondary due to peripheral neuropathy, but some studies point it to a primary muscle lesion. In order to investigate the muscle involvement in leprosy, we studied 40 patients (lepromatous 23, tuberculoid 13, borderline 2 and indeterminate 2. The motor nerve conduction of the peroneal nerves had a reduction of the velocity, decreased compound muscle action potential and sometimes absence of potentials. The electromyographic study of the anterior tibial muscle showed signs of recent and chronic denervation in 77.5% of the cases and no myopathic potentials. The anterior tibial muscle biopsy revealed denervation in 45% of the cases, interstitial inflammatory myopathy in 30% and mixed (myopathic and neuropathic pattern in 12.5%. Acid fast bacillus was detected in 25% of the cases, always in the interstitial tissue. Inflammatory reaction was present in the interstitial space and in patients with the lepromatous type. The histological findings clearly defined the presence of the so-called "Leprous Interstitial Myositis" on the top of denervation signs.O envolvimento do músculo estriado na lepra é considerado secundário à lesão dos nervos periféricos, mas alguns estudos relataram acometimento muscular primário. A fim de verificar esta controvérsia estudamos 40 pacientes com lepra, sendo 23 da forma lepromatosa, 13 da tuberculoide, 2 borderline e 2 indeterminada. Realizamos a neurocondução do nervo peroneiro, junto com eletromiografia e biópsia do músculo tibial anterior. Encontramos redução de velocidade de condução, da amplitude e algumas vezes ausência de potenciais no nervo peroneiro. A eletromiografia do tibial anterior mostrou sinais de desinervação recente e crônica em 77,5% dos casos e não foi encontrada evidência de padrão "miopático". A biópsia do músculo tibial anterior revelou desinervação em 45% dos casos, miopatia inflamatória intersticial em

Phytanic acid stimulates glucose uptake in a model of skeletal muscles, the primary porcine myotubes

DEFF Research Database (Denmark)

Che, Brita Ngum; Oksbjerg, Niels; Hellgren, Lars

2013-01-01

and tritiated 2-deoxyglucose (2-DOG) was used to measure glucose uptake, in relation to PA and 2-DOG exposure times and also in relation to PA and insulin concentrations. The MIXED procedure model of SAS was used for statistical analysis of data. RESULTS: PA increased glucose uptake by approximately 35...

Running Economy from a Muscle Energetics Perspective

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Jared R. Fletcher

2017-06-01

Full Text Available The economy of running has traditionally been quantified from the mass-specific oxygen uptake; however, because fuel substrate usage varies with exercise intensity, it is more accurate to express running economy in units of metabolic energy. Fundamentally, the understanding of the major factors that influence the energy cost of running (Erun can be obtained with this approach. Erun is determined by the energy needed for skeletal muscle contraction. Here, we approach the study of Erun from that perspective. The amount of energy needed for skeletal muscle contraction is dependent on the force, duration, shortening, shortening velocity, and length of the muscle. These factors therefore dictate the energy cost of running. It is understood that some determinants of the energy cost of running are not trainable: environmental factors, surface characteristics, and certain anthropometric features. Other factors affecting Erun are altered by training: other anthropometric features, muscle and tendon properties, and running mechanics. Here, the key features that dictate the energy cost during distance running are reviewed in the context of skeletal muscle energetics.

Enhanced muscle glucose metabolism after exercise

DEFF Research Database (Denmark)

Richter, Erik; Garetto, L P; Goodman, M N

1984-01-01

Studies in the rat suggest that after voluntary exercise there are two phases of glycogen repletion in skeletal muscle (preceding study). In phase I glucose utilization and glycogen synthesis are enhanced both in the presence and absence of insulin, whereas in phase II only the increase in the pr......Studies in the rat suggest that after voluntary exercise there are two phases of glycogen repletion in skeletal muscle (preceding study). In phase I glucose utilization and glycogen synthesis are enhanced both in the presence and absence of insulin, whereas in phase II only the increase...... in the stimulated leg closely mimicked that observed previously after voluntary exercise on a treadmill. With no insulin added to the perfusate, glucose incorporation into glycogen was markedly enhanced in muscles that were glycogen depleted as were the uptake of 2-deoxyglucose and 3-O-methylglucose. Likewise......, the stimulation of these processes by insulin was enhanced and continued to be so 2 h later when the muscles of the stimulated leg had substantially repleted their glycogen stores. The results suggest that the increases in insulin-mediated glucose utilization and glycogen synthesis in muscle after exercise...

Effect of exercise on insulin action in human skeletal muscle

DEFF Research Database (Denmark)

Richter, Erik; Mikines, K J; Galbo, Henrik

1989-01-01

The effect of 1 h of dynamic one-legged exercise on insulin action in human muscle was studied in 6 healthy young men. Four hours after one-legged knee extensions, a three-step sequential euglycemic hyperinsulinemic clamp combined with arterial and bilateral femoral vein catheterization...... was performed. Increased insulin action on glucose uptake was found in the exercised compared with the rested thigh at mean plasma insulin concentrations of 23, 40, and 410 microU/ml. Furthermore, prior contractions directed glucose uptake toward glycogen synthesis and increased insulin effects on thigh O2...... consumption and at some insulin concentrations on potassium exchange. In contrast, no change in insulin effects on limb exchange of free fatty acids, glycerol, alanine or tyrosine were found after exercise. Glycogen concentration in rested vastus lateralis muscle did not increase measurably during the clamp...

Glucagon like peptide-1-induced glucose metabolism in differentiated human muscle satellite cells is attenuated by hyperglycemia

DEFF Research Database (Denmark)

Green, Charlotte J; Henriksen, Tora I; Pedersen, Bente K

2012-01-01

Glucagon like peptide-1 (GLP-1) stimulates insulin secretion from the pancreas but also has extra-pancreatic effects. GLP-1 may stimulate glucose uptake in cultured muscle cells but the mechanism is not clearly defined. Furthermore, while the pancreatic effects of GLP-1 are glucose-dependent, the......Glucagon like peptide-1 (GLP-1) stimulates insulin secretion from the pancreas but also has extra-pancreatic effects. GLP-1 may stimulate glucose uptake in cultured muscle cells but the mechanism is not clearly defined. Furthermore, while the pancreatic effects of GLP-1 are glucose...

Age-related differences in skeletal muscle microvascular response to exercise as detected by contrast-enhanced ultrasound (CEUS).

Science.gov (United States)

Hildebrandt, Wulf; Schwarzbach, Hans; Pardun, Anita; Hannemann, Lena; Bogs, Björn; König, Alexander M; Mahnken, Andreas H; Hildebrandt, Olaf; Koehler, Ulrich; Kinscherf, Ralf

2017-01-01

Aging involves reductions in exercise total limb blood flow and exercise capacity. We hypothesized that this may involve early age-related impairments of skeletal muscle microvascular responsiveness as previously reported for insulin but not for exercise stimuli in humans. Using an isometric exercise model, we studied the effect of age on contrast-enhanced ultrasound (CEUS) parameters, i.e. microvascular blood volume (MBV), flow velocity (MFV) and blood flow (MBF) calculated from replenishment of Sonovue contrast-agent microbubbles after their destruction. CEUS was applied to the vastus lateralis (VLat) and intermedius (VInt) muscle in 15 middle-aged (MA, 43.6±1.5 years) and 11 young (YG, 24.1±0.6 years) healthy males before, during, and after 2 min of isometric knee extension at 15% of peak torque (PT). In addition, total leg blood flow as recorded by femoral artery Doppler-flow. Moreover, fiber-type-specific and overall capillarisation as well as fiber composition were additionally assessed in Vlat biopsies obtained from CEUS site. MA and YG had similar quadriceps muscle MRT-volume or PT and maximal oxygen uptake as well as a normal cardiovascular risk factors and intima-media-thickness. During isometric exercise MA compared to YG reached significantly lower levels in MFV (0.123±0.016 vs. 0.208±0.036 a.u.) and MBF (0.007±0.001 vs. 0.012±0.002 a.u.). In the VInt the (post-occlusive hyperemia) post-exercise peaks in MBV and MBF were significantly lower in MA vs. YG. Capillary density, capillary fiber contacts and femoral artery Doppler were similar between MA and YG. In the absence of significant age-related reductions in capillarisation, total leg blood flow or muscle mass, healthy middle-aged males reveal impaired skeletal muscle microcirculatory responses to isometric exercise. Whether this limits isometric muscle performance remains to be assessed.

Effects of thyroid hormones on calcium contents and 45Ca exchange in rat skeletal muscle

International Nuclear Information System (INIS)

Everts, M.E.; Clausen, T.

1986-01-01

In 4-wk-old rats, pretreatment with L-triiodothyronine (T3) increased calcium content by 100% and the 30-min 45 Ca uptake by 64% in the soleus, whereas the extensor digitorum longus (EDL) muscle showed no significant change. The stimulation of 45 Ca uptake was resistant to dantrolene and methoxyverapamil (D600) and could not be attributed to altered permeability of the plasma membrane to calcium, but appears to reflect increased net accumulation of calcium in intracellular pools. The stimulating effect of high K0 (20 mM) on 45 Ca uptake was more pronounced in soleus than in EDL and could be suppressed by dantrolene and D600. The results indicate that the effects of T3 on calcium content and 45 Ca exchange are primarily exerted on muscles containing a large proportion of slow-twitch, oxidative fibers. In soleus muscle from hyperthyroid rats the stimulating effects of high K0 on 45 Ca uptake and lactate production were, respectively, 3.4 and 4.5 times larger than in those obtained from controls. These observations further support the earlier proposed idea [C. van Hardeveld and T. Clausen. Am. J. Physiol. 247 (Endocrinol. Metab. 10): E421-E430, 1984] that the metabolic effects of thyroid hormone depend on the availability of cellular as well as extracellular calcium

Effects of thyroid hormones on calcium contents and 45Ca exchange in rat skeletal muscle

Energy Technology Data Exchange (ETDEWEB)

Everts, M.E.; Clausen, T.

1986-09-01

In 4-wk-old rats, pretreatment with L-triiodothyronine (T3) increased calcium content by 100% and the 30-min /sup 45/Ca uptake by 64% in the soleus, whereas the extensor digitorum longus (EDL) muscle showed no significant change. The stimulation of /sup 45/Ca uptake was resistant to dantrolene and methoxyverapamil (D600) and could not be attributed to altered permeability of the plasma membrane to calcium, but appears to reflect increased net accumulation of calcium in intracellular pools. The stimulating effect of high K0 (20 mM) on /sup 45/Ca uptake was more pronounced in soleus than in EDL and could be suppressed by dantrolene and D600. The results indicate that the effects of T3 on calcium content and /sup 45/Ca exchange are primarily exerted on muscles containing a large proportion of slow-twitch, oxidative fibers. In soleus muscle from hyperthyroid rats the stimulating effects of high K0 on /sup 45/Ca uptake and lactate production were, respectively, 3.4 and 4.5 times larger than in those obtained from controls. These observations further support the earlier proposed idea (C. van Hardeveld and T. Clausen. Am. J. Physiol. 247 (Endocrinol. Metab. 10): E421-E430, 1984) that the metabolic effects of thyroid hormone depend on the availability of cellular as well as extracellular calcium.

Verapamil reverses PTH- or CRF-induced abnormal fatty acid oxidation in muscle

International Nuclear Information System (INIS)

Perna, A.F.; Smogorzewski, M.; Massry, S.G.

1988-01-01

Chronic renal failure (CRF) is associated with impaired long chain fatty acids (LCFA) oxidation by skeletal muscle mitochondria. This is due to reduced activity of carnitine palmitoyl transferase (CPT). These derangements were attributed to the secondary hyperparathyroidism of CRF, since prior parathyroidectomy in CRF rats reversed these abnormalities and PTH administration to normal rats reproduced them. It was proposed that these effects of PTH are mediated by its ionophoric property leading to increased entry of calcium into skeletal muscle. A calcium channel blocker may, therefore, correct these derangements. The present study examined the effects of verapamil on LCFA oxidation, CPT activity by skeletal muscle mitochondria, and 45 Ca uptake by skeletal muscle obtained from CRF rats and normal animals treated with PTH with and without verapamil. Both four days of PTH administration and 21 days of CRF produced significant (P less than 0.01) reduction in LCFA oxidation and CPT activity of skeletal muscle mitochondria, and significant (P less than 0.01) increment in 45 Ca uptake by skeletal muscle. Simultaneous treatment with verapamil corrected all these derangements. Administration of verapamil alone to normal rats did not cause a significant change in any of these parameters. The data are consistent with the proposition that the alterations in LCFA in CRF or after PTH treatment are related to the ionophoric action of the hormone and could be reversed by a calcium channel blocker

Scintigraphic evaluation of muscle damage following extreme exercise: concise communication

International Nuclear Information System (INIS)

Matin, P.; Lang, G.; Carretta, R.; Simon, G.

1983-01-01

Total body Tc-99m pyrophosphate scintigraphy was performed on 11 ''ultramarathon'' runners to assess the ability of nuclear medicine techniques to evaluate skeletal-muscle injury due to exercise. We found increased muscle radionuclide concentration in 90% of the runners. The pattern of muscle uptake correlated with the regions of maximum pain. The detection of exercise-induced rhabdomyolysis appeared to be best when scintigraphy was performed within 48 hr after the race, and to be almost undetectable after about a week. It was possible to differentiate muscle injury from joint and osseous abnormalities such as bone infarct or stress fracture. Although 77% of the runners had elevated serum creatine kinase MB activity, cardiac scintigraphy showed no evidence of myocardial injury

A Study on Clinical Activity of Myositis by the Use of Radioisotope Bone Scan in the Patients with Dermatomyositis - polymyositis

International Nuclear Information System (INIS)

Choi, Sung Jae; Koh, Chang Soon

1982-01-01

To evaluate the diagnostic usefulness of radioisotope bone scan and clinical activity of myositis, bone scan using 99m Tc-Methylene diphosphonate was serially done before and after treatment with prednisolone in 10 patients with well- documented dermatomyositis-polymyositis. The observed results were as follows. 1. In all 10 patients before treatment with prednisolone, the bone scans showed evidence of increased muscle uptake. Muscle uptake was markedly increased in 4 patients, moderately increased in 3 patients and minimally increased in 3 patients. 2. The site of increased muscle uptake was consistent with the site of clinically involved muscle which was weak and tender. 3. The degree of muscle uptake correlated with the severity of the muscle weakness and tenderness at the scan was done. In all 10 patients treated with high dose prednisolone, muscle uptake was decreased following therapy. Above results suggest the radioisotope bone scanning may be useful in the diagnosis and treatment of patient with dermatomyositis-polymyositis.

The muscle protein synthetic response to food ingestion.

Science.gov (United States)

Gorissen, Stefan H M; Rémond, Didier; van Loon, Luc J C

2015-11-01

Preservation of skeletal muscle mass is of great importance for maintaining both metabolic health and functional capacity. Muscle mass maintenance is regulated by the balance between muscle protein breakdown and synthesis rates. Both muscle protein breakdown and synthesis rates have been shown to be highly responsive to physical activity and food intake. Food intake, and protein ingestion in particular, directly stimulates muscle protein synthesis rates. The postprandial muscle protein synthetic response to feeding is regulated on a number of levels, including dietary protein digestion and amino acid absorption, splanchnic amino acid retention, postprandial insulin release, skeletal muscle tissue perfusion, amino acid uptake by muscle, and intramyocellular signaling. The postprandial muscle protein synthetic response to feeding is blunted in many conditions characterized by skeletal muscle loss, such as aging and muscle disuse. Therefore, it is important to define food characteristics that modulate postprandial muscle protein synthesis. Previous work has shown that the muscle protein synthetic response to feeding can be modulated by changing the amount of protein ingested, the source of dietary protein, as well as the timing of protein consumption. Most of this work has studied the postprandial response to the ingestion of isolated protein sources. Only few studies have investigated the postprandial muscle protein synthetic response to the ingestion of protein dense foods, such as dairy and meat. The current review will focus on the capacity of proteins and protein dense food products to stimulate postprandial muscle protein synthesis and identifies food characteristics that may modulate the anabolic properties. Copyright © 2015 Elsevier Ltd. All rights reserved.

AMPK-α2 is involved in exercise training-induced adaptations in insulin-stimulated metabolism in skeletal muscle following high-fat diet.

Science.gov (United States)

Abbott, Marcia J; Turcotte, Lorraine P

2014-10-15

AMP-activated protein kinase (AMPK) has been studied extensively and postulated to be a target for the treatment and/or prevention of metabolic disorders such as insulin resistance. Exercise training has been deemed a beneficial treatment for obesity and insulin resistance. Furthermore, exercise is a feasible method to combat high-fat diet (HFD)-induced alterations in insulin sensitivity. The purpose of this study was to determine whether AMPK-α2 activity is required to gain beneficial effects of exercise training with high-fat feeding. Wild-type (WT) and AMPK-α2 dominant-negative (DN) male mice were fed standard diet (SD), underwent voluntary wheel running (TR), fed HFD, or trained with HFD (TR + HFD). By week 6, TR, irrespective of genotype, decreased blood glucose and increased citrate synthase activity in both diet groups and decreased insulin levels in HFD groups. Hindlimb perfusions were performed, and, in WT mice with SD, TR increased insulin-mediated palmitate uptake (76.7%) and oxidation (>2-fold). These training-induced changes were not observed in the DN mice. With HFD, TR decreased palmitate oxidation (61-64%) in both WT and DN and increased palmitate uptake (112%) in the WT with no effects on palmitate uptake in the DN. With SD, TR increased ERK1/2 and JNK1/2 phosphorylation, regardless of genotype. With HFD, TR reduced JNK1/2 phosphorylation, regardless of genotype, carnitine palmitoyltransferase 1 expression in WT, and CD36 expression in both DN and WT. These data suggest that low AMPK-α2 signaling disrupts, in part, the exercise training-induced adaptations in insulin-stimulated metabolism in skeletal muscle following HFD. Copyright © 2014 the American Physiological Society.

Calf muscle involvement in Becker muscular dystrophy: when size does not matter.

Science.gov (United States)

Monforte, Mauro; Mercuri, Eugenio; Laschena, Francesco; Ricci, Enzo; Tasca, Giorgio

2014-12-15

Calf hypertrophy is a common feature in Becker muscular dystrophy (BMD), and it is still debated to which extent fatty degeneration or true muscle hypertrophy account for it. We wanted to investigate the relative contribution of these two components using a simple image analysis approach and their possible correlation with disease severity. Twenty-nine BMD patients' MRI scans were analyzed. A semiquantitative visual score assessing fatty replacement of calf muscles (calf MRI score, CMS) was calculated and correlated with the cross sectional area (CSA) of lower leg posterior compartment muscles, digitally measured on acquired images. The correlation between CSA and CMS was not significant. CMS in contrast correlated with disease severity (p<0.001) while CSA did not (p=0.969). In BMD, a major contribution to calf hypertrophy is provided by real muscle hypertrophy rather than by fatty degeneration. CMS appears to be a potential surrogate marker of disease severity. Copyright © 2014 Elsevier B.V. All rights reserved.

Differential metabolic effects of casein and soy protein meals on skeletal muscle in healthy volunteers.

Science.gov (United States)

Luiking, Yvette C; Engelen, Mariëlle P K J; Soeters, Peter B; Boirie, Yves; Deutz, Nicolaas E P

2011-02-01

Dietary protein intake is known to affect whole body and interorgan protein turnover. We examined if moderate-nitrogen and carbohydrate casein and soy meals have a different effect on skeletal muscle protein and amino acid kinetics in healthy young subjects. Muscle protein and amino acid kinetics were measured in the postabsorptive state and during 4-h enteral intake of isonitrogenous [0.21 g protein/(kg body weight. 4 h)] protein-based test meals, which contained either casein (CAPM; n = 12) or soy protein (SOPM; n = 10) in 2 separate groups. Stable isotope and muscle biopsy techniques were used to study metabolic effects. The net uptake of glutamate, serine, histidine, and lysine across the leg was larger during CAPM than during SOPM intake. Muscle concentrations of glutamate, serine, histidine, glutamine, isoleucine and BCAA changed differently after CAPM and SOPM (P CAPM and SOPM, but differences in their (net) breakdown rates were not significant. Muscle protein synthesis was not different between CAPM and SOPM. Moderate-nitrogen casein and soy protein meals differently alter leg amino acid uptake without a significant difference in influencing acute muscle protein metabolism. Copyright © 2010 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Case of sarcoidosis with generalized increased uptake of /sup 67/Ga-citrate

Energy Technology Data Exchange (ETDEWEB)

Okada, Yoshitaka; Ohtake, Tohru; Nishikawa, Junichi; Iio, Masahiro; Machida, Kikuo

1985-10-01

A case of sarcoidosis was reported in which gallium-67 scintigraphy showed increased uptake in generalized sarcoid lesions. Gallium-67 uptake in skin lesions was also seen, which is rare in literature. A 22-year-old male patient was admitted to our hospital. The patient had a history of general fatigue, polydipsia and polyuria. On physical examination, swelling of the bilateral parotid glands and lacrimal glands was noted. There were many subcutaneous nodules, especially in both arms. Superficial lymphademopathy was also noted in cervical and inguinal regions. He complained of bilateral amblyopia, and gonioscopy revelaed some nodules of the uvea. Coexistent diabetes insipidus was diagnosed with dehydration test. Chest roentgenogram showed bilateral hilar lymphadenopathy. Gallium-67 scintigram showed increased uptake in bilateral parotid glands and lacrimal glands. There were multiple abnormal uptakes in the neck, mediastinum and the inguinal region. Abnormal uptake was also noted in the subcutaneous nodules. Biopsy was performed from the lesions in the parotid glands, cervical lymph nodes, subcutaneous nodules and triceps muscles. Diagnosis of sarcoidosis was confirmed histopathologically. (J.P.N.).

A case of sarcoidosis with generalized increased uptake of 67Ga-citrate

International Nuclear Information System (INIS)

Okada, Yoshitaka; Ohtake, Tohru; Nishikawa, Junichi; Iio, Masahiro; Machida, Kikuo.

1985-01-01

A case of sarcoidosis was reported in which gallium-67 scintigraphy showed increased uptake in generalized sarcoid lesions. Gallium-67 uptake in skin lesions was also seen, which is rare in literature. A 22-year-old male patient was admitted to our hospital. The patient had a history of general fatigue, polydipsia and polyuria. On physical examination, swelling of the bilateral parotid glands and lacrimal glands was noted. There were many subcutaneous nodules, especially in both arms. Superficial lymphademopathy was also noted in cervical and inguinal regions. He complained of bilateral amblyopia, and gonioscopy revelaed some nodules of the uvea. Coexistent diabetes insipidus was diagnosed with dehydration test. Chest roentgenogram showed bilateral hilar lymphadenopathy. Gallium-67 scintigram showed increased uptake in bilateral parotid glands and lacrimal glands. There were multiple abnormal uptakes in the neck, mediastinum and the inguinal region. Abnormal uptake was also noted in the subcutaneous nodules. Biopsy was performed from the lesions in the parotid glands, cervical lymph nodes, subcutaneous nodules and triceps muscles. Diagnosis of sarcoidosis was confirmed histopathologically. (J.P.N.)

Evaluation of muscle MRI in amyotrophic lateral sclerosis

International Nuclear Information System (INIS)

Baba, Yuri; Kuroiwa, Yoshiyuki

2005-01-01

Various objective measurements can be used to diagnose amyotrophic lateral sclerosis (ALS). T2-weighted brain MRI images revealed high signal areas at the posterior limb of the internal capsules in ALS patients. Recently, muscle MRI proved useful to evaluate abnormalities of the muscle in myositis patients. Therefore, in the present study, we examined muscle MRI of leg muscles in ALS patients, and correlated MRI with functional measurements, such as muscle strength, and compound muscle action potential amplitude of the tibialis anterior (TA) after stimulation of the peroneal nerve. The subjects consisted of 10 ALS patients (7 males and 3 females), ranging in age from 49 to 87. Neurologic symptoms at the onset of ALS consisted of bulbar dysfunction in one patient, upper extremity involvement in three patients, and lower extremity involvement in six patients. Muscle MRI of the legs was performed in 9 (ALS patients. A peripheral nerve conduction study was performed on the peroneal nerve, with the recording electrode over the TA. The T2-weighted muscle MRI images revealed high signal aeras in the muscle in six ALS patients, whose muscle weakness existed predominantly in the lower extremities. Extracellular fluid accumulation has been proposed to be responsible for the signal increase of denervated muscles on T2-weighted muscle MRI images. We assume that muscle MRI is useful to demonstrate the distribution of muscle involvement in ALS patients and to assess the disease's stage. (author)

Is Walking Capacity in Subjects with Multiple Sclerosis Primarily Related to Muscle Oxidative Capacity or Maximal Muscle Strength? A Pilot Study

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Dominique Hansen

2014-01-01

Full Text Available Background and Purpose. Walking capacity is reduced in subjects with multiple sclerosis (MS. To develop effective exercise interventions to enhance walking capacity, it is important to determine the impact of factors, modifiable by exercise intervention (maximal muscle strength versus muscle oxidative capacity, on walking capacity. The purpose of this pilot study is to discriminate between the impact of maximal muscle strength versus muscle oxidative capacity on walking capacity in subjects with MS. Methods. From 24 patients with MS, muscle oxidative capacity was determined by calculation of exercise-onset oxygen uptake kinetics (mean response time during submaximal exercise bouts. Maximal muscle strength (isometric knee extension and flexion peak torque was assessed on dynamometer. All subjects completed a 6-minute walking test. Relationships between walking capacity (as a percentage of normal value and muscle strength (of knee flexors and extensors versus muscle oxidative capacity were assessed in multivariate regression analyses. Results. The expanded disability status score (EDSS showed a significant univariate correlation (r=-0.70, P<0.004 with walking capacity. In multivariate regression analyses, EDSS and mean response time, but not muscle strength, were independently related to walking capacity (P<0.05. Conclusions. Walking distance is, next to disability level and not taking neurologic symptoms/deficits into account, primarily related to muscle oxidative capacity in subjects with MS. Additional study is needed to further examine/verify these findings.

Overexpression of PGC-1α Increases Fatty Acid Oxidative Capacity of Human Skeletal Muscle Cells

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Nataša Nikolić

2012-01-01

Full Text Available We investigated the effects of PGC-1α (peroxisome proliferator-activated receptor γ coactivator-1α overexpression on the oxidative capacity of human skeletal muscle cells ex vivo. PGC-1α overexpression increased the oxidation rate of palmitic acid and mRNA expression of genes regulating lipid metabolism, mitochondrial biogenesis, and function in human myotubes. Basal and insulin-stimulated deoxyglucose uptake were decreased, possibly due to upregulation of PDK4 mRNA. Expression of fast fiber-type gene marker (MHCIIa was decreased. Compared to skeletal muscle in vivo, PGC-1α overexpression increased expression of several genes, which were downregulated during the process of cell isolation and culturing. In conclusion, PGC-1α overexpression increased oxidative capacity of cultured myotubes by improving lipid metabolism, increasing expression of genes involved in regulation of mitochondrial function and biogenesis, and decreasing expression of MHCIIa. These results suggest that therapies aimed at increasing PGC-1α expression may have utility in treatment of obesity and obesity-related diseases.

Role of cyclic GMP in cells with the properties of smooth muscle cultured from the rat myometrium

International Nuclear Information System (INIS)

Krall, J.F.; Morin, A.

1986-01-01

Cells growing in culture with previously described properties of rat uterine smooth muscle accumulated 45 Ca 2+ from the medium. Ca 2+ uptake by these cells was stimulated by the addition to the medium of 8-bromo-cGMP but not by 8-bromo-cAMP. Ca 2+ uptake was also stimulated by carbachol and by the nitro-vasodilator nitroprusside. Although cholinergic agonists have been shown previously to stimulate contraction but not cGMP synthesis in the rat myometrium, both carbachol and nitroprusside stimulated cGMP production by the cultured cells. These results suggested the cells had cholinergic receptor-medicated functions that reflected some neurotransmitter-sensitive properties of uterine smooth muscle in situ. When determined by a specific radioligand binding assay, subcellular fractions of the cultured cells bound muscarinic cholinergic agonists and antagonists with affinities expected of the muscarinic receptor. The cells were also sensitive to the β-adrenergic catecholamine agonist isoproterenol, which stimulated cAMP production but not Ca 2+ uptake. Carbachol failed to inhibit isoproterenol-dependent cAMP production, which is an important property of the cholinergic receptor in uterine smooth muscle in situ. These results suggest some but not all acetylcholine-sensitive properties of uterine smooth muscle may be retained in cell culture

A small-molecule benzimidazole derivative that potently activates AMPK to increase glucose transport in skeletal muscle: comparison with effects of contraction and other AMPK activators.

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Lai, Yu-Chiang; Kviklyte, Samanta; Vertommen, Didier; Lantier, Louise; Foretz, Marc; Viollet, Benoît; Hallén, Stefan; Rider, Mark H

2014-06-15

AMPK (AMP-activated protein kinase) is an attractive therapeutic drug target for treating metabolic disorders. We studied the effects of an AMPK activator developed by Merck (ex229 from patent application WO2010036613), comparing chemical activation with contraction in intact incubated skeletal muscles. We also compared effects of ex229 with those of the Abbott A769662 compound and AICAR (5-amino-4-imidazolecarboxamide riboside). In rat epitrochlearis muscle, ex229 dose-dependently increased AMPK activity of α1-, α2-, β1- and β2-containing complexes with significant increases in AMPK activity seen at a concentration of 50 μM. At a concentration of 100 μM, AMPK activation was similar to that observed after contraction and importantly led to an ~2-fold increase in glucose uptake. In AMPK α1-/α2-catalytic subunit double-knockout myotubes incubated with ex229, the increases in glucose uptake and ACC (acetyl-CoA carboxylase) phosphorylation seen in control cells were completely abolished, suggesting that the effects of the compound were AMPK-dependent. When muscle glycogen levels were reduced by ~50% after starvation, ex229-induced AMPK activation and glucose uptake were amplified in a wortmannin-independent manner. In L6 myotubes incubated with ex229, fatty acid oxidation was increased. Furthermore, in mouse EDL (extensor digitorum longus) and soleus muscles, ex229 increased both AMPK activity and glucose uptake at least 2-fold. In summary, ex229 efficiently activated skeletal muscle AMPK and elicited metabolic effects in muscle appropriate for treating Type 2 diabetes by stimulating glucose uptake and increasing fatty acid oxidation.

FDG uptake in the fatty tissues of supraclavicular and the vascular structure of the lung hilum

International Nuclear Information System (INIS)

Dang Yaping; Liu Gang; Li Miao

2004-01-01

Full text: Supraclavicular region (SR) and lung hilum (LH) are common sites for lymph node metastases. A commonly reported site of non-malignant FDG uptake on PET imaging in the SR is muscular uptake. PET/CT offers a unique technique to correlate PET findings with CT anatomy in the SR and LH. We carried out this study to investigate FDG uptake in SR and LH to find out the exact tissues of FDG uptake. From September 2002 to March 2003, 147 consecutive patients imaged by FDG PET/CT whole-body scan (GE Discovery LS, CT attenuation correction, OSEM reconstruction) were retrospectively reviewed. The presence of abnormal FDG uptake on PET images in SR and LH regions was evaluated and the corresponding CT findings on the same regions were also assessed. Of the 147 patients, 8 cases (2M, 6F and mean age 44 years) were found with increased symmetrical FDG uptake in the regions of the lower neck and shoulder as well as costo-vertebral articulations. The positive rates were 2.1% and 11.3% for men and women respectively, and the average rate was 5.4%. However, no FDG uptake was seen in the greater muscular structures of the cervical or thoracic spine. FDG uptake was seen in the fatty tissue between the shoulder muscle and the dorsal thoracic wall, but not within the muscles itself. Five patients (3M, 2F, age 56-74 years, 3.4%) showed abnormal FDG uptake in LH, which were definitely localized in the vascular structure of the lung hilum by CT. Co-registered PET/CT imaging shows that the FDG uptake, though well known in the SR and LH regions, is not fully located in greater muscular structures and lymph nodes, but in the costo-vertebral articulation complex of the thoracic spine and fatty tissue of the shoulders as well as in the vascular structure of both lung hilum. The FDG uptake in the fatty tissue of the shoulders was mostly seen in women, while the uptake in vascular structure of the lung hilum were found in aged people. (author)

FDG uptake in the fatty tissues of supraclavicular and the vascular structure of the lung hilum

International Nuclear Information System (INIS)

Dang Yaping; Liu Gang; Li Miao

2004-01-01

Objectives: To investigate FDG uptake on the sites of supraclavicular region (SR) and the lung hilum (LH) and find out the exact tissues of the uptake. Methods: Supraclavicular region (SR) and lung hilum (LH) are common sites for lymph node metastases. A commonly reported site of non-malignant FDG uptake on PET imaging in the SR is muscular uptake. PET/CT offers a unique technique to correlate PET findings with CT anatomy in the SR and EH. From September 2002 to March 2003, 147 consecutive clinical patients imaged by FDG PET/CT whole-body scan (GE Discovery LS, CT attenuation correction, OSEM reconstruction) were retrospectively reviewed. The presence of abnormal FDG uptake on PET images in the sites of SR and LH regions was evaluated and the corresponding CT findings on the same regions were also assessed. Results: Of 147 patients, 8 cases (2M, 6F and mean age 44 years) were found with increased symmetrical FDG uptake in the regions of the lower neck and shoulder as well as costo-vertebral articulations, the positive rates were 2.1% and 11.3 % for men and women respectively, and the average rate was 5.4%. However, no FDG uptake was seen in the greater muscular structures of the cervical or thoracic spine. FDG uptake was seen in the fatty tissue between the shoulder muscle and the dorsal thoracic wall, but not within the muscles itself. Five patients (3M, 2F, age 56-74 years,3.4%) showed abnormal LH FDG uptake, which were definitely localized in the vascular structure of the lung hilum by CT Conclusion: Co-registered PET/CT imaging shows that the FDG uptake been well known in the SR and LH regions are not fully located in greater muscular structures and lymph nodes, but in the costo-vertebral articulation complex of the thoracic spine and fatty tissue of the shoulders as well as in the vascular structure of both lung hilum. The FDG uptake in the fatty tissue of the shoulders was mostly seen in women, while the uptake in vascular structure of the lung hilum were

Cell uptake survey of pegylated nanographene oxide.

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Vila, M; Portolés, M T; Marques, P A A P; Feito, M J; Matesanz, M C; Ramírez-Santillán, C; Gonçalves, G; Cruz, S M A; Nieto, A; Vallet-Regi, M

2012-11-23

Graphene and more specifically, nanographene oxide (GO) has been proposed as a highly efficient antitumoral therapy agent. Nevertheless, its cell uptake kinetics, its influence in different types of cells and the possibility of controlling cellular internalization timing, is still a field that remains unexplored. Herein, different cell types have been cultured in vitro for several incubation periods in the presence of 0.075 mg ml(-1) pegylated GO solutions. GO uptake kinetics revealed differences in the agent's uptake amount and speed as a function of the type of cell involved. Osteoblast-like cells GO uptake is higher and faster without resulting in greater cell membrane damage. Moreover, the dependence on the commonly used PEG nature (number of branches) also influences the viability and cell uptake speed. These facts play an important role in the future definition of timing parameters and selective cell uptake control in order to achieve an effective therapy.

Cell uptake survey of pegylated nanographene oxide

International Nuclear Information System (INIS)

Vila, M; Nieto, A; Vallet-Regi, M; Portolés, M T; Feito, M J; Matesanz, M C; Ramírez-Santillán, C; Marques, P A A P; Gonçalves, G; Cruz, S M A

2012-01-01

Graphene and more specifically, nanographene oxide (GO) has been proposed as a highly efficient antitumoral therapy agent. Nevertheless, its cell uptake kinetics, its influence in different types of cells and the possibility of controlling cellular internalization timing, is still a field that remains unexplored. Herein, different cell types have been cultured in vitro for several incubation periods in the presence of 0.075 mg ml −1 pegylated GO solutions. GO uptake kinetics revealed differences in the agent’s uptake amount and speed as a function of the type of cell involved. Osteoblast-like cells GO uptake is higher and faster without resulting in greater cell membrane damage. Moreover, the dependence on the commonly used PEG nature (number of branches) also influences the viability and cell uptake speed. These facts play an important role in the future definition of timing parameters and selective cell uptake control in order to achieve an effective therapy. (paper)

Aerobic metabolism on muscle contraction in porcine gastric smooth muscle.

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Kanda, Hidenori; Kaneda, Takeharu; Nagai, Yuta; Urakawa, Norimoto; Shimizu, Kazumasa

2018-05-18

Exposure to chronic hypoxic conditions causes various gastric diseases, including gastric ulcers. It has been suggested that gastric smooth muscle contraction is associated with aerobic metabolism. However, there are no reports on the association between gastric smooth muscle contraction and aerobic metabolism, and we have investigated this association in the present study. High K + - and carbachol (CCh)-induced muscle contractions involved increasing O 2 consumption. Aeration with N 2 (hypoxia) and NaCN significantly decreased high K + - and CCh-induced muscle contraction and O 2 consumption. In addition, hypoxia and NaCN significantly decreased creatine phosphate (PCr) contents in the presence of high K + . Moreover, decrease in CCh-induced contraction and O 2 consumption was greater than that of high K + . Our results suggest that hypoxia and NaCN inhibit high K + - and CCh-induced contractions in gastric fundus smooth muscles by decreasing O 2 consumption and intracellular PCr content. However, the inhibition of CCh-induced muscle contraction was greater than that of high K + -induced muscle contraction.

Enhancement of glucose uptake in muscular cell by soybean charged peptides isolated by electrodialysis with ultrafiltration membranes (EDUF): activation of the AMPK pathway.

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Roblet, Cyril; Doyen, Alain; Amiot, Jean; Pilon, Geneviève; Marette, André; Bazinet, Laurent

2014-03-15

Soy peptides consumption has been associated with beneficial effects in type 2 diabetes patients. However, the peptide fractions responsible for these effects, and their mechanisms of action, have not been identified yet. In this study, we have isolated soybean peptides by electrodialysis with an ultrafiltration membrane (EDUF) at 50 V/100 kDa, and tested them for their capacity to improve glucose uptake in L6 muscle cells. We observed that these fractions were able to significantly enhance glucose uptake in the presence of insulin. The reported bioactivity would be due to the low molecular weight peptides (300-500 Da) recovered. Moreover, we observed that an enhancement of glucose uptake was correlated to the activation of the AMPK enzyme, well known for its capacity to increase glucose uptake in muscle cells. To our knowledge, this is the first time that bioactive peptides with glucose uptake activity have been isolated from a complex soy matrix, and that the implication of AMPK in it is demonstrated. Copyright © 2013 Elsevier Ltd. All rights reserved.

Enhanced Glycogen Storage of a Subcellular Hot Spot in Human Skeletal Muscle during Early Recovery from Eccentric Contractions

DEFF Research Database (Denmark)

Nielsen, Joachim; Farup, Jean; Rahbek, Stine Klejs

2015-01-01

Unaccustomed eccentric exercise is accompanied by muscle damage and impaired glucose uptake and glycogen synthesis during subsequent recovery. Recently, it was shown that the role and regulation of glycogen in skeletal muscle are dependent on its subcellular localization, and that glycogen synthe...

Physical exercise in aging human skeletal muscle increases mitochondrial calcium uniporter expression levels and affects mitochondria dynamics.

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Zampieri, Sandra; Mammucari, Cristina; Romanello, Vanina; Barberi, Laura; Pietrangelo, Laura; Fusella, Aurora; Mosole, Simone; Gherardi, Gaia; Höfer, Christian; Löfler, Stefan; Sarabon, Nejc; Cvecka, Jan; Krenn, Matthias; Carraro, Ugo; Kern, Helmut; Protasi, Feliciano; Musarò, Antonio; Sandri, Marco; Rizzuto, Rosario

2016-12-01

Age-related sarcopenia is characterized by a progressive loss of muscle mass with decline in specific force, having dramatic consequences on mobility and quality of life in seniors. The etiology of sarcopenia is multifactorial and underlying mechanisms are currently not fully elucidated. Physical exercise is known to have beneficial effects on muscle trophism and force production. Alterations of mitochondrial Ca 2+ homeostasis regulated by mitochondrial calcium uniporter (MCU) have been recently shown to affect muscle trophism in vivo in mice. To understand the relevance of MCU-dependent mitochondrial Ca 2+ uptake in aging and to investigate the effect of physical exercise on MCU expression and mitochondria dynamics, we analyzed skeletal muscle biopsies from 70-year-old subjects 9 weeks trained with either neuromuscular electrical stimulation (ES) or leg press. Here, we demonstrate that improved muscle function and structure induced by both trainings are linked to increased protein levels of MCU Ultrastructural analyses by electron microscopy showed remodeling of mitochondrial apparatus in ES-trained muscles that is consistent with an adaptation to physical exercise, a response likely mediated by an increased expression of mitochondrial fusion protein OPA1. Altogether these results indicate that the ES-dependent physiological effects on skeletal muscle size and force are associated with changes in mitochondrial-related proteins involved in Ca 2+ homeostasis and mitochondrial shape. These original findings in aging human skeletal muscle confirm the data obtained in mice and propose MCU and mitochondria-related proteins as potential pharmacological targets to counteract age-related muscle loss. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Tropomyosin 4 defines novel filaments in skeletal muscle associated with muscle remodelling/regeneration in normal and diseased muscle.

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Vlahovich, Nicole; Schevzov, Galina; Nair-Shaliker, Visalini; Ilkovski, Biljana; Artap, Stanley T; Joya, Josephine E; Kee, Anthony J; North, Kathryn N; Gunning, Peter W; Hardeman, Edna C

2008-01-01

The organisation of structural proteins in muscle into highly ordered sarcomeres occurs during development, regeneration and focal repair of skeletal muscle fibers. The involvement of cytoskeletal proteins in this process has been documented, with nonmuscle gamma-actin found to play a role in sarcomere assembly during muscle differentiation and also shown to be up-regulated in dystrophic muscles which undergo regeneration and repair [Lloyd et al.,2004; Hanft et al.,2006]. Here, we show that a cytoskeletal tropomyosin (Tm), Tm4, defines actin filaments in two novel compartments in muscle fibers: a Z-line associated cytoskeleton (Z-LAC), similar to a structure we have reported previously [Kee et al.,2004], and longitudinal filaments that are orientated parallel to the sarcomeric apparatus, present during myofiber growth and repair/regeneration. Tm4 is upregulated in paradigms of muscle repair including induced regeneration and focal repair and in muscle diseases with repair/regeneration features, muscular dystrophy and nemaline myopathy. Longitudinal Tm4-defined filaments also are present in diseased muscle. Transition of the Tm4-defined filaments from a longitudinal to a Z-LAC orientation is observed during the course of muscle regeneration. This Tm4-defined cytoskeleton is a marker of growth and repair/regeneration in response to injury, disease state and stress in skeletal muscle.

Denervation and high-fat diet reduce insulin signaling in T-tubules in skeletal muscle of living mice

DEFF Research Database (Denmark)

Lauritzen, Hans P M; Ploug, Thorkil; Ai, Hua

2008-01-01

OBJECTIVE: Insulin stimulates muscle glucose transport by translocation of GLUT4 to sarcolemma and T-tubules. Despite muscle glucose uptake playing a major role in insulin resistance and type 2 diabetes, the temporal and spatial changes in insulin signaling and GLUT4 translocation during these co...

Whole-body pre-cooling does not alter human muscle metabolism during sub-maximal exercise in the heat.

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Booth, J; Wilsmore, B R; Macdonald, A D; Zeyl, A; Mcghee, S; Calvert, D; Marino, F E; Storlien, L H; Taylor, N A

2001-06-01

Muscle metabolism was investigated in seven men during two 35 min cycling trials at 60% peak oxygen uptake, at 35 degrees C and 50% relative humidity. On one occasion, exercise was preceded by whole-body cooling achieved by immersion in water during a reduction in temperature from 29 to 24 degrees C, and, for the other trial, by immersion in water at a thermoneutral temperature (control, 34.8 degrees C). Pre-cooling did not alter oxygen uptake during exercise (P > 0.05), whilst the change in cardiac frequency and body mass both tended to be lower following pre-cooling (0.05 whole-body pre-cooling does not alter muscle metabolism during submaximal exercise in the heat. It is more likely that thermoregulatory and cardiovascular strain are reduced, through lower muscle and core temperatures.

Adrenaline and glycogenolysis in skeletal muscle during exercise

DEFF Research Database (Denmark)

Kjaer, M; Howlett, K; Langfort, J

2000-01-01

The role of adrenaline in regulating muscle glycogenolysis and hormone-sensitive lipase (HSL) activity during exercise was examined in six adrenaline-deficient bilaterally adrenalectomised, adrenocortico-hormonal-substituted humans (Adr) and in six healthy control individuals (Con). Subjects cycled...... for 45 min at approximately 70% maximal pulmonary O2 uptake (VO2,max) followed by 15 min at approximately 86% VO2,max either without (-Adr and Con) or with (+Adr) adrenaline infusion that elevated plasma adrenaline levels (45 min, 4.49+/-0.69 nmol l(-1); 60 min, 12.41+/-1.80 nmol l(-1)). Muscle samples...... were obtained at 0, 45 and 60 min of exercise. In -Adr and Con, muscle glycogen was similar at rest (-Adr, 409+/-19 mmol (kg dry wt)(-1); Con, 453+/-24 mmol (kg dry wt)(-1)) and following exercise (-Adr, 237+/-52 mmol (kg dry wt)(-1); Con, 227+/-50 mmol (kg dry wt)(-1)). Muscle lactate, glucose-6...

Muscular involvement by malignant lymphoma: CT and MR findings

International Nuclear Information System (INIS)

Kim, Baek Hyun

2000-01-01

To investigate the CT and MR findings of muscular involvement by malignant lymphoma. Thirteen patients with biopsy-proved muscular involvement by malignant lymphoma were included in this study. Two patients were primary muscle lymphoma and 11 patients were muscle lymphoma by secondary involvement of malignant lymphoma. CT of 10 patients (6 pre-contrast CT and 9 postcontrast CT) and MRI of 6 patients (all with pre a nd post-contrast studies) were retrospectively analyzed. In the majority of patients (84.6%, 11/13), the appearance of muscular involvement was the diffuse enlargement of several muscles as like as a group. The muscles involved by malignant lymphoma showed iso-attenuation (5/6) and homogeneity (6/6) on pre-contrast CT scan, and high attenuation (5/9) or iso-attenuation (4/9) and homogeneity (7/9) on post-contrast CT scan. The signal intensity of involved muscle showed slightly hyper- (4/6) or iso-intense (2/6) and homogeneous (6/6) on T1-weighted images, and hyper-intense (6/6) and homogeneous (4/6) on T2- and Gadolinium-enhanced T1-weighted images. Adjacent bone change was demonstrated in 69.2% (9/13), subcutaneous fat change in 61.5% (8/13), and neurovascular encasement within involved muscle in 53.8% (7/13). The CT and MR findings of muscular involvement by malignant lymphoma were diffuse enlargement of several muscles with homogeneous attenuation or signal intensity, and frequent changes in adjacent bones and subcutaneous fat, or neurovascular encasement. (author)

High-efficiency gene transfer into skeletal muscle mediated by electric pulses

DEFF Research Database (Denmark)

Mir, L M; Bureau, M F; Gehl, J

1999-01-01

Gene delivery to skeletal muscle is a promising strategy for the treatment of muscle disorders and for the systemic secretion of therapeutic proteins. However, present DNA delivery technologies have to be improved with regard to both the level of expression and interindividual variability. We...... report very efficient plasmid DNA transfer in muscle fibers by using square-wave electric pulses of low field strength (less than 300 V/cm) and of long duration (more than 1 ms). Contrary to the electropermeabilization-induced uptake of small molecules into muscle fibers, plasmid DNA has to be present...... in the tissue during the electric pulses, suggesting a direct effect of the electric field on DNA during electrotransfer. This i.m. electrotransfer method increases reporter and therapeutic gene expression by several orders of magnitude in various muscles in mouse, rat, rabbit, and monkey. Moreover, i...

Hypermetabolism of compensatory laryngeal muscles in unilateral vocal cord palsy: comparison study between speech and silence with normal subjects by co-registered PET-CT fusion images

International Nuclear Information System (INIS)

Pai, Moon Sun; Kim, Hyon Kyong; Kim, Han Su; Chung, Sung Min

2005-01-01

There are a few case reports on asymmetric vocal cord uptake on FDG-PET in patients with unilateral vocal cord paralysis, which could be a potential pitfall in the interpretation of FDG-PET images. We evaluated the metabolic activity of laryngeal muscles of patients with unilateral vocal cord paralysis in comparison to normal controls during both speech and silence. Eleven patients with iatrogenic unilateral vocal cord palsy(thyroidectomy 7, lung cancer = 1, others = 3) and 12 normal controls underwent FDG-PET with usual protocol. They were divided into two groups respectively; one group read books aloud for 20 minutes (phonation group) and the other kept silence (non-phonation groups) after FDG injection. Recent neck CT scan were co-registered with FDG-PET to produce PET-CT fusion images to elaborate small laryngeal muscles. In patients with unilateral vocal cord palsy, contralateral non-paralyzed vocal cord showed increased FDG uptake, more intense with phonation group (SUV =5.88, n =5) than non-phonation group (SUV =2.33, n =6) --mainly on thyroarytenoid muscle. Normal control subjects showed symmetric mildly increased FDG uptake (SUV=1.92, n=6) only in phonation group, which was significantly low against patient groups and was localized in lateral cricoarytenoid muscle. Hypermetabolism of contralateral thyroarytenoid muscle in patients with unilateral vocal cord paralysis could be encountered during FDG-PET imaging even with keeping silence. Phonation during FDG-PET study enhance FDG uptake on different laryngeal muscles between unilateral vocal cord paralysis and normal subjects

Transcriptome analysis of skeletal muscle tissue to identify genes involved in pre-slaughter stress response in pigs

Directory of Open Access Journals (Sweden)

Vincenzo Russo

2010-01-01

Full Text Available The knowledge of genes and molecular processes controlling stress reactions and involved in the genetic system determining resistance to stress in pigs could be important for the improvement of meat quality. This research aimed to compare the expression profiles of skeletal muscle between physically stressed and not stressed pigs of different breeds immediately before slaughter. DNA microarray analysis showed that different functional categories of genes are up-regulated in stressed compared to not stressed pigs and relevant differences among breeds were found.

Human skeletal muscle mitochondrial capacity.

Science.gov (United States)

Rasmussen, U F; Rasmussen, H N

2000-04-01

Under aerobic work, the oxygen consumption and major ATP production occur in the mitochondria and it is therefore a relevant question whether the in vivo rates can be accounted for by mitochondrial capacities measured in vitro. Mitochondria were isolated from human quadriceps muscle biopsies in yields of approximately 45%. The tissue content of total creatine, mitochondrial protein and different cytochromes was estimated. A number of activities were measured in functional assays of the mitochondria: pyruvate, ketoglutarate, glutamate and succinate dehydrogenases, palmitoyl-carnitine respiration, cytochrome oxidase, the respiratory chain and the ATP synthesis. The activities involved in carbohydrate oxidation could account for in vivo oxygen uptakes of 15-16 mmol O2 min-1 kg-1 or slightly above the value measured at maximal work rates in the knee-extensor model of Saltin and co-workers, i.e. without limitation from the cardiac output. This probably indicates that the maximal oxygen consumption of the muscle is limited by the mitochondrial capacities. The in vitro activities of fatty acid oxidation corresponded to only 39% of those of carbohydrate oxidation. The maximal rate of free energy production from aerobic metabolism of glycogen was calculated from the mitochondrial activities and estimates of the DeltaG or ATP hydrolysis and the efficiency of the actin-myosin reaction. The resultant value was 20 W kg-1 or approximately 70% of the maximal in vivo work rates of which 10-20% probably are sustained by the anaerobic ATP production. The lack of aerobic in vitro ATP synthesis might reflect termination of some critical interplay between cytoplasm and mitochondria.

Skeletal muscle alterations and exercise performance decrease in erythropoietin-deficient mice: a comparative study

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Mille-Hamard Laurence

2012-06-01

Full Text Available Abstract Background Erythropoietin (EPO is known to improve exercise performance by increasing oxygen blood transport and thus inducing a higher maximum oxygen uptake (VO2max. Furthermore, treatment with (or overexpression of EPO induces protective effects in several tissues, including the myocardium. However, it is not known whether EPO exerts this protective effect when present at physiological levels. Given that EPO receptors have been identified in skeletal muscle, we hypothesized that EPO may have a direct, protective effect on this tissue. Thus, the objectives of the present study were to confirm a decrease in exercise performance and highlight muscle transcriptome alterations in a murine EPO functional knock-out model (the EPO-d mouse. Methods We determined VO2max peak velocity and critical speed in exhaustive runs in 17 mice (9 EPO-d animals and 8 inbred controls, using treadmill enclosed in a metabolic chamber. Mice were sacrificed 24h after a last exhaustive treadmill exercise at critical speed. The tibialis anterior and soleus muscles were removed and total RNA was extracted for microarray gene expression analysis. Results The EPO-d mice’s hematocrit was about 50% lower than that of controls (p  1.4 and 115 were strongly down-regulated (normalized ratio  Conclusions Our results showed that the lack of functional EPO induced a decrease in the aerobic exercise capacity. This decrease was correlated with the hematocrit and reflecting poor oxygen supply to the muscles. The observed alterations in the muscle transcriptome suggest that physiological concentrations of EPO exert both direct and indirect muscle-protecting effects during exercise. However, the signaling pathway involved in these protective effects remains to be described in detail.

Isotopic fractionation during the uptake and elimination of inorganic mercury by a marine fish

International Nuclear Information System (INIS)

Xu, Xiaoyu; Wang, Wen-Xiong

2015-01-01

This study investigated the mass dependent (MDF) and independent fractionation (MIF) of stable mercury isotopes in fish during the uptake and elimination of inorganic species. Mercury accumulation during the exposure led to re-equilibration of organ isotopic compositions with the external sources, and elimination terminated the equilibrating with isotope ratios moving back to the original values. Generally, the isotopic behaviors corresponded to the changes of Hg accumulation in the muscle and liver, causing by the internal transportation, organ redistribution, and mixing of different sources. A small degree of MDF caused by biotransformation of Hg in the liver was documented during the elimination, whereas MIF was not observed. The absence of MIF during geochemical and metabolic processes suggested that mercury isotopes can be used as source tracers. Additionally, fish liver is a more responsive organ than muscle to track Hg source when it is mainly composed of inorganic species. - Highlights: • Isotopic behavior of Hg(II) during the uptake and elimination by a marine fish was studied. • Hg isotopic fractionation in the organ corresponded to the changes of Hg bioaccumulation. • Internal transportation, redistribution and mixing of different sources explained the isotopic changes. • Mass dependent fractionation in the liver was found during Hg elimination. • Liver is more responsive than muscle to track Hg sources using Hg stable isotopes. - Fish liver is a more responsive organ than muscle when mercury stable isotopes are applied to track sources that are mainly composed of inorganic species.

Endoplasmic reticulum stress regulates inflammation and insulin resistance in skeletal muscle from pregnant women.

Science.gov (United States)

Liong, Stella; Lappas, Martha

2016-04-15

Sterile inflammation and infection are key mediators of inflammation and peripheral insulin resistance associated with gestational diabetes mellitus (GDM). Studies have shown endoplasmic reticulum (ER) stress to induce inflammation and insulin resistance associated with obesity and type 2 diabetes, however is paucity of studies investigating the effects of ER stress in skeletal muscle on inflammation and insulin resistance associated with GDM. ER stress proteins IRE1α, GRP78 and XBP-1s were upregulated in skeletal muscle of obese pregnant women, whereas IRE1α was increased in GDM women. Suppression of ER stress, using ER stress inhibitor tauroursodeoxycholic acid (TUDCA) or siRNA knockdown of IRE1α and GRP78, significantly downregulated LPS-, poly(I:C)- or IL-1β-induced production of IL-6, IL-8, IL-1β and MCP-1. Furthermore, LPS-, poly(I:C)- or TNF-α-induced insulin resistance was improved following suppression of ER stress, by increasing insulin-stimulated phosphorylation of IR-β, IRS-1, GLUT-4 expression and glucose uptake. In summary, our inducible obesity and GDM-like models suggests that the development of GDM may be involved in activating ER stress-induced inflammation and insulin resistance in human skeletal muscle. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Comparison of GLUT1, GLUT3, and GLUT4 mRNA and the subcellular distribution of their proteins in normal human muscle

Science.gov (United States)

Stuart, C. A.; Wen, G.; Gustafson, W. C.; Thompson, E. A.

2000-01-01

Basal, "insulin-independent" glucose uptake into skeletal muscle is provided by glucose transporters positioned at the plasma membrane. The relative amount of the three glucose transporters expressed in muscle has not been previously quantified. Using a combination of qualitative and quantitative ribonuclease protection assay (RPA) methods, we found in normal human muscle that GLUT1, GLUT3, and GLUT4 mRNA were expressed at 90 +/- 10, 46 +/- 4, and 156 +/- 12 copies/ng RNA, respectively. Muscle was fractionated by DNase digestion and differential sedimentation into membrane fractions enriched in plasma membranes (PM) or low-density microsomes (LDM). GLUT1 and GLUT4 proteins were distributed 57% to 67% in LDM, whereas GLUT3 protein was at least 88% in the PM-enriched fractions. These data suggest that basal glucose uptake into resting human muscle could be provided in part by each of these three isoforms.

Characterization of bicarbonate-dependent potassium uptake in cultured corneal endothelial cells

International Nuclear Information System (INIS)

Savion, N.; Farzame, N.; Berlin, H.B.

1989-01-01

Bovine corneal endothelial (BCE) cells in culture demonstrated 86Rb+ uptake which was mostly ouabain-sensitive with some (15 to 50%) ouabain-insensitive uptake that was dependent on the presence of bicarbonate in the incubation medium. Bovine smooth muscle (SM) cells demonstrated ouabain-sensitive 86Rb+ uptake but the ouabain-insensitive 86Rb+ uptake was not bicarbonate-dependent. Although omission of bicarbonate from the incubation buffer resulted in some reduction in the pH, this change was not responsible for the reduction in the ouabain-insensitive 86Rb+ uptake. Furthermore, the removal of bicarbonate decreased the 86Rb+ influx but not its efflux. This ouabain-insensitive and bicarbonate-dependent 86Rb+ influx in BCE cells proceeded at a linear rate for at least 60 min and increased as a function of bicarbonate concentration such that almost maximal uptake was observed at a concentration of about 10 to 15 mM. Saturation of the bicarbonate-dependent 86Rb+ pump in BCE cells occurred at a concentration of 2 mM Rb+ in the incubation buffer, similar to the previously observed value for the Na+, K+-ATPase. Competition experiments with both unlabeled Rb+ and K+ demonstrated that likewise in the Na+, K+-ATPase the 86Rb+ influx represented physiological influx of K+. Furthermore, the energy requirements of the bicarbonate-dependent 86Rb+ uptake were similar to those of the 86Rb+ uptake via the Na+, K+-ATPase. The results described in this work demonstrated a novel bicarbonate-dependent K+ pump in addition to the Na+, K+-ATPase pump.(ABSTRACT TRUNCATED AT 250 WORDS)

Involvement of cyclic nucleotides in locust flight muscle metabolism

NARCIS (Netherlands)

Worm, R.A.A.

1980-01-01

1. Flight had no significant effect on the levels of c-AMP of c-GMP in the flight muscles of Locusta migratoria. 2. Injections of 0.01 or 0.1 corpus cardiacum equivalents into the abdominal cavity did not elicit any effect on cyclic nucleotide levels either. 3. Injection of A23187 resulted in

p38 MAPK activation upregulates proinflammatory pathways in skeletal muscle cells from insulin-resistant type 2 diabetic patients

DEFF Research Database (Denmark)

Brown, Audrey E; Palsgaard, Jane; Borup, Rehannah

2015-01-01

Skeletal muscle is the key site of peripheral insulin resistance in type 2 diabetes. Insulin-stimulated glucose uptake is decreased in differentiated diabetic cultured myotubes, which is in keeping with a retained genetic/epigenetic defect of insulin action. We investigated differences in gene...... expression during differentiation between diabetic and control muscle cell cultures. Microarray analysis was performed using skeletal muscle cell cultures established from type 2 diabetic patients with a family history of type 2 diabetes and clinical evidence of marked insulin resistance and nondiabetic...... significantly, it did not improve insulin-stimulated glucose uptake. Increased cytokine expression driven by increased p38 MAPK activation is a key feature of cultured myotubes derived from insulin-resistant type 2 diabetic patients. p38 MAPK inhibition decreased cytokine expression but did not affect...

Muscle-specific expression of hypoxia-inducible factor in human skeletal muscle

DEFF Research Database (Denmark)

Mounier, Rémi; Pedersen, Bente Klarlund; Plomgaard, Peter

2010-01-01

fibres that possess unique patterns of protein and gene expression, producing different capillarization and energy metabolism systems. In this work, we analysed HIF-1alpha mRNA and protein expression related to the fibre-type composition in untrained human skeletal muscle by obtaining muscle biopsies...... from triceps brachii (characterized by a high proportion of type II fibres), from soleus (characterized by a high proportion of type I fibres) and from vastus lateralis (characterized by an equal proportion of type I and II fibres). The hypothesis was that type I muscle fibres would have lower HIF-1......alpha protein level. Interestingly, none of the HIF-1alpha target genes, like the most studied angiogenic factor involved in muscle angiogenesis, vascular endothelial growth factor (VEGF), exhibited a muscle fibre-specific-related mRNA expression at rest in normoxia. However, soleus presented...

Skeletal muscle protein accretion rates and hindlimb growth are reduced in late gestation intrauterine growth-restricted fetal sheep.

Science.gov (United States)

Rozance, Paul J; Zastoupil, Laura; Wesolowski, Stephanie R; Goldstrohm, David A; Strahan, Brittany; Cree-Green, Melanie; Sheffield-Moore, Melinda; Meschia, Giacomo; Hay, William W; Wilkening, Randall B; Brown, Laura D

2018-01-01

Adults who were affected by intrauterine growth restriction (IUGR) suffer from reductions in muscle mass, which may contribute to insulin resistance and the development of diabetes. We demonstrate slower hindlimb linear growth and muscle protein synthesis rates that match the reduced hindlimb blood flow and oxygen consumption rates in IUGR fetal sheep. These adaptations resulted in hindlimb blood flow rates in IUGR that were similar to control fetuses on a weight-specific basis. Net hindlimb glucose uptake and lactate output rates were similar between groups, whereas amino acid uptake was significantly lower in IUGR fetal sheep. Among all fetuses, blood O 2 saturation and plasma glucose, insulin and insulin-like growth factor-1 were positively associated and norepinephrine was negatively associated with hindlimb weight. These results further our understanding of the metabolic and hormonal adaptations to reduced oxygen and nutrient supply with placental insufficiency that develop to slow hindlimb growth and muscle protein accretion. Reduced skeletal muscle mass in the fetus with intrauterine growth restriction (IUGR) persists into adulthood and may contribute to increased metabolic disease risk. To determine how placental insufficiency with reduced oxygen and nutrient supply to the fetus affects hindlimb blood flow, substrate uptake and protein accretion rates in skeletal muscle, late gestation control (CON) (n = 8) and IUGR (n = 13) fetal sheep were catheterized with aortic and femoral catheters and a flow transducer around the external iliac artery. Muscle protein kinetic rates were measured using isotopic tracers. Hindlimb weight, linear growth rate, muscle protein accretion rate and fractional synthetic rate were lower in IUGR compared to CON (P fetal norepinephrine and reduced IGF-1 and insulin. © 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.

Free fatty acid has a negative correlation with myocardial uptake of FDG

Energy Technology Data Exchange (ETDEWEB)

Eo, Jae Seon; Lee, Won Woo; Park, Eun Kyung; So, Young; Lee, Dong Soo; Chung, June Key; Lee, Myung Chul; Kim, Sang Eun [College of Medicine, Seoul National University, Seoul (Korea, Republic of)

2004-07-01

Free fatty acid (FFA) is a marker of insulin resistance. Myocardial uptake of FDG is influenced by insulin resistance. We investigated the correlation of FFA and myocardial uptake of FDG in whole body PET. We measured serum FFA levels in consecutive 112 patients who underwent whole body FDG PET due to malignancy work up. Twelve patients with diabetes. 13 with liver disease, 4 with suspicious ischemic heart disease. 1 with steroid therapy, and 10 with final diagnosis of benign disease were excluded. After fasting of diet or beverages for at least 6 hours, blood was aspirated at peripheral vein for measurement of FFA and glucose in serum. FDG was injected as a dose of 0.14 mCi/kg body weight. Fifty minutes later, whole body PET scan was performed from skull base to upper thigh. Maximum SUV (maxSUV) using lean body weight was obtained in heart. liver, cerebellum, muscle and malignant tissues. Finally 72 patients (M:F 45:27, age 56.9{+-}15.8 years) were enrolled. There were 27 non small cell lung cancer, 14 lymphoma, 10 esophageal cancer, 3 breast cancer, 3 colon cancer, 3 renal cell cancer, 2 melanoma, and 10 other cancers. Serum glucose level was 96.6{+-}14.3 mg/dL. Serum FFA level was 720.0{+-}315.2 uEq/L. MaxSUV of main malignant tissue ranged from 0.7 to 11.5 (mean 4.9{+-}2.6). MaxSUV of each organs were 1.0 to 14.6 (mean 4.0{+-}3.0) in heart, 2.7 to 6.4 (mean 3.9{+-}0.6) in cerebellum, 1.0 to 2.6 (mean 1.9{+-}0.3) in liver, and 0.6 to 1.1 (mean 0.8{+-}0.1) in gluteal muscle. FFA and maxSUV of heart had a negative correlation. The best fitting line was MaxSUV of Heart = -4.4583 x In(FF A) + 32.964. But FFA had no correlation with any other parameters like serum glucose level, and MaxSUV of cerebellum, muscle, liver and malignant tissues. We found a negative correlation between FFA levels and myocardial uptake of FDG. FFA modifying drugs such as nicotinic acid derivatives may have influence on myocardial uptake of FDG.

Uptake and utilization of nutrients by developing kernels of Zea mays L

International Nuclear Information System (INIS)

Lyznik, L.A.

1987-01-01

The mechanisms involved in amino acid and sugar uptake by developing maize kernels were investigated. In the pedicel region of maize kernel, the site of nutrient unloading from phloem terminals, amino acids are accumulated in considerable amounts and undergo significant interconversion. A wide spectrum of enzymatic activities involved in the metabolism of amino acids is observed in these tissues. Subsequently, amino acids are taken up by the endosperm tissue in processes which require energy and the presence of carrier proteins. Conversely, no evidence was found that energy and carriers are involved in sugar uptake. This process of sugar uptake is not inhibited by metabolic inhibitors and shows nonsaturable kinetics, but the uptake is pH-dependent. L-glucose is taken up at a significantly reduced rate in comparison to D-glucose uptake. Based on analysis of radioactivity distribution among sugar fractions after incubations of kernels with radiolabeled D-glucose, it seems that sucrose is not efficiently resynthesized from D-glucose in the endosperm tissue. Thus, the proposed mechanism of sucrose transport involving sucrose hydrolysis in the pedicel region and subsequent resynthesis in endosperm cells may not be the main pathway. The evidence that transfer cells play an active role in D-glucose transport is presented

Skeletal muscle lymphoma: observations at MR imaging

International Nuclear Information System (INIS)

Eustace, S.; Winalski, C.S.; McGowen, A.; Lan, H.; Dorfman, D.

1996-01-01

We present the MR appearances of three patients with biopsy-proven primary lymphoma of skeletal muscle. In each case lymphoma resulted in bulky expansion of the involved muscle, homogeneously isointense to skeletal muscle on T1-weighted images, homogeneously hyperintense to skeletal muscle on T2-weighted images and diffusely enhancing following intravenous administration of gadopentate dimeglumine. (orig.)

Resistance training, insulin sensitivity and muscle function in the elderly

DEFF Research Database (Denmark)

Dela, Flemming; Kjaer, Michael

2006-01-01

Ageing is associated with a loss in both muscle mass and in the metabolic quality of skeletal muscle. This leads to sarcopenia and reduced daily function, as well as to an increased risk for development of insulin resistance and type 2 diabetes. A major part, but not all, of these changes......, and likewise to improve muscle strength in both elderly healthy individuals and in elderly individuals with chronic disease. The increased strength is coupled to improved function and a decreased risk for fall injuries and fractures. Elderly individuals have preserved the capacity to improve muscle strength...... are associated with an age-related decrease in the physical activity level and can be counteracted by increased physical activity of a resistive nature. Strength training has been shown to improve insulin-stimulated glucose uptake in both healthy elderly individuals and patients with manifest diabetes...

Training-induced adaptation of oxidative phosphorylation in skeletal muscles.

Science.gov (United States)

Korzeniewski, Bernard; Zoladz, Jerzy A

2003-08-15

Muscle training/conditioning improves the adaptation of oxidative phosphorylation in skeletal muscles to physical exercise. However, the mechanisms underlying this adaptation are still not understood fully. By quantitative analysis of the existing experimental results, we show that training-induced acceleration of oxygen-uptake kinetics at the onset of exercise and improvement of ATP/ADP stability due to physical training are mainly caused by an increase in the amount of mitochondrial proteins and by an intensification of the parallel activation of ATP usage and ATP supply (increase in direct stimulation of oxidative phosphorylation complexes accompanying stimulation of ATP consumption) during exercise.

Sustained benefit of temporary limited reperfusion in skeletal muscle following ischemia

International Nuclear Information System (INIS)

Anderson, R.J.; Cambria, R.; Kerr, J.; Hobson, R.W. II

1990-01-01

Limiting the rate of reperfusion blood flow following prolonged ischemia in skeletal muscle has been shown beneficial. However, the persistence of this benefit with reinstitution of normal blood flow remains undefined. We investigated the role of temporary limited reperfusion on ischemia-reperfusion injury in an isolated gracilis muscle model in six anesthetized dogs. Both gracilis muscles were subjected to 6 hr of ischemia followed by 2 hr of reperfusion. Reperfusion blood flow was limited for the first hour in one gracilis muscle to its preischemic rate followed by a second hour of normal reperfusion (LR/NR). The contralateral muscle underwent 2 hr of normal reperfusion (NR/NR). Muscle injury was quantified by technetium-99m pyrophosphate (TcPyp) uptake and by histochemical staining using triphenyltetrazolium chloride (TTC) with planimetry of the infarct size. Capillary permeability was evaluated by muscle weight gain. Results are reported as the mean +/- SEM. These data demonstrate a sustained benefit from temporary limited reperfusion. This methodology should be considered in the surgical management of the acutely ischemic limb

Evidence for a plasma-membrane-bound nitrate reductase involved in nitrate uptake of Chlorella sorokiniana

Science.gov (United States)

Tischner, R.; Ward, M. R.; Huffaker, R. C.

1989-01-01

Anti-nitrate-reductase (NR) immunoglobulin-G (IgG) fragments inhibited nitrate uptake into Chlorella cells but had no affect on nitrate uptake. Intact anti-NR serum and preimmune IgG fragments had no affect on nitrate uptake. Membrane-associated NR was detected in plasma-membrane (PM) fractions isolated by aqueous two-phase partitioning. The PM-associated NR was not removed by sonicating PM vesicles in 500 mM NaCl and 1 mM ethylenediaminetetraacetic acid and represented up to 0.8% of the total Chlorella NR activity. The PM NR was solubilized by Triton X-100 and inactivated by Chlorella NR antiserum. Plasma-membrane NR was present in ammonium-grown Chlorella cells that completely lacked soluble NR activity. The subunit sizes of the PM and soluble NRs were 60 and 95 kDa, respectively, as determined by sodium-dodecyl-sulfate electrophoresis and western blotting.

Molecular mechanism by which AMP-activated protein kinase activation promotes glycogen accumulation in muscle

DEFF Research Database (Denmark)

Hunter, Roger W; Treebak, Jonas Thue; Wojtaszewski, Jørgen

2011-01-01

AND METHODS We recently generated knock-in mice in which wild-type muscle GS was replaced by a mutant (Arg582Ala) that could not be activated by glucose-6-phosphate (G6P), but possessed full catalytic activity and could still be activated normally by dephosphorylation. Muscles from GS knock-in or transgenic......-insensitive GS knock-in mice, although AICAR-stimulated AMPK activation, glucose transport, and total glucose utilization were normal. CONCLUSIONS We provide genetic evidence that AMPK activation promotes muscle glycogen accumulation by allosteric activation of GS through an increase in glucose uptake...

Contribution of liver and skeletal muscle to alanine and lactate metabolism in humans

International Nuclear Information System (INIS)

Consoli, A.; Nurjhan, N.; Reilly, J.J. Jr.; Bier, D.M.; Gerich, J.E.

1990-01-01

To quantitate alanine and lactate gluconeogenesis in postabsorptive humans and to test the hypothesis that muscle is the principal source of these precursors, we infused normal volunteers with [3-14C]lactate, [3-13C]alanine, and [6-3H]glucose and calculated alanine and lactate incorporation into plasma glucose corrected for tricarboxylic acid cycle carbon exchange, the systemic appearance of these substrates, and their forearm fractional extraction, uptake, and release. Forearm alanine and lactate fractional extraction averaged 37 +/- 3 and 27 +/- 2%, respectively; muscle alanine release (2.94 +/- 0.27 mumol.kg body wt-1.min-1) accounted for approximately 70% of its systemic appearance (4.18 +/- 0.31 mumol.kg body wt-1.min-1); muscle lactate release (5.51 +/- 0.42 mumol.kg body wt-1.min-1) accounted for approximately 40% of its systemic appearance (12.66 +/- 0.77 mumol.kg body wt-1.min-1); muscle alanine and lactate uptake (1.60 +/- 0.7 and 3.29 +/- 0.36 mumol.kg body wt-1.min-1, respectively) accounted for approximately 30% of their overall disappearance from plasma, whereas alanine and lactate incorporation into plasma glucose (1.83 +/- 0.20 and 4.24 +/- 0.44 mumol.kg body wt-1.min-1, respectively) accounted for approximately 50% of their disappearance from plasma. We therefore conclude that muscle is the major source of plasma alanine and lactate in postabsorptive humans and that factors regulating their release from muscle may thus exert an important influence on hepatic gluconeogenesis

Structure–function relationship of skeletal muscle provides inspiration for design of new artificial muscle

International Nuclear Information System (INIS)

Gao, Yingxin; Zhang, Chi

2015-01-01

A variety of actuator technologies have been developed to mimic biological skeletal muscle that generates force in a controlled manner. Force generation process of skeletal muscle involves complicated biophysical and biochemical mechanisms; therefore, it is impossible to replace biological muscle. In biological skeletal muscle tissue, the force generation of a muscle depends not only on the force generation capacity of the muscle fiber, but also on many other important factors, including muscle fiber type, motor unit recruitment, architecture, structure and morphology of skeletal muscle, all of which have significant impact on the force generation of the whole muscle or force transmission from muscle fibers to the tendon. Such factors have often been overlooked, but can be incorporated in artificial muscle design, especially with the discovery of new smart materials and the development of innovative fabrication and manufacturing technologies. A better understanding of the physiology and structure–function relationship of skeletal muscle will therefore benefit the artificial muscle design. In this paper, factors that affect muscle force generation are reviewed. Mathematical models used to model the structure–function relationship of skeletal muscle are reviewed and discussed. We hope the review will provide inspiration for the design of a new generation of artificial muscle by incorporating the structure–function relationship of skeletal muscle into the design of artificial muscle. (topical review)

Structure-function relationship of skeletal muscle provides inspiration for design of new artificial muscle

Science.gov (United States)

Gao, Yingxin; Zhang, Chi

2015-03-01

A variety of actuator technologies have been developed to mimic biological skeletal muscle that generates force in a controlled manner. Force generation process of skeletal muscle involves complicated biophysical and biochemical mechanisms; therefore, it is impossible to replace biological muscle. In biological skeletal muscle tissue, the force generation of a muscle depends not only on the force generation capacity of the muscle fiber, but also on many other important factors, including muscle fiber type, motor unit recruitment, architecture, structure and morphology of skeletal muscle, all of which have significant impact on the force generation of the whole muscle or force transmission from muscle fibers to the tendon. Such factors have often been overlooked, but can be incorporated in artificial muscle design, especially with the discovery of new smart materials and the development of innovative fabrication and manufacturing technologies. A better understanding of the physiology and structure-function relationship of skeletal muscle will therefore benefit the artificial muscle design. In this paper, factors that affect muscle force generation are reviewed. Mathematical models used to model the structure-function relationship of skeletal muscle are reviewed and discussed. We hope the review will provide inspiration for the design of a new generation of artificial muscle by incorporating the structure-function relationship of skeletal muscle into the design of artificial muscle.

Muscle MRI in pediatrics: clinical, pathological and genetic correlation

Energy Technology Data Exchange (ETDEWEB)

Cejas, Claudia P.; Serra, Maria M.; Galvez, David F.G. [Foundation for Neurological Research Dr. Raul Carrea (FLENI), Radiology Department, Buenos Aires (Argentina); Cavassa, Eliana A.; Vazquez, Gabriel A.; Massaro, Mario E.L.; Schteinschneider, Angeles V. [Foundation for Neurological Research Dr. Raul Carrea (FLENI), Department of Neuropediatrics, Buenos Aires (Argentina); Taratuto, Ana L. [Foundation for Neurological Research Dr. Raul Carrea (FLENI), Neuropathology Consultant, Buenos Aires (Argentina)

2017-05-15

Pediatric myopathies comprise a very heterogeneous group of disorders that may develop at different ages and affect different muscle groups. Its diagnosis is sometimes difficult and must be confirmed by muscle biopsy and/or genetic analysis. In recent years, muscle involvement patterns observed on MRI have become a valuable tool, aiding clinical diagnosis and enriching pathological and genetic assessments. We selected eight myopathy cases from our institutional database in which the pattern of muscle involvement observed on MRI was almost pathognomonic and could therefore contribute to establishing diagnosis. Muscle biopsy, genetic diagnosis or both confirmed all cases. (orig.)

Muscle MRI in pediatrics: clinical, pathological and genetic correlation

International Nuclear Information System (INIS)

Cejas, Claudia P.; Serra, Maria M.; Galvez, David F.G.; Cavassa, Eliana A.; Vazquez, Gabriel A.; Massaro, Mario E.L.; Schteinschneider, Angeles V.; Taratuto, Ana L.

2017-01-01

Pediatric myopathies comprise a very heterogeneous group of disorders that may develop at different ages and affect different muscle groups. Its diagnosis is sometimes difficult and must be confirmed by muscle biopsy and/or genetic analysis. In recent years, muscle involvement patterns observed on MRI have become a valuable tool, aiding clinical diagnosis and enriching pathological and genetic assessments. We selected eight myopathy cases from our institutional database in which the pattern of muscle involvement observed on MRI was almost pathognomonic and could therefore contribute to establishing diagnosis. Muscle biopsy, genetic diagnosis or both confirmed all cases. (orig.)

MicroRNA in Skeletal Muscle: Its Crucial Roles in Signal Proteins, Mus cle Fiber Type, and Muscle Protein Synthesis.

Science.gov (United States)

Zhang, Jing; Liu, Yu Lan

2017-01-01

Pork is one of the most economical sources of animal protein for human consumption. Meat quality is an important economic trait for the swine industry, which is primarily determined by prenatal muscle development and postnatal growth. Identification of the molecular mechanisms underlying skeletal muscle development is a key priority. MicroRNAs (miRNAs) are a class of small noncoding RNAs that have emerged as key regulators of skeletal muscle development. A number of muscle-related miRNAs have been identified by functional gain and loss experiments in mouse model. However, determining miRNA-mRNA interactions involved in pig skeletal muscle still remains a significant challenge. For a comprehensive understanding of miRNA-mediated mechanisms underlying muscle development, miRNAome analyses of pig skeletal muscle have been performed by deep sequencing. Additionally, porcine miRNA single nucleotide polymorphisms have been implicated in muscle fiber types and meat quality. The present review provides an overview of current knowledge on recently identified miRNAs involved in myogenesis, muscle fiber type and muscle protein metabolism. Undoubtedly, further systematic understanding of the functions of miRNAs in pig skeletal muscle development will be helpful to expand the knowledge of basic skeletal muscle biology and be beneficial for the genetic improvement of meat quality traits. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

In-vivo tissue uptake and retention of Sn-117m(4+)DTPA in a human subject with metastatic bone pain and in normal mice

International Nuclear Information System (INIS)

Swailem, Fayez M.; Krishnamurthy, Gerbail T.; Srivastava, Suresh C.; Aguirre, Maria L.; Ellerson, Dawn L.; Walsh, T. Kent; Simpson, Laura

1998-01-01

Organ and tissue uptake and retention of Sn-117m(4+)DTPA were studied in a human subject treated for metastatic bone pain, and the results were compared with the biodistribution studies in five normal mice. The explanted organs from a patient who received a therapy dose of 18.6 mCi (688.2 MBq) Sn-117m(4+)DTPA and who died 47 days later were imaged with a γ-camera, and tissue samples were counted and also autoradiographed. Bone, muscle, liver, fat, lungs, kidneys, spleen, heart and pancreas tissue samples were assayed in a well counter for radioactivity. Regions of interest were drawn over bone and major organs to calculate and quantify clearance times using three in vivo Sn-117m(4+)DTPA whole-body scintigrams acquired at 1, 24 and 168 h after injection. Five normal mice injected with the same batch of Sn-117m(4+)DTPA as used for the human subject were sacrificed at 24 h, and tissue samples were collected and assayed for radioactivity for comparison with the human data. For the human subject, whole-body retention at 47 days postinjection was 81% of the injected dose, and the rest (19%) was excreted in urine. Of the whole-body retained activity at 47 days, 82.4% was in bone, 7.8% in the muscle and 1.5% in the liver, and the rest was distributed among other tissues. γ-Ray scintigrams and electron autoradiographs of coronal slices of the thoracolumbar vertebral body showed heterogenous metastatic involvement with normal bone between metastatic lesions. There was nonuniform distribution of radioactivity even within a single vertebral body, indicating normal bone between metastatic lesions. Lesion-to-nonlesion ratios ranged from 3 to 5. However, the osteoid-to-marrow cavity deposition ratio, from the microautoradiographs, was 11:1. The peak uptake in the human bone was seen at 137 h with no biological clearance. Soft tissues showed peak uptake at 1 h and exhibited three compartmental clearance components. Whole-body retention in normal mice was 38.7% of the injected

Ameliorative effects of polyunsaturated fatty acids against palmitic acid-induced insulin resistance in L6 skeletal muscle cells

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Sawada Keisuke

2012-03-01

Full Text Available Abstract Background Fatty acid-induced insulin resistance and impaired glucose uptake activity in muscle cells are fundamental events in the development of type 2 diabetes and hyperglycemia. There is an increasing demand for compounds including drugs and functional foods that can prevent myocellular insulin resistance. Methods In this study, we established a high-throughput assay to screen for compounds that can improve myocellular insulin resistance, which was based on a previously reported non-radioisotope 2-deoxyglucose (2DG uptake assay. Insulin-resistant muscle cells were prepared by treating rat L6 skeletal muscle cells with 750 μM palmitic acid for 14 h. Using the established assay, the impacts of several fatty acids on myocellular insulin resistance were determined. Results In normal L6 cells, treatment with saturated palmitic or stearic acid alone decreased 2DG uptake, whereas unsaturated fatty acids did not. Moreover, co-treatment with oleic acid canceled the palmitic acid-induced decrease in 2DG uptake activity. Using the developed assay with palmitic acid-induced insulin-resistant L6 cells, we determined the effects of other unsaturated fatty acids. We found that arachidonic, eicosapentaenoic and docosahexaenoic acids improved palmitic acid-decreased 2DG uptake at lower concentrations than the other unsaturated fatty acids, including oleic acid, as 10 μM arachidonic acid showed similar effects to 750 μM oleic acid. Conclusions We have found that polyunsaturated fatty acids, in particular arachidonic and eicosapentaenoic acids prevent palmitic acid-induced myocellular insulin resistance.

Effects of the belt electrode skeletal muscle electrical stimulation system on lower extremity skeletal muscle activity: Evaluation using positron emission tomography.

Science.gov (United States)

Numata, Hitoaki; Nakase, Junsuke; Inaki, Anri; Mochizuki, Takafumi; Oshima, Takeshi; Takata, Yasushi; Kinuya, Seigo; Tsuchiya, Hiroyuki

2016-01-01

Lower-extremity muscle weakness in athletes after lower limb trauma or surgery can hinder their return to sports, and the associated muscle atrophy may lead to deterioration in performance after returning to sports. Recently, belt electrode skeletal muscle electrical stimulation (B-SES) which can contract all the lower limb skeletal muscles simultaneously was developed. However, no study has evaluated skeletal muscle activity with B-SES. Since only superficial muscles as well as a limited number of muscles can be investigated using electromyography, we investigated whether positron emission tomography (PET) can evaluate the activity of all the skeletal muscles in the body simultaneously. The purpose of this study was to evaluate the effectiveness of the B-SES system using PET. Twelve healthy males (mean age, 24.3 years) were divided into two groups. The subjects in the control group remained in a sitting position for 10 min, and [(18)F] fluorodeoxyglucose (FDG) was intravenously injected. In the exercise group, subjects exercised using the B-SES system for 20 min daily for three consecutive days as a pre-test exercise. On the measurement day, they exercised for 10 min, received an injection of FDG, and exercised for another 10 min. PET-computed tomography images were obtained in each group 60 min after the FDG injection. Regions of interest were drawn in each lower-extremity muscle. We compared each skeletal muscle metabolism using the standardized uptake value. In the exercise group, FDG accumulation in the gluteus maximus, gluteus medius, gluteus minimus, quadriceps femoris, sartorius, and hamstrings was significantly higher than the muscles in the control (P skeletal muscle activity of the gluteal muscles as well as the most lower-extremity muscles simultaneously. Copyright © 2015 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.

Pain severity is associated with muscle strength and peak oxygen uptake in adults with fibromyalgia

Directory of Open Access Journals (Sweden)

Hooten WM

2014-05-01

Full Text Available W Michael Hooten,1,2 Jolene M Smith,3 Jason S Eldrige,1 David A Olsen,3 W David Mauck,1 Susan M Moeschler11Department of Anesthesiology, 2Department of Psychiatry and Psychology, Mayo Clinic College of Medicine, 3Mayo School of Graduate Medical Education, Rochester, MN, USABackground: The associations between pain, lower extremity strength, and aerobic conditioning have not been widely investigated in adults with fibromyalgia (FM. The principle objective of this study was to investigate the relationship between pain severity and knee strength in patients seeking treatment for FM. A secondary objective was to investigate the relationship between pain scores and aerobic conditioning.Methods: Three measures of knee strength (isokinetic extensor, isokinetic flexor, isometric extensor were quantified in the dominant leg of 69 adults with FM using a dynamometer at speeds of 60 degrees per second (60°/s and 180°/s. Peak oxygen uptake (VO2 was assessed using a cycle ergometer, and pain was assessed using the pain severity subscale of the Multidimensional Pain Inventory.Results: In univariable linear regression analyses using pain severity as the dependent variable, lesser values of isokinetic knee extensor strength at 60°/s (P=0.041 and 180°/s (P=0.010, isokinetic knee flexor strength at 60°/s (P=0.028 and 180°/s (P=0.003, and peak VO2 uptake (P=0.031 were predictive of greater pain severity scores. In multiple variable linear regression models adjusted for age, sex, body mass index, and opioid use, the following associations retained statistical significance; isokinetic knee extensor strength at 60°/s (P=0.020 and 180°/s (P=0.003, isokinetic knee flexor strength at 60°/s (P=0.015 and 180°/s (P=0.001, and peak VO2 uptake (P=0.014. However, no significant associations were found between pain severity and isometric knee extensor strength.Conclusion: The main findings from this study were that lesser values of isokinetic knee strength and peak VO

Changes in uptake of 3H-progesterone by female rat brain and pituitary from birth to sexual maturity

International Nuclear Information System (INIS)

Presl, J.; Figarova, V.; Herzmann, J.; Roehling, S.

1975-01-01

3 H-progesterone uptake by various parts of the brain, pituitary and skeletal muscle was compared in newborn, 5-, 10-, 15-, 20-, 25-and 50-day-old female rats at 1 hr after a single intraperitoneal injection of 50 μCi/100 g body weight. High uptake values in newborn animals and in those aged 5 days were found in all tissues investigated. A sharp decrease in accumulation was observed from birth and/or 5th day of life. The uptake by the pituitary was higher than those by other tissues investigated. The ratio of radioactivity concentration between the tissues and the cerebellar cortex increased significantly only in the posterior hypothalamus of adult females (at the age of 50 days). In the pituitary the ratio tissue/cortex was already significantly higher in newborns. The high level of brain radioactivity in the youngest animals probably was a manifestation of high plasma concentrations of the tritiated progesterone. The striking decrease in the uptake of radioactivity by the brain and pituitary during the first two weeks of life most likely reflected a decreased level of plasma radioactivity, as shown indirectly by the concomitant decrease in the labelled progesterone uptake by the skeletal muscle. The increase in the tissue/cortex ratio in the posterior hypothalamus with the attainment of sexual maturity suggested the first appearance of a specific binding capacity for the progesterone which is present in the pituitary since birth. (author) assumed to be

Age-related differences in skeletal muscle microvascular response to exercise as detected by contrast-enhanced ultrasound (CEUS.

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Wulf Hildebrandt

Full Text Available Aging involves reductions in exercise total limb blood flow and exercise capacity. We hypothesized that this may involve early age-related impairments of skeletal muscle microvascular responsiveness as previously reported for insulin but not for exercise stimuli in humans.Using an isometric exercise model, we studied the effect of age on contrast-enhanced ultrasound (CEUS parameters, i.e. microvascular blood volume (MBV, flow velocity (MFV and blood flow (MBF calculated from replenishment of Sonovue contrast-agent microbubbles after their destruction. CEUS was applied to the vastus lateralis (VLat and intermedius (VInt muscle in 15 middle-aged (MA, 43.6±1.5 years and 11 young (YG, 24.1±0.6 years healthy males before, during, and after 2 min of isometric knee extension at 15% of peak torque (PT. In addition, total leg blood flow as recorded by femoral artery Doppler-flow. Moreover, fiber-type-specific and overall capillarisation as well as fiber composition were additionally assessed in Vlat biopsies obtained from CEUS site. MA and YG had similar quadriceps muscle MRT-volume or PT and maximal oxygen uptake as well as a normal cardiovascular risk factors and intima-media-thickness.During isometric exercise MA compared to YG reached significantly lower levels in MFV (0.123±0.016 vs. 0.208±0.036 a.u. and MBF (0.007±0.001 vs. 0.012±0.002 a.u.. In the VInt the (post-occlusive hyperemia post-exercise peaks in MBV and MBF were significantly lower in MA vs. YG. Capillary density, capillary fiber contacts and femoral artery Doppler were similar between MA and YG.In the absence of significant age-related reductions in capillarisation, total leg blood flow or muscle mass, healthy middle-aged males reveal impaired skeletal muscle microcirculatory responses to isometric exercise. Whether this limits isometric muscle performance remains to be assessed.