Global skeletal uptake of technetium-99m methylene diphosphonate in female patients receiving suppressive doses of L-thyroxine for differentiated thyroid cancer

International Nuclear Information System (INIS)

Frusciante, V.; Dicembrino, F.; Carnevale, V.; Scillitani, A.; Zingrillo, M.; Ghiggi, M.R.; Giannatempo, G.M.; Minisola, S.

1998-01-01

This study was carried out in order to investigate the possible detrimental effects on bone of levothyroxine (l-T 4 ) suppressive therapy in female patients who had undergone surgery for differentiated thyroid cancer (DTC). Twenty female (14 premenopausal and 6 postmenopausal) patients receiving l-T 4 suppressive therapy for DTC were studied. The sample was selected in such a way as to avoid factors influencing bone metabolism other than l-T 4 . All patients were monitored by sensitive thyroid-stimulating hormone, free triiodothyronine and free thyroxine assays throughout the follow-up. Nineteen healthy (12 premenopausal and 7 postmenopausal) matched women served as controls. In all subjects bone turnover was evaluated by the measurement of global skeletal uptake of technetium-99m methylene diphosphonate (GSU); bone mineral density (BMD) was measured by quantitative computed tomography at the lumbar spine (LS) and by dual-energy X-ray absorptiometry both at the LS and at three femoral sites: the femoral neck, Ward's triangle and the greater trochanter. No significant difference was found in either GSU or BMD between patients (treated for an average period of 68 months) and controls in the whole sample or in any subgroup. Furthermore, no correlations were found between either GSU or BMD and the duration of therapy, daily doses of l-T 4 or results of thyroid function tests. Our data show that carefully monitored l-T 4 therapy does not influence skeletal turnover (directly reflected by GSU) or the bone density of the spine and femur. (orig.)

Global skeletal uptake of technetium-99m methylene diphosphonate in female patients receiving suppressive doses of L-thyroxine for differentiated thyroid cancer

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Frusciante, V.; Dicembrino, F. [Department of Nuclear Medicine, Ospedale ``Casa Sollievo della Sofferenza``, IRCCS di San Giovanni Rotondo (Italy); Carnevale, V. [Division of Internal Medicine, Ospedale ``Casa Sollievo della Sofferenza``, IRCCS di San Giovanni Rotondo (Italy); Scillitani, A.; Zingrillo, M.; Ghiggi, M.R. [Division of Endocrinology, Ospedale ``Casa Sollievo della Sofferenza``, IRCCS di San Giovanni Rotondo (Italy); Giannatempo, G.M. [Department of Radiology, Ospedale ``Casa Sollievo della Sofferenza``, IRCCS di San Giovanni Rotondo (Italy); Minisola, S. [Istituto di II Clinica Medica, Universita degli Studi di Roma ``La Sapienza``, Rome (Italy)

1998-02-01

This study was carried out in order to investigate the possible detrimental effects on bone of levothyroxine (l-T{sub 4}) suppressive therapy in female patients who had undergone surgery for differentiated thyroid cancer (DTC). Twenty female (14 premenopausal and 6 postmenopausal) patients receiving l-T{sub 4} suppressive therapy for DTC were studied. The sample was selected in such a way as to avoid factors influencing bone metabolism other than l-T{sub 4}. All patients were monitored by sensitive thyroid-stimulating hormone, free triiodothyronine and free thyroxine assays throughout the follow-up. Nineteen healthy (12 premenopausal and 7 postmenopausal) matched women served as controls. In all subjects bone turnover was evaluated by the measurement of global skeletal uptake of technetium-99m methylene diphosphonate (GSU); bone mineral density (BMD) was measured by quantitative computed tomography at the lumbar spine (LS) and by dual-energy X-ray absorptiometry both at the LS and at three femoral sites: the femoral neck, Ward`s triangle and the greater trochanter. No significant difference was found in either GSU or BMD between patients (treated for an average period of 68 months) and controls in the whole sample or in any subgroup. Furthermore, no correlations were found between either GSU or BMD and the duration of therapy, daily doses of l-T{sub 4} or results of thyroid function tests. Our data show that carefully monitored l-T{sub 4} therapy does not influence skeletal turnover (directly reflected by GSU) or the bone density of the spine and femur. (orig.) With 1 fig., 2 tabs., 36 refs.

Skeletal muscle glucose uptake during contraction is regulated by nitric oxide and ROS independently of AMPK.

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Merry, Troy L; Steinberg, Gregory R; Lynch, Gordon S; McConell, Glenn K

2010-03-01

Reactive oxygen species (ROS) and nitric oxide (NO) have been implicated in the regulation of skeletal muscle glucose uptake during contraction, and there is evidence that they do so via interaction with AMP-activated protein kinase (AMPK). In this study, we tested the hypothesis that ROS and NO regulate skeletal muscle glucose uptake during contraction via an AMPK-independent mechanism. Isolated extensor digitorum longus (EDL) and soleus muscles from mice that expressed a muscle-specific kinase dead AMPKalpha2 isoform (AMPK-KD) and wild-type litter mates (WT) were stimulated to contract, and glucose uptake was measured in the presence or absence of the antioxidant N-acetyl-l-cysteine (NAC) or the nitric oxide synthase (NOS) inhibitor N(G)-monomethyl-l-arginine (l-NMMA). Contraction increased AMPKalpha2 activity in WT but not AMPK-KD EDL muscles. However, contraction increased glucose uptake in the EDL and soleus muscles of AMPK-KD and WT mice to a similar extent. In EDL muscles, NAC and l-NMMA prevented contraction-stimulated increases in oxidant levels (dichloroflourescein fluorescence) and NOS activity, respectively, and attenuated contraction-stimulated glucose uptake in both genotypes to a similar extent. In soleus muscles of AMPK-KD and WT mice, NAC prevented contraction-stimulated glucose uptake and l-NMMA had no effect. This is likely attributed to the relative lack of neuronal NOS in the soleus muscles compared with EDL muscles. Contraction increased AMPKalpha Thr(172) phosphorylation in EDL and soleus muscles of WT but not AMPK-KD mice, and this was not affected by NAC or l-NMMA treatment. In conclusion, ROS and NO are involved in regulating skeletal muscle glucose uptake during contraction via an AMPK-independent mechanism.

The mechanism of uptake of bone-seeking isotopes by skeletal metastases

International Nuclear Information System (INIS)

Galasko, C.S.B.

1977-01-01

Although skeletal scintigraphy has become accepted as an extremely useful method of examining the skeleton, particularly for the early detection of skeletal metastases and the assessment of their response to therapy, the underlying pathological changes which allow this use of isotopes are not well understood. This study was undertaken in man and in the experimental animal in an attempt to explain the underlying mechanism for skeletal scintigraphy. Autopsy specimens indicated that tumour invasion of bone, with the possible exception of lymphomata, is associated with a significant increase in new bone production, shown by an increase in the amount of osteoid tissue and particularly immature woven bone. The animal experiments indicated that there are two mechanisms for this new bone formation. These different mechanisms may explain the different radiographic appearances. Irrespective of the mechanism of production, this new bone had a markedly increased avidity for bone-seeking isotopes. When the tumour was successfully irradiated the bone lost its osteoblastic reaction, and the production of immature new bone ceased as did the increased uptake of bone-seeking isotopes. Investigation of the vascularity of the lesion showed that there was an increase in small vessels in the neighbourhood of the tumour. The results of the study suggest that the uptake of isotope occurs in two phases. During the first phase, which occurs very rapidly, large amounts of isotope accumulate in the extracellular fluid following the increased vascularity. In the second slower phase, the isotope is gradually concentrated by the reactive immature new woven bone. (author)

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

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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.

The interrelation between aPKC and glucose uptake in the skeletal muscle during contraction and insulin stimulation.

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Santos, J M; Benite-Ribeiro, S A; Queiroz, G; Duarte, J A

2014-12-01

Contraction and insulin increase glucose uptake in skeletal muscle. While the insulin pathway, better characterized, requires activation of phosphoinositide 3-kinase (PI3K) and atypical protein kinase (aPKC), muscle contraction seems to share insulin-activated components to increase glucose uptake. This study aimed to investigate the interrelation between the pathway involved in glucose uptake evoked by insulin and muscle contraction. Isolated muscle of rats was treated with solvent (control), insulin, wortmannin (PI3K inhibitor) and the combination of insulin plus wortmannin. After treatment, muscles were electrically stimulated (contracted) or remained at rest. Glucose transporter 4 (GLUT4) localization, glucose uptake and phospho-aPKC (aPKC activated form) were assessed. Muscle contraction and insulin increased glucose uptake in all conditions when compared with controls not stimulating an effect that was accompanied by an increase in GLUT4 and of phospho-aPKC at the muscle membrane. Contracted muscles treated with insulin did not show additive effects on glucose uptake or aPKC activity compared with the response when these stimuli were applied alone. Inhibition of PI3K blocked insulin effect on glucose uptake and aPKC but not in the contractile response. Thus, muscle contraction seems to stimulate aPKC and glucose uptake independently of PI3K. Therefore, aPKC may be a convergence point and a rate limit step in the pathway by which, insulin and contraction, increase glucose uptake in skeletal muscle. Copyright © 2014 John Wiley & Sons, Ltd.

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

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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...

Effect of exercise and obesity on skeletal muscle amino acid uptake

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Friedman, J.E.

1988-01-01

To determine if amino acid uptake by muscle of the obese Zucker rat is impaired, epitrochlearis (EPI) and soleus strip (SOL) muscles from 32 pairs of female lean (Fa/-) and obese (fa/fa) Zucker rats were incubated using [ 14 C]α-aminoisobutyric acid (AIB). Because contractile activity also influences amino acid uptake, the effect of acute endurance exercise on amino acid uptake by skeletal muscle from lean and obese rats was also studied. Muscle wet and dry weights were similar in lean and obese rats. However, both muscle protein content and concentration from obese rats were significantly reduced. In preliminary studies, pinning EPI at resting length during incubation significantly increased AIB uptake and reduced muscle water accumulation. AIB uptake was similar in stripped and intact SOL. Lean and obese rats were studied at rest or following a 1 hr treadmill run at 8% grade Muscles were pinned, and preincubated for 30 min at 37 degree C in Krebs Ringer bicarbonate buffer (KRB) containing 5mM glucose under 95:5 O 2 /CO 2 , followed by 30, 60, 120, or 180 min of incubation in KRB with 0.5 mM AIB, [ 14 C]-AIB to measure amino acid, and [ 3 H]-inulin to determine extracellular water

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

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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...

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

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Sylow, Lykke; Møller, Lisbeth L V; Kleinert, Maximilian; Richter, Erik A; Jensen, Thomas E

2014-12-01

Muscle contraction stimulates muscle glucose uptake by facilitating translocation of glucose transporter 4 from intracellular locations to the cell surface, which allows for diffusion of glucose into the myofibres. The intracellular mechanisms regulating this process are not well understood. The GTPase Rac1 has, until recently, been investigated only with regard to its involvement in insulin-stimulated glucose uptake. However, we recently found that Rac1 is activated during muscle contraction and exercise in mice and humans. Remarkably, Rac1 seems to be necessary for exercise and contraction-stimulated glucose uptake in skeletal muscle, because muscle-specific Rac1 knockout mice display reduced ex vivo contraction- and in vivo exercise-stimulated glucose uptake. The molecular mechanism by which Rac1 regulates glucose uptake is presently unknown. However, recent studies link Rac1 to the actin cytoskeleton, the small GTPase RalA and/or free radical production, which have previously been shown to be regulators of glucose uptake in muscle. We propose a model in which Rac1 is activated by contraction- and exercise-induced mechanical stress signals and that Rac1 in conjunction with other signalling regulates glucose uptake during muscle contraction and exercise. © 2014 The Authors. Experimental Physiology © 2014 The Physiological Society.

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

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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.

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

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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)

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

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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.

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

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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.

Bone turnover markers are correlated with total skeletal uptake of 99mTc-methylene diphosphonate (99mTc-MDP)

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Lenora, Janaka; Norrgren, Kristina; Thorsson, Ola; Wollmer, Per; Obrant, Karl J; Ivaska, Kaisa K

2009-01-01

Skeletal uptake of 99m Tc labelled methylene diphosphonate ( 99m Tc-MDP) is used for producing images of pathological bone uptake due to its incorporation to the sites of active bone turnover. This study was done to validate bone turnover markers using total skeletal uptake (TSU) of 99m Tc-MDP. 22 postmenopausal women (52–80 years) volunteered to participate. Scintigraphy was performed by injecting 520 MBq of 99m Tc-MDP and taking whole body images after 3 minutes, and 5 hours. TSU was calculated from these two images by taking into account the urinary loss and soft tissue uptake. Bone turnover markers used were bone specific alkaline phosphatase (S-Bone ALP), three different assays for serum osteocalcin (OC), tartrate resistant acid phosphatase 5b (S-TRACP5b), serum C-terminal cross-linked telopeptides of type I collagen (S-CTX-I) and three assays for urinary osteocalcin (U-OC). The median TSU of 99m Tc-MDP was 23% of the administered activity. All bone turnover markers were significantly correlated with TSU with r-values from 0.52 (p = 0.013) to 0.90 (p < 0.001). The two resorption markers had numerically higher correlations (S-TRACP5b r = 0.90, S-CTX-I r = 0.80) than the formation markers (S-Total OC r = 0.72, S-Bone ALP r = 0.66), but the difference was not statistically significant. TSU did not correlate with age, weight, body mass index or bone mineral density. In conclusion, bone turnover markers are strongly correlated with total skeletal uptake of 99m Tc-MDP. There were no significant differences in correlations for bone formation and resorption markers. This should be due to the coupling between formation and resorption

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.

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

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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.

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

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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...

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...

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

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

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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.

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

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

DEFF Research Database (Denmark)

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...

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)

Glucose uptake patterns in exercised skeletal muscles of elite male long-distance and short-distance runners.

Science.gov (United States)

Tai, Suh-Jun; Liu, Ren-Shyan; Kuo, Ya-Chen; Hsu, Chi-Yang; Chen, Chi-Hsien

2010-04-30

The aim of this study was to determine glucose uptake patterns in exercised skeletal muscles of elite male long-distance and short-distance runners. Positron emission tomography (PET) using 18F-fluoro-2-deoxyglucose (FDG) was performed to determine the patterns of glucose uptake in lower limbs of short-distance (SD group, n=8) and long-distance (LD group, n=8) male runners after a modified 20 min Bruce treadmill test. Magnetic resonance imaging (MRI) was used to delineate the muscle groups in lower limbs. Muscle groups from hip, knee, and ankle movers were measured. The total FDG uptake and the standard uptake value (SUV) for each muscle group were compared between the 2 groups. For the SD and LD runners, the 2 major muscle groups utilizing glucose during running were knee extensors and ankle plantarflexors, which accounted for 49.3 +/- 8.1% (25.1 +/- 4.7% and 24.2 +/- 6.0%) of overall lower extremity glucose uptake for SD group, and 51.3 +/- 8.0% (27.2 +/- 2.7% and 24.0 +/- 8.1%) for LD group. No difference in muscle glucose uptake was noted for other muscle groups. For SD runners, the SUVs for the muscle groups varied from 0.49 +/- 0.27 for the ankle plantarflexors, to 0.20 +/- 0.08 for the hip flexor. For the LD runners, the highest and lowest SUVs were 0.43 +/- 0.15 for the ankle dorsiflexors and 0.21 +/- 0.19 for the hip. For SD and LD groups, no difference in muscle SUV was noted for the muscle groups. However, the SUV ratio between the ankle dorsiflexors and plantarflexors in the LD group was significantly greater than that in the SD group. We thus conclude that the major propelling muscle groups account for approximately 50% of lower limb glucose utilization during running. Thus, the other muscle groups involving maintenance of balance, limb deceleration, and shock absorption utilize an equal amount. This result provides a new insight into glucose distribution in skeletal muscle, suggesting that propellers and supporters are both energetically important

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

DEFF Research Database (Denmark)

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...

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

International Nuclear Information System (INIS)

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

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...

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

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

An atlas of normal skeletal scintigraphy

International Nuclear Information System (INIS)

Flanagan, J.J.; Maisey, M.N.

1985-01-01

This atlas was compiled to provide the neophyte as well as the experienced radiologist and the nuclear medicine physician with a reference on normal skeletal scintigraphy as an aid in distinguishing normal variations in skeletal uptake from abnormal findings. Each skeletal scintigraph is labeled, and utilizing an identical scale, a relevant skeletal photograph and radiograph are placed adjacent to the scintigraph

Assessment of mandibular growth by skeletal scintigraphy

International Nuclear Information System (INIS)

Kaban, L.B.; Cisneros, G.J.; Heyman, S.; Treves, S.

1982-01-01

Accurate assessment of facial skeletal growth remains a major problem in craniomaxillofacial surgery. Current methods include: (1) comparisons of chronologic age with growth histories of the patient and the family, (2) hand-wrist radiographs compared with a standard, and (3) serial cephalometric radiographs. Uptake of technetium-99m methylene diphosphonate into bone is a reflection of current metabolic activity and blood flow. Therefore, scintigraphy with this radiopharmaceutical might serve as a good method of assessing skeletal growth. Thirty-four patients, ranging in age from 15 months to 22 years, who were undergoing skeletal scintigrams for acute pathologic conditions of the extremities, were used to develop standards of uptake based on age and skeletal maturation. The results indicate that skeletal scintigraphy may be useful in evaluation of mandibular growth

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.

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...

Nitrogen and Phosphorus Plant Uptake During Periods with no Photosynthesis Accounts for About Half of Global Annual Uptake

Science.gov (United States)

Riley, W. J.; Zhu, Q.; Tang, J.

2017-12-01

Uncertainties in current Earth System Model (ESM) predictions of terrestrial carbon-climate feedbacks over the 21st century are as large as, or larger than, any other reported natural system uncertainties. Soil Organic Matter (SOM) decomposition and photosynthesis, the dominant fluxes in this regard, are tightly linked through nutrient availability, and the recent Coupled Model Inter-comparison Project 5 (CMIP5) used for climate change assessment had no credible representations of these constraints. In response, many ESM land models (ESMLMs) have developed dynamic and coupled soil and plant nutrient cycles. Here we quantify terrestrial carbon cycle impacts from well-known observed plant nutrient uptake mechanisms ignored in most current ESMLMs. In particular, we estimate the global role of plant root nutrient competition with microbes and abiotic process at night and during the non-growing season using the ACME land model (ALMv1-ECA-CNP) that explicitly represents these dynamics. We first demonstrate that short-term nutrient uptake dynamics and competition between plants and microbes are accurately predicted by the model compared to 15N and 33P isotopic tracer measurements from more than 20 sites. We then show that global nighttime and non-growing season nitrogen and phosphorus uptake accounts for 46 and 45%, respectively, of annual uptake, with large latitudinal variation. Model experiments show that ignoring these plant uptake periods leads to large positive biases in annual N leaching (globally 58%) and N2O emissions (globally 68%). Biases these large will affect modeled carbon cycle dynamics over time, and lead to predictions of ecosystems that have overly open nutrient cycles and therefore lower capacity to sequester carbon.

The Global Influence of Cloud Optical Thickness on Terrestrial Carbon Uptake

Science.gov (United States)

Zhu, P.; Cheng, S. J.; Keppel-Aleks, G.; Butterfield, Z.; Steiner, A. L.

2016-12-01

Clouds play a critical role in regulating Earth's climate. One important way is by changing the type and intensity of solar radiation reaching the Earth's surface, which impacts plant photosynthesis. Specifically, the presence of clouds modifies photosynthesis rates by influencing the amount of diffuse radiation as well as the spectral distribution of solar radiation. Satellite-derived cloud optical thickness (COT) may provide the observational constraint necessary to assess the role of clouds on ecosystems and terrestrial carbon uptake across the globe. Previous studies using ground-based observations at individual sites suggest that below a COT of 7, there is a greater increase in light use efficiency than at higher COT values, providing evidence for higher carbon uptake rates than expected given the reduction in radiation by clouds. However, the strength of the COT-terrestrial carbon uptake correlation across the globe remains unknown. In this study, we investigate the influence of COT on terrestrial carbon uptake on a global scale, which may provide insights into cloud conditions favorable for plant photosynthesis and improve our estimates of the land carbon sink. Global satellite-derived MODIS data show that tropical and subtropical regions tend to have COT values around or below the threshold during growing seasons. We find weak correlations between COT and GPP with Fluxnet MTE global GPP data, which may be due to the uncertainty of upscaling GPP from individual site measurements. Analysis with solar-induced fluorescence (SIF) as a proxy for GPP is also evaluated. Overall, this work constructs a global picture of the role of COT on terrestrial carbon uptake, including its temporal and spatial variations.

Skeletal imaging composition

International Nuclear Information System (INIS)

Vanduzee, B.F.; Degenhardt, C.R.

1983-01-01

This invention is based on the discovery that the adjustment of pH, within a particular range, during the process of manufacturing lyophilized diphosphonate-containing skeletal imaging kits yields a kit which produces a technetium skeletal imaging agent with superior imaging properties. This increased performance is manifested through faster blood clearance and higher skeletal uptake of the technetium imaging agent. The process for producing a dry-powder imaging kit comprises the steps of: preparing a solution of a diphosphonate carrier, stannous reductant, and a stabilizer in water; adjusting the pH to between 5.5 and 6.5; and lyophilizing the solution

Lyophilized skeletal imaging composition

International Nuclear Information System (INIS)

Vanduzee, B.F.

1983-01-01

This invention encompasses a process for producing a dry-powder skeletal imaging kit. An aqueous solution of a diphosphonate, a stannous reductant, and, optionally, a stabilizer is prepared. The solution is adjusted to a pH within the range 4.2 to 4.8 and the pH-adjusted solution is then lyophilized. The adjustment of pH, within a particular range, during the process of manufacturing lyophilized diphosphonate containing skeletal imaging kits yields a kit which produces a technetium skeletal imaging agent with superior imaging properties. This improved performance is manifested through faster blood clearance and higher skeletal uptake of the technetium imaging agent

Involvement of Rac1 and the actin cytoskeleton in insulin- and contraction-stimulated intracellular signaling and glucose uptake in mature skeletal muscle

DEFF Research Database (Denmark)

Sylow, Lykke

understood. The aim of the current PhD was therefore to investigate the involvement of Rac1 and the actin cytoskeleton in the regulation of insulin- and contraction-stimulated glucose uptake in mature skeletal muscle. The central findings of this PhD thesis was that Rac1 was activated by both insulin...

Skeletal scintigraphic changes in osteoporosis treated with sodium fluoride: concise communication

International Nuclear Information System (INIS)

Schulz, E.E.; Libanati, C.R.; Farley, S.M.; Kirk, G.A.; Baylink, D.J.

1984-01-01

An appendicular skeletal response to sodium fluoride (NaF) was detected by total skeletal scintigrams. Twelve postmenopausal osteoporotic women were treated with NaF (88 mg/day) and calcium (1500 mg/day). Total skeletal scintigrams were obtained before and during treatment. Within 4 to 21 mo (mean: 8.3), all 12 patients showed new areas of increased uptake corresponding to metaphyseal regions and short bones of the appendicular skeleton. Nine patients showed an increase in serum alkaline phosphatase activity, which was attributed to an increase in the skeletal isoenzyme. Seven of 12 patients developed bone pain in one or more of the regions of increased uptake. This study establishes that the skeletal scintigram is a sensitive index of the peripheral skeletal response to NaF

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

Science.gov (United States)

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.

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

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

Increased bone radiotracer uptake in renal osteodystrophy

Energy Technology Data Exchange (ETDEWEB)

de Graaf, P.; Schicht, I.M.; de Graeff, J.; te Velde, J.; Kleiverda, K.; Pauwels, E.K.J.

1982-04-01

Bone radiotracer uptake in renal osteodystrophy was investigated in 35 dialysis patients by correlating the results of quantitative bone scintigraphy with those of biochemical and bone morphometric studies. There were highly significant correlations (P < 0.001) between the total skeletal activity and the biochemical (iPTH and alkaline phosphatase), and histologic parameters of hyperparathyroidism. These clinical results strongly suggest that increased bone turnover i.e. hyperparathyroidism, rather than osteomalacia is the major cause of increased skeletal uptake in renal osteodystrophy.

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

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

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.)

The Impact of Endurance Training on Human Skeletal Muscle Memory, Global Isoform Expression and Novel Transcripts.

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Maléne E Lindholm

2016-09-01

Full Text Available Regularly performed endurance training has many beneficial effects on health and skeletal muscle function, and can be used to prevent and treat common diseases e.g. cardiovascular disease, type II diabetes and obesity. The molecular adaptation mechanisms regulating these effects are incompletely understood. To date, global transcriptome changes in skeletal muscles have been studied at the gene level only. Therefore, global isoform expression changes following exercise training in humans are unknown. Also, the effects of repeated interventions on transcriptional memory or training response have not been studied before. In this study, 23 individuals trained one leg for three months. Nine months later, 12 of the same subjects trained both legs in a second training period. Skeletal muscle biopsies were obtained from both legs before and after both training periods. RNA sequencing analysis of all 119 skeletal muscle biopsies showed that training altered the expression of 3,404 gene isoforms, mainly associated with oxidative ATP production. Fifty-four genes had isoforms that changed in opposite directions. Training altered expression of 34 novel transcripts, all with protein-coding potential. After nine months of detraining, no training-induced transcriptome differences were detected between the previously trained and untrained legs. Although there were several differences in the physiological and transcriptional responses to repeated training, no coherent evidence of an endurance training induced transcriptional skeletal muscle memory was found. This human lifestyle intervention induced differential expression of thousands of isoforms and several transcripts from unannotated regions of the genome. It is likely that the observed isoform expression changes reflect adaptational mechanisms and processes that provide the functional and health benefits of regular physical activity.

Skeletal muscle glucose uptake during dynamic exercise in humans

DEFF Research Database (Denmark)

Richter, Erik; Kiens, Bente; Saltin, Bengt

1988-01-01

uptake was not compensated for by increased uptake of free fatty acids but was accompanied by decreases in plasma insulin and increases in plasma epinephrine and norepinephrine. During work with large muscle masses, arterial lactate increased to approximately 6 mM, and net leg lactate release reverted......To study the role of muscle mass in glucoregulation, six subjects worked with the knee extensors of one leg on a specially constructed cycle ergometer. The knee extensors of one leg worked either alone or in combination with the knee extensors of the other leg and/or with the arms. Substrate usage...... to net lactate uptake. Decreased glucose uptake could not be explained by decreased perfusion. It is concluded that thigh muscle glucose uptake is affected by the size of the total muscle mass engaged in exercise. The decrease in thigh glucose uptake, when arm cranking was added and O2 uptake...

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...

Decreased bone uptake of technetium-99m polyphosphate in thalassemia major

International Nuclear Information System (INIS)

Valdez, V.A.; Jacobstein, J.G.

1980-01-01

Bone scans were performed with Tc-99m stannous polyphosphate on four patients with thalassemia major. Three of the scans show generalized decrease in skeletal uptake of the radiopharmaceutical, associated with renal enlargement and markedly increased renal radioactivity. The skeletal findings are consistent with the known bone abnormalities in thalassemia major, which are secondary to the extensive marrow hyperplasia and include loss of trabeculae and cortical thinning with consequent loss of bone mass. The increased renal uptake is probably due in part to the increased renal excretion (secondary to the poor bone uptake) and in part to the tubular dilatation and renal enlargement associated with thalassemia major. In addition, the presence of excessive amounts of iron in these patients may play a role in both the skeletal and renal findings

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...

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

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.

Global ocean carbon uptake: magnitude, variability and trends

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R. Wanninkhof

2013-03-01

Full Text Available The globally integrated sea–air anthropogenic carbon dioxide (CO2 flux from 1990 to 2009 is determined from models and data-based approaches as part of the Regional Carbon Cycle Assessment and Processes (RECCAP project. Numerical methods include ocean inverse models, atmospheric inverse models, and ocean general circulation models with parameterized biogeochemistry (OBGCMs. The median value of different approaches shows good agreement in average uptake. The best estimate of anthropogenic CO2 uptake for the time period based on a compilation of approaches is −2.0 Pg C yr−1. The interannual variability in the sea–air flux is largely driven by large-scale climate re-organizations and is estimated at 0.2 Pg C yr−1 for the two decades with some systematic differences between approaches. The largest differences between approaches are seen in the decadal trends. The trends range from −0.13 (Pg C yr−1 decade−1 to −0.50 (Pg C yr−1 decade−1 for the two decades under investigation. The OBGCMs and the data-based sea–air CO2 flux estimates show appreciably smaller decadal trends than estimates based on changes in carbon inventory suggesting that methods capable of resolving shorter timescales are showing a slowing of the rate of ocean CO2 uptake. RECCAP model outputs for five decades show similar differences in trends between approaches.

Audit of the global carbon budget: estimate errors and their impact on uptake uncertainty

Science.gov (United States)

Ballantyne, A. P.; Andres, R.; Houghton, R.; Stocker, B. D.; Wanninkhof, R.; Anderegg, W.; Cooper, L. A.; DeGrandpre, M.; Tans, P. P.; Miller, J. B.; Alden, C.; White, J. W. C.

2015-04-01

Over the last 5 decades monitoring systems have been developed to detect changes in the accumulation of carbon (C) in the atmosphere and ocean; however, our ability to detect changes in the behavior of the global C cycle is still hindered by measurement and estimate errors. Here we present a rigorous and flexible framework for assessing the temporal and spatial components of estimate errors and their impact on uncertainty in net C uptake by the biosphere. We present a novel approach for incorporating temporally correlated random error into the error structure of emission estimates. Based on this approach, we conclude that the 2σ uncertainties of the atmospheric growth rate have decreased from 1.2 Pg C yr-1 in the 1960s to 0.3 Pg C yr-1 in the 2000s due to an expansion of the atmospheric observation network. The 2σ uncertainties in fossil fuel emissions have increased from 0.3 Pg C yr-1 in the 1960s to almost 1.0 Pg C yr-1 during the 2000s due to differences in national reporting errors and differences in energy inventories. Lastly, while land use emissions have remained fairly constant, their errors still remain high and thus their global C uptake uncertainty is not trivial. Currently, the absolute errors in fossil fuel emissions rival the total emissions from land use, highlighting the extent to which fossil fuels dominate the global C budget. Because errors in the atmospheric growth rate have decreased faster than errors in total emissions have increased, a ~20% reduction in the overall uncertainty of net C global uptake has occurred. Given all the major sources of error in the global C budget that we could identify, we are 93% confident that terrestrial C uptake has increased and 97% confident that ocean C uptake has increased over the last 5 decades. Thus, it is clear that arguably one of the most vital ecosystem services currently provided by the biosphere is the continued removal of approximately half of atmospheric CO2 emissions from the atmosphere

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...

Global pathway analysis using DNA microarrays in skeletal muscle of women with polycystic ovary syndrome

DEFF Research Database (Denmark)

Skov, Vibe

2007-01-01

(study 1), to investigate whether pioglitazone therapy could reverse abnormalities in the transcriptional profile of muscle associated with insulin resistance in skeletal muscle of obese PCOS patients (study 2), and to develop a microarray platform for global gene expression profiling (study 3). In study...... comparable to other commercial and custom made microarrays and is a cost-effective alternative especially in larger epidemiological studies....

A compact skeletal mechanism for n -dodecane with optimized semi-global low-temperature chemistry for diesel engine simulations

Energy Technology Data Exchange (ETDEWEB)

Yao, Tong; Pei, Yuanjiang; Zhong, Bei-Jing; Som, Sibendu; Lu, Tianfeng; Luo, Kai Hong

2017-03-01

A skeletal mechanism with 54 species and 269 reactions was developed to predict pyrolysis and oxidation of n-dodecane as a diesel fuel surrogate involving both high-temperature (high-T) and low-temperature (low-T) conditions. The skeletal mechanism was developed from a semi-detailed mechanism developed at the University of Southern California (USC). Species and reactions for high-T pyrolysis and oxidation of C5-C12 were reduced by using reaction flow analysis (RFA), isomer lumping, and then merged into a skeletal C0-C4 core to form a high-T sub-mechanism. Species and lumped semi-global reactions for low-T chemistry were then added to the high-T sub-mechanism and a 54-species skeletal mechanism is obtained. The rate parameters of the low-T reactions were tuned against a detailed mechanism by the Lawrence Livermore National Laboratory (LLNL), as well as the Spray A flame experimental data, to improve the prediction of ignition delay at low-T conditions, while the high-T chemistry remained unchanged. The skeletal mechanism was validated for auto-ignition, perfectly stirred reactors (PSR), flow reactors and laminar premixed flames over a wide range of flame conditions. The skeletal mechanism was then employed to simulate three-dimensional turbulent spray flames at compression ignition engine conditions and validated against experimental data from the Engine Combustion Network (ECN).

Diffuse hepatic and splenic 99mTc MPD tracer uptake in case of multiple myeloma

International Nuclear Information System (INIS)

Sood, Ashwani; Seam, Rajeev Kumar; Sethi, Sandeep; Gupta, Manish

2010-01-01

99m Tc-methylene diphosphonate (MDP) bone scintigraphy has long been used for the evaluation of benign as well as malignant skeletal conditions. However, non-osseous tracer uptake on a bone scan is an unusual finding. There is a need to understand the pathophysiological basis of the non-osseous uptake, which may have a clinical relevance or deteriorating effect on the quality of the bone scan. We describe a case of multiple myeloma, where extraosseous uptake in the form of diffuse hepatic and splenic uptake, with almost normal skeletal tracer distribution, has been seen on the bone scan. (author)

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....

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.

Extraosseous radiotracer uptake on bone scan in beta-thalassemia: report of one case

International Nuclear Information System (INIS)

Guezguez, M.; Nouira, M.; Sfar, R.; Chatti, K.; Ben Fradj, M.; Ben Ali, K.; Ajmi, S.; Essabbah, H.; Zrour, S.

2009-01-01

Red blood cell transfusion, main therapeutic modality of beta-thalassemia, leads to iron overload which may perturb several metabolic ways. The aim of this paper is to illustrate the uptake abnormalities observed on bone scan of thalassaemic patients and to discuss mechanisms of extraosseous accumulation of the radiopharmaceutical in this pathology. We report a 16-year-old child suffering from beta-thalassemia major undergoing transfusion therapy. A bone scan was indicated to look for osseous infection. This study revealed a little skeletal uptake and abnormal liver, splenic and renal accumulation. A repeat bone scan, performed three weeks later showed a better skeletal uptake which enabled the discovery of focal abnormalities and made the diagnostic easier. The effect of iron overload on radiopharmaceuticals uptake in bone scan is known since 1975. Dissociation of 99m Tc from the carrier ligand due to the presence of iron excess seems the most plausible hypothesis. Free 99m Tc can be bound to other tissular substrates which can explain extraosseous uptake. The normally available pool for bone is reduced and then the skeletal uptake decreased. This report limits considerably the sensitivity of the bone scan. A well-led iron chelation and eventually the use of diuretic drug may guarantee a better quality of bone scan images. (authors)

[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.

Skeletal muscle insulin resistance associated with cholesterol-induced activation of macrophages is prevented by high density lipoprotein.

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Andrew L Carey

Full Text Available BACKGROUND: Emerging evidence suggests that high density lipoprotein (HDL may modulate glucose metabolism through multiple mechanisms including pancreatic insulin secretion as well as insulin-independent glucose uptake into muscle. We hypothesized that HDL may also increase skeletal muscle insulin sensitivity via cholesterol removal and anti-inflammatory actions in macrophages associated with excess adiposity and ectopic lipid deposition. METHODS: Human primary and THP-1 macrophages were treated with vehicle (PBS or acetylated low density lipoprotein (acLDL with or without HDL for 18 hours. Treatments were then removed, and macrophages were incubated with fresh media for 4 hours. This conditioned media was then applied to primary human skeletal myotubes derived from vastus lateralis biopsies taken from patients with type 2 diabetes to examine insulin-stimulated glucose uptake. RESULTS: Conditioned media from acLDL-treated primary and THP-1 macrophages reduced insulin-stimulated glucose uptake in primary human skeletal myotubes compared with vehicle (primary macrophages, 168±21% of basal uptake to 104±19%; THP-1 macrophages, 142±8% of basal uptake to 108±6%; P<0.05. This was restored by co-treatment of macrophages with HDL. While acLDL increased total intracellular cholesterol content, phosphorylation of c-jun N-terminal kinase and secretion of pro- and anti-inflammatory cytokines from macrophages, none were altered by co-incubation with HDL. Insulin-stimulated Akt phosphorylation in human skeletal myotubes exposed to conditioned media was unaltered by either treatment condition. CONCLUSION: Inhibition of insulin-stimulated glucose uptake in primary human skeletal myotubes by conditioned media from macrophages pre-incubated with acLDL was restored by co-treatment with HDL. However, these actions were not linked to modulation of common pro- or anti-inflammatory mediators or insulin signaling via Akt.

Peripheral endocannabinoids regulate skeletal muscle development and maintenance

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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.

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

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.)

Skeletal and reticuloendothelial imaging in osteopetrosis: case report

International Nuclear Information System (INIS)

Park, H.M.; Lambertus, J.

1977-01-01

Skeletal and reticuloendothelial images, using Tc-99m HEDP and Tc-99m sulfur colloid, respectively, were obtained from two adult patients with osteopetrosis. Skeletal images demonstrated increased activity in multiple fracture sites, in mandibular osteomyelitis, in ends of splayed long bones adjacent to joints, and in the epiphyseal ends of short tubular bones. The remainder of the skeleton involved with osteopetrosis showed no generalized increased uptake of Tc-99m HEDP. These findings indicate that metabolic activity in this disease is abnormally increased in the usual areas of bone growth but appears normal elsewhere. Reticuloendothelial imaging showed an almost total lack of activity in the axial and peripheral skeletal marrow space. Anemia, however, was only moderate in these patients. Skeletal scintigraphy may be useful to evaluate the presence and extent of the frequent complications of osteopetrosis, namely fractures and osteomyelitis

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...

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....

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

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

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...

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

DEFF Research Database (Denmark)

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 ...

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.

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.

Osteopoikilosis: A Sign Mimicking Skeletal Metastases in a Cancer Patient

Directory of Open Access Journals (Sweden)

Hamid Nasrolahi

2011-01-01

Full Text Available Osteopoikilosis is a rare benign osteosclerotic bone disorder that may be misdiagnosed as skeletal metastases. Here we describe a case of coincidental breast cancer and osteopoikilosis mimicking skeletal metastases. A 41-year-old woman underwent right modified radical mastectomy in April 2007. Twenty-eight months after initial treatment,the patient complained of bilateral knee and foot pain. Plain X-rays of the feet and knees showed multiple well-defined osteosclerotic lesions. According to the radiographic appearance, the most likely differential diagnoses included skeletal metastases from breast cancer and osteopoikilosis. A whole-body bone scintigraphy showed no increase in uptake by the sclerotic lesions, and serum lactic dehydrogenase, carcinoembryonic antigen, alkaline phosphatase and cancer antigen 15-3 were not elevated. We therefore diagnosed the patient’s skeletal lesions as osteopoikilosis. This case and ourliterature review suggest that the radiographic appearance of osteopoikilosis may mimic or mask skeletal metastases, potentially leading to misdiagnosis in patients with cancer.

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

Skeletal metastases from hepatoma: frequency, distribution, and radiographic features

International Nuclear Information System (INIS)

Kuhlman, J.E.; Fishman, E.K.; Leichner, P.K.; Magid, D.; Order, S.E.; Siegelman, S.S.

1986-01-01

Over the past 6 years, the authors evaluated 300 patients with hepatoma as part of phase 1 and 2 treatment protocol trials. Analysis of the available clinical data and radiographic studies revealed 22 patients (7.3%) with skeletal metastases demonstrated by radiography, computed tomography (CT), and/or nuclear scintigraphy. The plain film appearance of skeletal metastases from hepatoma was osteolytic in all cases. CT scanning best demonstrated the expansile, destructive nature of these metastases, which were often associated with large, bulky soft-tissue masses. Skeletal metastases from hepatomas demonstrated increased radiotracer uptake on standard bone scans and were gallium avid, similar to the hepatoma itself. In addition, they could be targeted therapeutically with I-131 antiferritin immunoglobulin. The most frequent sites of skeletal metastases were the ribs, spine, femur, pelvis, and humerus. An initial symptom in ten patients was skeletal pain corresponding to the osseous metastases. In five patients, pathologic fractures of the proximal femur or humerus developed and required total hip replacement or open-reduction internal fixation. Patients with long-standing cirrhosis or known hepatocellular carcinoma who also have skeletal symptoms should be evaluated for possible osseous metastases

Skeletal unloading induces selective resistance to the anabolic actions of growth hormone on bone

Science.gov (United States)

Halloran, B. P.; Bikle, D. D.; Harris, J.; Autry, C. P.; Currier, P. A.; Tanner, S.; Patterson-Buckendahl, P.; Morey-Holton, E.

1995-01-01

Loss of skeletal weight bearing or physical unloading of bone in the growing animal inhibits bone formation and induces a bone mineral deficit. To determine whether the inhibition of bone formation induced by skeletal unloading in the growing animal is a consequence of diminished sensitivity to growth hormone (GH) we studied the effects of skeletal unloading in young hypophysectomized rats treated with GH (0, 50, 500 micrograms/100 g body weight/day). Skeletal unloading reduced serum osteocalcin, impaired uptake of 3H-proline into bone, decreased proximal tibial mass, and diminished periosteal bone formation at the tibiofibular junction. When compared with animals receiving excipient alone, GH administration increased bone mass in all animals. The responses in serum osteocalcin, uptake of 3H-proline and 45Ca into the proximal tibia, and proximal tibial mass in non-weight bearing animals were equal to those in weight bearing animals. The responses in trabecular bone volume in the proximal tibia and bone formation at the tibiofibular junction to GH, however, were reduced significantly by skeletal unloading. Bone unloading prevented completely the increase in metaphyseal trabecular bone normally induced by GH and severely dampened the stimulatory effect (158% vs. 313%, p anabolic actions of GH.

Increased muscle glucose uptake after exercise

DEFF Research Database (Denmark)

Richter, Erik; Ploug, Thorkil; Galbo, Henrik

1985-01-01

responsiveness of glucose uptake was noted only in controls. Analysis of intracellular glucose-6-phosphate, glucose, glycogen synthesis, and glucose transport suggested that the exercise effect on responsiveness might be due to enhancement of glucose disposal. After electrical stimulation of diabetic...... of glucose. At maximal insulin concentrations, the enhancing effect of exercise on glucose uptake may involve enhancement of glucose disposal, an effect that is probably less in muscle from diabetic rats.(ABSTRACT TRUNCATED AT 250 WORDS)......It has recently been shown that insulin sensitivity of skeletal muscle glucose uptake and glycogen synthesis is increased after a single exercise session. The present study was designed to determine whether insulin is necessary during exercise for development of these changes found after exercise...

Lung uptake in bone scan - Two case reports

International Nuclear Information System (INIS)

Nahar, N.; Kabir, F.; Islam, N.; Karim, M.A.

2001-01-01

Breast cancer is the 2nd most common cancer in female in our country. When a case of breast cancer is diagnosed a base line bone scan is asked for to exclude skeletal metastasis. This helps for treatment planning and future follow up. Scan pattern in bone metastasis is usually multiple, randomly distributed foci of intensely increased tracer accumulation. Uptake of radio pharmaceutical in breast tissue is frequently observed. Kidneys are another extra skeletal organs through which 99m Tc-MDP is excreted and that's why normal kidneys are faintly visualized in delayed views suggesting normal exertion of tracer. If there is any outflow obstruction in any kidney, it will show hold up of radiotracer on that side. Often radiopharmaceuticals are seen to accumulate in other organs like lungs. Here two cases of breast cancer are discussed where bone scan shows significant uptake of tracer in lungs

Role of mesoscale eddies in the global ocean uptake of anthropogenic CO2

International Nuclear Information System (INIS)

Zouhair, Lachkar

2007-02-01

Mesoscale eddies play a fundamental role in ocean dynamics particularly in the Southern Ocean. Global-scale tracer simulations are typically made at coarse resolution without explicitly modeling eddies. Here we ask what role do eddies play in ocean uptake, storage, and meridional transport of anthropogenic CO 2 , CFC-11 and bomb Δ 14 C. We made global anthropogenic transient tracer simulations in coarse-resolution, ORCA2, and eddy-permitting, ORCA05 and ORCA025, versions of the ocean modelling system NEMO. We focus on the Southern Ocean where tracer air-sea fluxes are largest. Eddies have little effect on bomb Δ 14 C uptake and storage. Yet for CFC-11 and anthropogenic CO 2 , increased eddy activity reduces southern extra-tropical uptake by 28% and 25% respectively, thereby providing better agreement with observations. It is shown that the discrepancies in the equilibration times between the three tracers determine their respective sensitivities to the model horizontal resolution. Applying Gent and McWilliams (1990) (GM) parameterization of eddies in the non-eddying version of the model does improve results, but not enough. An in-depth investigation of the mechanisms by which eddies affect the uptake of the transient tracers shows that including mesoscale eddies leads to an overall reduction in the Antarctic Intermediate Water (AAIW) ventilation, and modifies substantially the spatial distribution of their source regions. This investigation reveals also that the GM parameterization still overestimates the ventilation and the subduction of AAIW in the Indian Ocean where the simulated mixed layer is particularly deep during the winter. This work suggests that most current coarse-resolution models may overestimate the ventilation of AAIW in the Indian sector of the Southern Ocean. This study shows also that the use of the GM parameterization may be of limited utility where mixed layer is relatively deep and confirms the general need for a more adequate

Extra-osseous uterine pathophysiology demonstrated on skeletal scintigraphy

International Nuclear Information System (INIS)

Mansberg, R.; Lewis, G.

1999-01-01

Full text: Skeletal scintigraphy is a sensitive procedure for evaluating disease and trauma involving the skeleton. Extra-skeletal pathophysiology is also often demonstrated. This may include uptake by tumours, soft tissue calcification and infection as well as renal pathology. Skeletal scintigraphy is often performed to evaluate hip and back pain and extra-osseous uterine pathophysiology can be demonstrated in both the early and late phases of the study as in the following cases. Three women underwent skeletal scintigraphy for the investigation of low back pain in two patients and post-partum hip pain in one. A large vascular uterus with deviation of the bladder was demonstrated in the post-partum patient. Increased pelvic vascularity and bladder deviation in the second patient was shown by ultrasound to correspond to a left-sided fibroid with associated adenomyosis. In the third case, right-sided pelvic vascularity and left bladder deviation were shown on ultrasound to be due to an anteverted, anteflexed uterus tilted to the right. These cases illustrate the importance of documenting extra-osseous findings on skeletal scintigraphy and the benefits of correlation with anatomical imaging

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

DEFF Research Database (Denmark)

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...

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.

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

Skeletal unloading induces selective resistance to the anabolic actions of growth hormone on bone

Science.gov (United States)

Halloran, B. P.; Bikle, D. D.; Harris, J.; Autry, C. P.; Currier, P. A.; Tanner, S.; Patterson-Buckendahl, P.; Morey-Holton, E.

1995-01-01

Loss of skeletal weight bearing or physical unloading of bone in the growing animal inhibits bone formation and induces a bone mineral deficit. To determine whether the inhibition of bone formation induced by skeletal unloading in the growing animal is a consequence of diminished sensitivity to growth hormone (GH) we studied the effects of skeletal unloading in young hypophysectomized rats treated with GH (0, 50, 500 micrograms/100 g body weight/day). Skeletal unloading reduced serum osteocalcin, impaired uptake of 3H-proline into bone, decreased proximal tibial mass, and diminished periosteal bone formation at the tibiofibular junction. When compared with animals receiving excipient alone, GH administration increased bone mass in all animals. The responses in serum osteocalcin, uptake of 3H-proline and 45Ca into the proximal tibia, and proximal tibial mass in non-weight bearing animals were equal to those in weight bearing animals. The responses in trabecular bone volume in the proximal tibia and bone formation at the tibiofibular junction to GH, however, were reduced significantly by skeletal unloading. Bone unloading prevented completely the increase in metaphyseal trabecular bone normally induced by GH and severely dampened the stimulatory effect (158% vs. 313%, p < 0.002) of GH on periosteal bone formation. These results suggest that while GH can stimulate the overall accumulation of bone mineral in both weight bearing and non-weight bearing animals, skeletal unloading selectively impairs the response of trabecular bone and periosteal bone formation to the anabolic actions of GH.

Skeletal unloading induces selective resistance to the anabolic actions of growth hormone on bone

Science.gov (United States)

Halloran, B. P.; Bikle, D. D.; Harris, J.; Autry, C. P.; Currier, P. A.; Tanner, S.; Patterson-Buckendahl, P.; Morey-Holton, E.

1995-01-01

Loss of skeletal weight bearing or physical unloading of bone in the growing animal inhibits bone formation and induces a bone mineral deficit. To determine whether the inhibition of bone formation induced by skeletal unloading in the growing animal is a consequence of diminished sensitivity to growth hormone (GH) we studied the effects of skeletal unloading in young hypophysectomized rats treated with GH (0, 50, 500 micrograms/100 g body weight/day). Skeletal unloading reduced serum osteocalcin, impaired uptake of 3H-proline into bone, decreased proximal tibial mass, and diminished periosteal bone formation at the tibiofibular junction. When compared with animals receiving excipient alone, GH administration increased bone mass in all animals. The responses in serum osteocalcin, uptake of 3H-proline and 45Ca into the proximal tibia, and proximal tibial mass in non-weight bearing animals were equal to those in weight bearing animals. The responses in trabecular bone volume in the proximal tibia and bone formation at the tibiofibular junction to GH, however, were reduced significantly by skeletal unloading. Bone unloading prevented completely the increase in metaphyseal trabecular bone normally induced by GH and severely dampened the stimulatory effect (158% vs. 313%, p bone formation. These results suggest that while GH can stimulate the overall accumulation of bone mineral in both weight bearing and non-weight bearing animals, skeletal unloading selectively impairs the response of trabecular bone and periosteal bone formation to the anabolic actions of GH.

A physiological skeletal model for radionuclide and stable element biokinetics in children and adults

International Nuclear Information System (INIS)

Richardson, R.B.

2010-01-01

A physiological skeletal model (PSM) is described that represents the skeletal uptake, retention and clearance of both bone-surface-seeking and bone-volume-seeking radionuclides and stable elements. A key objective of the PSM is to model the higher skeletal growth and bone turnover in infants and children (compared to adults) in order to to account for their greater uptake and cancer risk from bone-seeking contaminants such as lead and plutonium. The PSM is a compartmental model that allows for the incorporation of organic and inorganic material in the bone volume via quiescent bone surfaces, forming bone surfaces and the lacuno-canaliculi system. The model uniquely incorporates a tertiary phase of mineralization via bone fluids. The PSM's structural concepts and biokinetic parameters - such as realistic mass transfers, organ and tissue masses, and bone remodelling half times - are selected mainly on the basis of physiological and anatomical criteria. For brevity, model parameter values or evaluated for adults only. The PSM is an improvement on existing skeletal models that are based more on compartment structures and pathways that rendered good fits to biokinetic data rather than on being anatomically and physiologically accurate. (author)

FDG-PET response of skeletal (bone marrow and bone) involvement after induction chemotherapy in pediatric Hodgkin lymphoma - Are specific response criteria required?

Science.gov (United States)

Georgi, Thomas Walter; Kluge, Regine; Kurch, Lars; Chavdarova, Lidia; Hasenclever, Dirk; Stoevesandt, Dietrich; Pelz, Tanja; Landman-Parker, Judith; Wallace, Hamish; Karlen, Jonas; Fernandez-Teijeiro, Ana; Cepelova, Michaela; Fossa, Alexander; Balwierz, Walentyna; Attarbaschi, Andishe; Ammann, Roland A; Pears, Jane; Hraskova, Andrea; Uyttebroeck, Anne; Beishuizen, Auke; Dieckmann, Karin; Leblanc, Thierry; Daw, Stephen; Baumann, Julia; Körholz, Dieter; Sabri, Osama; Mauz-Körholz, Christine

2018-04-13

Purpose: This study focused on skeletal involvement in FDG-PET (PET) in Hodgkin lymphoma (HL). We aimed at a systematic evaluation of the different types of skeletal involvement and their PET response after two cycles of chemotherapy (PET-2), to answer the question whether the current PET response criterion for skeletal involvement is suitable. A secondary objective was to observe the influence of initial uptake intensity and metabolic tumor volume (MTV) of skeletal lesions on the PET-2 response. Methods: Initial PET scans (PET-0) of 1068 pediatric HL patients from the EuroNet-PHL-C1 (C1) trial were evaluated by central review for skeletal involvement. Three types of skeletal lesions were distinguished: skeletal lesions detected only in PET (PETonly), bone marrow (BM) lesions confirmed by MRI or BM biopsy and bone lesions. Uptake intensity (measured as qPET value) and MTV were calculated for each skeletal lesion. All PET-2 scans were assessed for residual tumor activity. The rates of complete metabolic response in PET-2 of skeletal and nodal involvement were compared. Results: 139/1068 (13%) C1 patients showed skeletal involvement (44/139 PETonly patients, 32/139 BM patients and 63/139 bone patients). 101/139 (73%) patients became PET-2 negative in the skeleton while lymph node involvement was PET-2 negative in 94/139 (68%) patients. Highest skeletal PET-2 negative rate was seen in 42/44 (95%) PETonly patients, followed by 22/32 (69%) BM patients and 37/63 (59%) bone patients. Skeletal lesions who became PET-2 negative showed lower median values for initial qPET (2.74) and MTV (2ml) than lesions who remained PET-2 positive (3.84; 7ml). Conclusion: In this study with pediatric HL patients, the complete response rate in PET-2 of skeletal and nodal involvement was similar. Bone flare seemed to be irrelevant. Overall, the current skeletal PET response criterion - comparison with the local skeletal background - is well suited. Initial uptake intensity and MTV of

Skeletal metastases from primary hepatocellular carcinoma

International Nuclear Information System (INIS)

Kim, So Sun; Huh, Jin Do; Kim, Ho Joon; Chun, Byung Hee; Joh, Young Duk; Chang, Hee Kyung; Huh, Man Ha

1988-01-01

In order to detect and to evaluate the frequency, the distribution, and the radiological findings of skeletal metastases from hepatocellular carcinoma, the authors retrospectively analyzed radiographic, scintigraphic, and CT findings of 257 patients with hepatocellular carcinoma. The results were as follows: 1. Skeletal metastases were demonstrated in 21 patients (8.2%). 2. Frequent symptoms were pain, limitation of motion, paralysis, and mass. In nine of them the initial symptoms were due to skeletal metastases. 3. The common sites of metastases were spine (13 cases), ribs (8 cases), pelvis (8 cases) and femur (6 cases). Humerus, skull and sternum were also frequently involved. 4. Plain film findings were purely osteolytic in all cases and pathologic fractures were noted in 5 cases. 5. The lesions appear expansible in 7 cases, and 4 of them showed associated soft tissue masses on CT scans. 6. Bone scans were performed in 13 cases of them and showed increased radiotracer uptake in all. 7. Angiographic studies of 3 cases showed hypervascularity of the metastatic lesions as well as the primary hepatic tumor.

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

DEFF Research Database (Denmark)

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...

A mechanistic, globally-applicable model of plant nitrogen uptake, retranslocation and fixation

Science.gov (United States)

Fisher, J. B.; Tan, S.; Malhi, Y.; Fisher, R. A.; Sitch, S.; Huntingford, C.

2008-12-01

Nitrogen is one of the nutrients that can most limit plant growth, and nitrogen availability may be a controlling factor on biosphere responses to climate change. We developed a plant nitrogen assimilation model based on a) advective transport through the transpiration stream, b) retranslocation whereby carbon is expended to resorb nitrogen from leaves, c) active uptake whereby carbon is expended to acquire soil nitrogen, and d) biological nitrogen fixation whereby carbon is expended for symbiotic nitrogen fixers. The model relies on 9 inputs: 1) net primary productivity (NPP), 2) plant C:N ratio, 3) available soil nitrogen, 4) root biomass, 5) transpiration rate, 6) saturated soil depth,7) leaf nitrogen before senescence, 8) soil temperature, and 9) ability to fix nitrogen. A carbon cost of retranslocation is estimated based on leaf nitrogen and compared to an active uptake carbon cost based on root biomass and available soil nitrogen; for nitrogen fixers both costs are compared to a carbon cost of fixation dependent on soil temperature. The NPP is then allocated to optimize growth while maintaining the C:N ratio. The model outputs are total plant nitrogen uptake, remaining NPP available for growth, carbon respired to the soil and updated available soil nitrogen content. We test and validate the model (called FUN: Fixation and Uptake of Nitrogen) against data from the UK, Germany and Peru, and run the model under simplified scenarios of primary succession and climate change. FUN is suitable for incorporation into a land surface scheme of a General Circulation Model and will be coupled with a soil model and dynamic global vegetation model as part of a land surface model (JULES).

Muscle contraction increases carnitine uptake via translocation of OCTN2

Energy Technology Data Exchange (ETDEWEB)

Furuichi, Yasuro [Graduate School of Natural Science and Technology, Kanazawa University, Kanazawa (Japan); Sugiura, Tomoko; Kato, Yukio [Faculty of Pharmacy, Kanazawa University, Kanazawa (Japan); Takakura, Hisashi [Faculty of Human Sciences, Kanazawa University, Kanazawa (Japan); Hanai, Yoshiteru [Nagoya Institute of Technology, Nagoya (Japan); Hashimoto, Takeshi [Ritsumeikan University, Kusatsu (Japan); Masuda, Kazumi, E-mail: masuda@ed.kanazawa-u.ac.jp [Faculty of Human Sciences, Kanazawa University, Kanazawa (Japan)

2012-02-24

Highlights: Black-Right-Pointing-Pointer Muscle contraction augmented carnitine uptake into rat hindlimb muscles. Black-Right-Pointing-Pointer An increase in carnitine uptake was due to an intrinsic clearance, not blood flow. Black-Right-Pointing-Pointer Histochemical analysis showed sarcolemmal OCTN2 was emphasized after contraction. Black-Right-Pointing-Pointer OCTN2 protein in sarcolemmal fraction was increased in contracting muscles. -- Abstract: Since carnitine plays an important role in fat oxidation, influx of carnitine could be crucial for muscle metabolism. OCTN2 (SLC22A5), a sodium-dependent solute carrier, is assumed to transport carnitine into skeletal muscle cells. Acute regulation of OCTN2 activity in rat hindlimb muscles was investigated in response to electrically induced contractile activity. The tissue uptake clearance (CL{sub uptake}) of L-[{sup 3}H]carnitine during muscle contraction was examined in vivo using integration plot analysis. The CL{sub uptake} of [{sup 14}C]iodoantipyrine (IAP) was also determined as an index of tissue blood flow. To test the hypothesis that increased carnitine uptake involves the translocation of OCTN2, contraction-induced alteration in the subcellular localization of OCTN2 was examined. The CL{sub uptake} of L-[{sup 3}H]carnitine in the contracting muscles increased 1.4-1.7-fold as compared to that in the contralateral resting muscles (p < 0.05). The CL{sub uptake} of [{sup 14}C]IAP was much higher than that of L-[{sup 3}H]carnitine, but no association between the increase in carnitine uptake and blood flow was obtained. Co-immunostaining of OCTN2 and dystrophin (a muscle plasma membrane marker) showed an increase in OCTN2 signal in the plasma membrane after muscle contraction. Western blotting showed that the level of sarcolemmal OCTN2 was greater in contracting muscles than in resting muscles (p < 0.05). The present study showed that muscle contraction facilitated carnitine uptake in skeletal muscles, possibly

Muscle contraction increases carnitine uptake via translocation of OCTN2

International Nuclear Information System (INIS)

Furuichi, Yasuro; Sugiura, Tomoko; Kato, Yukio; Takakura, Hisashi; Hanai, Yoshiteru; Hashimoto, Takeshi; Masuda, Kazumi

2012-01-01

Highlights: ► Muscle contraction augmented carnitine uptake into rat hindlimb muscles. ► An increase in carnitine uptake was due to an intrinsic clearance, not blood flow. ► Histochemical analysis showed sarcolemmal OCTN2 was emphasized after contraction. ► OCTN2 protein in sarcolemmal fraction was increased in contracting muscles. -- Abstract: Since carnitine plays an important role in fat oxidation, influx of carnitine could be crucial for muscle metabolism. OCTN2 (SLC22A5), a sodium-dependent solute carrier, is assumed to transport carnitine into skeletal muscle cells. Acute regulation of OCTN2 activity in rat hindlimb muscles was investigated in response to electrically induced contractile activity. The tissue uptake clearance (CL uptake ) of L-[ 3 H]carnitine during muscle contraction was examined in vivo using integration plot analysis. The CL uptake of [ 14 C]iodoantipyrine (IAP) was also determined as an index of tissue blood flow. To test the hypothesis that increased carnitine uptake involves the translocation of OCTN2, contraction-induced alteration in the subcellular localization of OCTN2 was examined. The CL uptake of L-[ 3 H]carnitine in the contracting muscles increased 1.4–1.7-fold as compared to that in the contralateral resting muscles (p uptake of [ 14 C]IAP was much higher than that of L-[ 3 H]carnitine, but no association between the increase in carnitine uptake and blood flow was obtained. Co-immunostaining of OCTN2 and dystrophin (a muscle plasma membrane marker) showed an increase in OCTN2 signal in the plasma membrane after muscle contraction. Western blotting showed that the level of sarcolemmal OCTN2 was greater in contracting muscles than in resting muscles (p < 0.05). The present study showed that muscle contraction facilitated carnitine uptake in skeletal muscles, possibly via the contraction-induced translocation of its specific transporter OCTN2 to the plasma membrane.

Early growth response-1 negative feedback regulates skeletal muscle postprandial insulin sensitivity via activating Ptp1b transcription.

Science.gov (United States)

Wu, Jing; Tao, Wei-Wei; Chong, Dan-Yang; Lai, Shan-Shan; Wang, Chuang; Liu, Qi; Zhang, Tong-Yu; Xue, Bin; Li, Chao-Jun

2018-03-15

Postprandial insulin desensitization plays a critical role in maintaining whole-body glucose homeostasis by avoiding the excessive absorption of blood glucose; however, the detailed mechanisms that underlie how the major player, skeletal muscle, desensitizes insulin action remain to be elucidated. Herein, we report that early growth response gene-1 ( Egr-1) is activated by insulin in skeletal muscle and provides feedback inhibition that regulates insulin sensitivity after a meal. The inhibition of the transcriptional activity of Egr-1 enhanced the phosphorylation of the insulin receptor (InsR) and Akt, thus increasing glucose uptake in L6 myotubes after insulin stimulation, whereas overexpression of Egr-1 decreased insulin sensitivity. Furthermore, deletion of Egr-1 in the skeletal muscle improved systemic insulin sensitivity and glucose tolerance, which resulted in lower blood glucose levels after refeeding. Mechanistic analysis demonstrated that EGR-1 inhibited InsR phosphorylation and glucose uptake in skeletal muscle by binding to the proximal promoter region of protein tyrosine phosphatase-1B (PTP1B) and directly activating transcription. PTP1B knockdown largely restored insulin sensitivity and enhanced glucose uptake, even under conditions of EGR-1 overexpression. Our results indicate that EGR-1/PTP1B signaling negatively regulates postprandial insulin sensitivity and suggest a potential therapeutic target for the prevention and treatment of excessive glucose absorption.-Wu, J., Tao, W.-W., Chong, D.-Y., Lai, S.-S., Wang, C., Liu, Q., Zhang, T.-Y., Xue, B., Li, C.-J. Early growth response-1 negative feedback regulates skeletal muscle postprandial insulin sensitivity via activating Ptp1b transcription.

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.

Skeletal scintigraphy and quantitative tracer studies in metabolic bone disease

Science.gov (United States)

Fogelman, Ignac

Bone scan imaging with the current bone seeking radiopharmaceuticals, the technetium-99m labelled diphosphonates, has dramatically improved our ability to evaluate skeletal pathology. In this thesis, chapter 1 presents a review of the history of bone scanning, summarises present concepts as to the mechanism of uptake of bone seeking agents and briefly illustrates the role of bone scanning in clinical practice. In chapter 2 the applications of bone scan imaging and quantitative tracer techniques derived from the bone scan in the detection of metabolic bone disease are discussed. Since skeletal uptake of Tc-99m diphosphonate depends upon skeletal metabolism one might expect that the bone scan would be of considerable value in the assessment of metabolic bone disease. However in these disorders the whole skeleton is often diffusely involved by the metabolic process and simple visual inspection of the scan image may not reveal the uniformly increased uptake of tracer. Certain patterns of bone scan abnormality have, however, been reported in patients with primary hyperparathyroidism and renal osteo-dystrophy; the present studies extend these observations and introduce the concept of "metabolic features" which are often recognisable in conditions with generalised increased bone turnover. As an aid to systematic recognition of these features on a given bone scan image a semi-quantitative scoring system, the metabolic index, was introduced. The metabolic index allowed differentiation between various groups of patients with metabolic disorders and a control population. In addition, in a bone scan study of patients with acromegaly, it was found that the metabolic index correlated well with disease activity as measured by serum growth hormone levels. The metabolic index was, however, found to be a relatively insensitive means of identifying disease in individual patients. Patients with increased bone turnover will have an absolute increase in skeletal uptake of tracer. As a

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

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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.

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...

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.

Polyunsaturated fatty acids acutely affect triacylglycerol-derived skeletal muscle fatty acid uptake and increases postprandial insulin sensitivity

NARCIS (Netherlands)

Jans, Anneke; Konings, Ellen; Goossens, Gijs H.; Bouwman, Freek G.; Moors, Chantalle C.; Boekschoten, Mark; Afman, Lydia; Muller, Michael; Mariman, Edwin C.; Blaak, Ellen E.

2012-01-01

Dietary fat quality may influence skeletal muscle lipid handling and fat accumulation, thereby modulating insulin sensitivity. Objective: To examine acute effects of meals with various fatty acid (FA) compositions on skeletal muscle FA handling and postprandial insulin sensitivity in obese insulin

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...

Human skeletal uptake of natural alpha radioactivity from 210Pb-supported 210Po

International Nuclear Information System (INIS)

Oyedepo, A.C.

1998-06-01

This thesis contributes to increasing knowledge on the dosimetry of natural alpha-particle radiation in skeletal tissues, particularly in utero, and associated risks of malignancy. Alpha-particle radiation is an established aetiological factor of cancer. In the human body, polonium-210 decayed from skeletal lead-210 ( 210 Pb/ 210 Po) is the predominant natural alpha-emitter. 210 Pb displaces calcium (Ca) in mineral hydroxyapatite, especially during periods of rapid bone growth and remodelling when Ca is laid down. It was therefore necessary to study alpha activity uptake and calcification concurrently within bone. Human studies were undertaken on: fetal vertebrae, 17 - 42 weeks of gestation, 74 samples; adult vertebrae, 40 - 95 years, 40 samples; and adult ribs, 20 - 95 years, 51 samples. Specimens were unconcentrated and weighed 210 Pb/ 210 Po. Alpha track data were resolved by specially written software named SPATS (Selection Program for Analysing Track Structures). Ca and phosphorus (P) were biochemically determined. Results were examined for trends in bone type, gender and chronological ageing in humans. The main research findings were: 1) The Ca content of fetal vertebrae increased linearly at a weekly rate of 0.2g Ca 100 g -1 wet bone (typical values of 2, 4, 6 g 100 g -1 at 16, 26 and 36 weeks). 2) The P concentration also increased with advancing fetal age. 3) The Ca:P bone weight ratio rose from 1.7 to 2.2 by 32 gestational weeks. 4) The overall range in bone 210 Pb/ 210 Po alpha activity was 0.25 - 1.1 Bq kg -1 with correlation between activity concentration and fetal age (0.47 ± 0.05 Bq kg -1 for 17 - 26 weeks, 0.67 ± 0.04 Bq kg -1 for 32 - 42 weeks). 5) The correlation between increased alpha radioactivity and increased Ca concentration approximating to 0.0046 Bq g -1 of Ca. 6) A decreasing Ca content of adult vertebrae with increasing age from 40 - 95 years, from ∼ 14 to 5 g 100 g-1, but no correlation with age for adult rib Ca content of 10 - 30 g

Tribbles 3 Mediates Endoplasmic Reticulum Stress-Induced Insulin Resistance in Skeletal Muscle

Science.gov (United States)

Koh, Ho-Jin; Toyoda, Taro; Didesch, Michelle M.; Lee, Min-Young; Sleeman, Mark W.; Kulkarni, Rohit N.; Musi, Nicolas; Hirshman, Michael F.; Goodyear, Laurie J.

2013-01-01

Endoplasmic Reticulum (ER) stress has been linked to insulin resistance in multiple tissues but the role of ER stress in skeletal muscle has not been explored. ER stress has also been reported to increase tribbles 3 (TRB3) expression in multiple cell lines. Here, we report that high fat feeding in mice, and obesity and type 2 diabetes in humans significantly increases TRB3 and ER stress markers in skeletal muscle. Overexpression of TRB3 in C2C12 myotubes and mouse tibialis anterior muscles significantly impairs insulin signaling. Incubation of C2C12 cells and mouse skeletal muscle with ER stressors thapsigargin and tunicamycin increases TRB3 and impairs insulin signaling and glucose uptake, effects reversed in cells overexpressing RNAi for TRB3 and in muscles from TRB3 knockout mice. Furthermore, TRB3 knockout mice are protected from high fat diet-induced insulin resistance in skeletal muscle. These data demonstrate that TRB3 mediates ER stress-induced insulin resistance in skeletal muscle. PMID:23695665

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

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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.

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....

Endothelial Fcγ Receptor IIB Activation Blunts Insulin Delivery to Skeletal Muscle to Cause Insulin Resistance in Mice

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Tanigaki, Keiji; Chambliss, Ken L.; Yuhanna, Ivan S.; Sacharidou, Anastasia; Ahmed, Mohamed; Atochin, Dmitriy N.; Huang, Paul L.

2016-01-01

Modest elevations in C-reactive protein (CRP) are associated with type 2 diabetes. We previously revealed in mice that increased CRP causes insulin resistance and mice globally deficient in the CRP receptor Fcγ receptor IIB (FcγRIIB) were protected from the disorder. FcγRIIB is expressed in numerous cell types including endothelium and B lymphocytes. Here we investigated how endothelial FcγRIIB influences glucose homeostasis, using mice with elevated CRP expressing or lacking endothelial FcγRIIB. Whereas increased CRP caused insulin resistance in mice expressing endothelial FcγRIIB, mice deficient in the endothelial receptor were protected. The insulin resistance with endothelial FcγRIIB activation was due to impaired skeletal muscle glucose uptake caused by attenuated insulin delivery, and it was associated with blunted endothelial nitric oxide synthase (eNOS) activation in skeletal muscle. In culture, CRP suppressed endothelial cell insulin transcytosis via FcγRIIB activation and eNOS antagonism. Furthermore, in knock-in mice harboring constitutively active eNOS, elevated CRP did not invoke insulin resistance. Collectively these findings reveal that by inhibiting eNOS, endothelial FcγRIIB activation by CRP blunts insulin delivery to skeletal muscle to cause insulin resistance. Thus, a series of mechanisms in endothelium that impairs insulin movement has been identified that may contribute to type 2 diabetes pathogenesis. PMID:27207525

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 ...

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

Soil Methanotrophy Model (MeMo v1.0): a process-based model to quantify global uptake of atmospheric methane by soil

Science.gov (United States)

Murguia-Flores, Fabiola; Arndt, Sandra; Ganesan, Anita L.; Murray-Tortarolo, Guillermo; Hornibrook, Edward R. C.

2018-06-01

Soil bacteria known as methanotrophs are the sole biological sink for atmospheric methane (CH4), a potent greenhouse gas that is responsible for ˜ 20 % of the human-driven increase in radiative forcing since pre-industrial times. Soil methanotrophy is controlled by a plethora of factors, including temperature, soil texture, moisture and nitrogen content, resulting in spatially and temporally heterogeneous rates of soil methanotrophy. As a consequence, the exact magnitude of the global soil sink, as well as its temporal and spatial variability, remains poorly constrained. We developed a process-based model (Methanotrophy Model; MeMo v1.0) to simulate and quantify the uptake of atmospheric CH4 by soils at the global scale. MeMo builds on previous models by Ridgwell et al. (1999) and Curry (2007) by introducing several advances, including (1) a general analytical solution of the one-dimensional diffusion-reaction equation in porous media, (2) a refined representation of nitrogen inhibition on soil methanotrophy, (3) updated factors governing the influence of soil moisture and temperature on CH4 oxidation rates and (4) the ability to evaluate the impact of autochthonous soil CH4 sources on uptake of atmospheric CH4. We show that the improved structural and parametric representation of key drivers of soil methanotrophy in MeMo results in a better fit to observational data. A global simulation of soil methanotrophy for the period 1990-2009 using MeMo yielded an average annual sink of 33.5 ± 0.6 Tg CH4 yr-1. Warm and semi-arid regions (tropical deciduous forest and open shrubland) had the highest CH4 uptake rates of 602 and 518 mg CH4 m-2 yr-1, respectively. In these regions, favourable annual soil moisture content ( ˜ 20 % saturation) and low seasonal temperature variations (variations < ˜ 6 °C) provided optimal conditions for soil methanotrophy and soil-atmosphere gas exchange. In contrast to previous model analyses, but in agreement with recent observational data

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 Hansen, Andreas; Andersen, Nynne Bjerre; 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...

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

DEFF Research Database (Denmark)

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...

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...

Regulatory mechanisms of skeletal muscle protein turnover during exercise

DEFF Research Database (Denmark)

Rose, Adam John; Richter, Erik

2009-01-01

Skeletal muscle protein turnover is a relatively slow metabolic process that is altered by various physiological stimuli such as feeding/fasting and exercise. During exercise, catabolism of amino acids contributes very little to ATP turnover in working muscle. With regards to protein turnover......, there is now consistent data from tracer studies in rodents and humans showing that global protein synthesis is blunted in working skeletal muscle. Whether there is altered skeletal muscle protein breakdown during exercise remains unclear. The blunting of protein synthesis is believed to be mediated...... downstream of changes in intracellular Ca(2+) and energy turnover. In particular, a signaling cascade involving Ca(2+)-calmodulin-eEF2 kinase-eEF2 is implicated. The possible functional significance of altered protein turnover in working skeletal muscle during exercise is discussed. Further work...

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

Diagnostic performance of a computer-assisted diagnosis system for bone scintigraphy of newly developed skeletal metastasis in prostate cancer patients: search for low-sensitivity subgroups.

Science.gov (United States)

Koizumi, Mitsuru; Motegi, Kazuki; Koyama, Masamichi; Terauchi, Takashi; Yuasa, Takeshi; Yonese, Junji

2017-08-01

The computer-assisted diagnostic system for bone scintigraphy (BS) BONENAVI is used to evaluate skeletal metastasis. We investigated its diagnostic performance in prostate cancer patients with and without skeletal metastasis and searched for the problems. An artificial neural network (ANN) value was calculated in 226 prostate cancer patients (124 with skeletal metastasis and 101 without) using BS. Receiver operating characteristic curve analysis was performed and the sensitivity and specificity determined (cutoff ANN = 0.5). Patient's situation at the time of diagnosis of skeletal metastasis, computed tomography (CT) type, extent of disease (EOD), and BS uptake grade were analyzed. False-negative and false-positive results were recorded. BONENAVI showed 82% (102/124) of sensitivity and 83% (84/101) specificity for metastasis detection. There were no significant differences among CT types, although low EOD and faint BS uptake were associated with low ANN values and low sensitivity. Patients showed lower sensitivity during the follow-up period than staging work-up. False-negative lesions were often located in the pelvis or adjacent to it. They comprised not only solitary, faint BS lesions but also overlaying to urinary excretion. BONENAVI with BS has good sensitivity and specificity for detecting prostate cancer's osseous metastasis. Low EOD and faint BS uptake are associated with low sensitivity but not the CT type. Prostate cancer patients likely to have false-negative results during the follow-up period had a solitary lesion in the pelvis with faint BS uptake or lesions overlaying to urinary excretion.

Diffuse Pulmonary Uptake of Tc-99m Methylene Diphosphonate in a Patient with Non-tuberculosis Mycobacterial Infection

International Nuclear Information System (INIS)

Kwon, Hyun Woo; Chung, June Key; Lee, Dong Soo; Ab-Aziz, Aini

2010-01-01

Extra-osseous uptake of bone-seeking radiopharmaceuticals has been reported at various sites and it is known to be induced by various causes. Diffuse pulmonary infection, such as tuberculosis, can be a cause of lung uptake of bone-scan agent. Here we report on a patient with non-tuberculosis mycobacterial infection (NTM) who demonstrated diffuse pulmonary uptake on Tc-99m MDP bone scan. After medical treatment for NTM, the patient's lung lesions improved. Estra skeletal lung Tc-99m MDP uptake on bone scan may suggest lung parenchymal damage associated with disease activity.

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....

Glucocorticoids and inhibition of bone formation induced by skeletal unloading

International Nuclear Information System (INIS)

Halloran, B.P.; Bikle, D.D.; Cone, C.M.; Morey-Holton, E.

1988-01-01

Skeletal unloading or loss of normal weight bearing in the growing animal inhibits bone formation and reduces bone calcium. To determine whether the inhibition of bone formation induced by skeletal unloading is a consequence of an increase in plasma glucocorticoids and/or an increase in bone sensitivity to glucocorticoids, the authors measured plasma corticosterone throughout the day in unloaded and normally loaded rats (hindlimb elevation model) and examined the effect of adrenalectomy on the response of bone to skeletal unloading. Plasma corticosterone levels were similar in normally loaded and unloaded rats at all times. Skeletal unloading in sham-adrenalectomized animals reduced tibial and vertebral calcium by 11.5 and 11.1%, respectively, and in adrenalectomized animals by 15.3 and 20.3%, respectively. Uptake of 45 Ca and [ 3 H]proline in the tibia was reduced by 8 and 14%, respectively, in the sham-adrenalectomized animals and by 13 and 19% in the adrenalectomized animals. Bone formation and apposition rates were reduced to the same level in sham- and adrenalectomized animals. These results suggest that the inhibition of bone formation induced by skeletal unloading is not a consequence of increased plasma glucocorticoids or an increase in bone sensitivity to the glucocorticoids but, rather, point to a local mediator in bone that senses mechanical load and transmits that information to the bone-forming cells directly

Strong constraint on modelled global carbon uptake using solar-induced chlorophyll fluorescence data.

Science.gov (United States)

MacBean, Natasha; Maignan, Fabienne; Bacour, Cédric; Lewis, Philip; Peylin, Philippe; Guanter, Luis; Köhler, Philipp; Gómez-Dans, Jose; Disney, Mathias

2018-01-31

Accurate terrestrial biosphere model (TBM) simulations of gross carbon uptake (gross primary productivity - GPP) are essential for reliable future terrestrial carbon sink projections. However, uncertainties in TBM GPP estimates remain. Newly-available satellite-derived sun-induced chlorophyll fluorescence (SIF) data offer a promising direction for addressing this issue by constraining regional-to-global scale modelled GPP. Here, we use monthly 0.5° GOME-2 SIF data from 2007 to 2011 to optimise GPP parameters of the ORCHIDEE TBM. The optimisation reduces GPP magnitude across all vegetation types except C4 plants. Global mean annual GPP therefore decreases from 194 ± 57 PgCyr -1 to 166 ± 10 PgCyr -1 , bringing the model more in line with an up-scaled flux tower estimate of 133 PgCyr -1 . Strongest reductions in GPP are seen in boreal forests: the result is a shift in global GPP distribution, with a ~50% increase in the tropical to boreal productivity ratio. The optimisation resulted in a greater reduction in GPP than similar ORCHIDEE parameter optimisation studies using satellite-derived NDVI from MODIS and eddy covariance measurements of net CO 2 fluxes from the FLUXNET network. Our study shows that SIF data will be instrumental in constraining TBM GPP estimates, with a consequent improvement in global carbon cycle projections.

Samarium-153 EDTMP therapy of disseminated skeletal metastasis

International Nuclear Information System (INIS)

Turner, J.H.; Martindale, A.A.; Fleay, R.F.; Hoffman, R.F.; Claringbold, P.G.

1989-01-01

153 Sm-EDTMP (ethylenediaminetetramethylene phosphonate), prepared from a kit, was administered to 28 patients in a clinical trial of therapy for painful skeletal metastases unresponsive to all conventional treatment. The 103 keV gamma emission of 153 Sm was utilized for prospective individual estimation of beta radiation absorbed dose to red marrow to minimize myelotoxicity and provide optimum internal radiotherapy to skeletal metastases in each patient. Pain relief occurred within 14 days of administration of 153 Sm-EDTMP in 15 of 19 patients (79%) who could vie evaluated at 6 weeks, when clinical response was maximal. Duration of response ranged from 4 to 35 weeks. Recurrence of pain responded to retreatment with 153 Sm-EDTMP in five of eight cases. No dose-response relationship was apparent for pain relief but reversible myelotoxicity was frequently observed at radiation absorbed doses to bone marrow ≥270 cGy. Dosimetry calculation was based on pharmacokinetic studies of a tracer administration of 153 Sm-EDTMP in each patient. Assumptions inherent in this prospective method of predicting dose to bone marrow were validated experimentally. Biodistribution studies in rats demonstrated rapid skeletal uptake and long term retention of 153 Sm-EDTMP in bone over 5 days. Urinary clearance accounted for 40% of injected dose, and less than 0.5% of administered activity was retained in non osseous tissue. Microdensitometry of autoradiographs of sheep vertebra and femur confirmed surface uptake of 153 Sm-EDTMP in cortical bone and demonstrated relatively high trabecular bone activity which is the major component of radiation absorbed dose to bone marrow. Haematological studies in rabbits showed 153 Sm-EDTMP-induced myelotoxicity to be transient and no histopathological abnormalities were demonstrable with doses ten times greater than those administered to patients. (orig.)

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.

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.

Soil Methanotrophy Model (MeMo v1.0: a process-based model to quantify global uptake of atmospheric methane by soil

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F. Murguia-Flores

2018-06-01

Full Text Available Soil bacteria known as methanotrophs are the sole biological sink for atmospheric methane (CH4, a potent greenhouse gas that is responsible for  ∼  20 % of the human-driven increase in radiative forcing since pre-industrial times. Soil methanotrophy is controlled by a plethora of factors, including temperature, soil texture, moisture and nitrogen content, resulting in spatially and temporally heterogeneous rates of soil methanotrophy. As a consequence, the exact magnitude of the global soil sink, as well as its temporal and spatial variability, remains poorly constrained. We developed a process-based model (Methanotrophy Model; MeMo v1.0 to simulate and quantify the uptake of atmospheric CH4 by soils at the global scale. MeMo builds on previous models by Ridgwell et al. (1999 and Curry (2007 by introducing several advances, including (1 a general analytical solution of the one-dimensional diffusion–reaction equation in porous media, (2 a refined representation of nitrogen inhibition on soil methanotrophy, (3 updated factors governing the influence of soil moisture and temperature on CH4 oxidation rates and (4 the ability to evaluate the impact of autochthonous soil CH4 sources on uptake of atmospheric CH4. We show that the improved structural and parametric representation of key drivers of soil methanotrophy in MeMo results in a better fit to observational data. A global simulation of soil methanotrophy for the period 1990–2009 using MeMo yielded an average annual sink of 33.5 ± 0.6 Tg CH4 yr−1. Warm and semi-arid regions (tropical deciduous forest and open shrubland had the highest CH4 uptake rates of 602 and 518 mg CH4 m−2 yr−1, respectively. In these regions, favourable annual soil moisture content ( ∼  20 % saturation and low seasonal temperature variations (variations  <   ∼  6 °C provided optimal conditions for soil methanotrophy and soil–atmosphere gas exchange

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

Validation of a Novel Scoring System for Changes in Skeletal Manifestations of Hypophosphatasia in Newborns, Infants, and Children: The Radiographic Global Impression of Change Scale.

Science.gov (United States)

Whyte, Michael P; Fujita, Kenji P; Moseley, Scott; Thompson, David D; McAlister, William H

2018-05-01

Hypophosphatasia (HPP) is the heritable metabolic disease characterized by impaired skeletal mineralization due to low activity of the tissue-nonspecific isoenzyme of alkaline phosphatase. Although HPP during growth often manifests with distinctive radiographic skeletal features, no validated method was available to quantify them, including changes over time. We created the Radiographic Global Impression of Change (RGI-C) scale to assess changes in the skeletal burden of pediatric HPP. Site-specific pairs of radiographs of newborns, infants, and children with HPP from three clinical studies of asfotase alfa, an enzyme replacement therapy for HPP, were obtained at baseline and during treatment. Each pair was scored by three pediatric radiologists ("raters"), with nine raters across the three studies. Intrarater and interrater agreement was determined by weighted Kappa coefficients. Interrater reliability was assessed using intraclass correlation coefficients (ICCs) and by two-way random effects analysis of variance (ANOVA) and a mixed-model repeated measures ANOVA. Pearson correlation coefficients evaluated relationships of the RGI-C to the Rickets Severity Scale (RSS), Pediatric Outcomes Data Collection Instrument Global Function Parent Normative Score, Childhood Health Assessment Questionnaire Disability Index, 6-Minute Walk Test percent predicted, and Z-score for height in patients aged 6 to 12 years at baseline. Eighty-nine percent (8/9) of raters showed substantial or almost perfect intrarater agreement of sequential RGI-C scores (weighted Kappa coefficients, 0.72 to 0.93) and moderate or substantial interrater agreement (weighted Kappa coefficients, 0.53 to 0.71) in patients aged 0 to 12 years at baseline. Moderate-to-good interrater reliability was observed (ICC, 0.57 to 0.65). RGI-C scores were significantly (p ≤ 0.0065) correlated with the RSS and with measures of global function, disability, endurance, and growth in the patients aged 6 to 12 years at

Clinical application of skeletal scintigraphy and quantitative computed tomography (QCT) to osteoarthritis of the knee

International Nuclear Information System (INIS)

Mori, Muneshige

1989-01-01

Skeletal scintigraphy and QCT were performed to determine changes of subchondral bone tissues in osteoarthritis of the knee and findings were compared with plain X-ray findings, knee pain and femoro-tibial angle. Results on blood pool study were especially related to pain. Results in delayed study using single photon emission computed tomography revealed hign uptake on the medial side of the femur and tibia parallel to plain X-ray and pain. The QCT value was slightly decreased as osteoarthritic changes progressed without a significant change. In addition, delayed study in cases with previous surgical intervention by high tibial osteotomy revealed a lower uptake on the medial side of the femur and tibia. When skeletal scintigraphy accurately reflects blood flow through the subchondral bone tissues and is closely related to morbidity and pain, this modality is valuable in analysis of signs and symptoms as well as postoperative outcome. (author)

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

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...

AICAR administration affects glucose metabolism by upregulating the novel glucose transporter, GLUT8, in equine skeletal muscle.

Science.gov (United States)

de Laat, M A; Robinson, M A; Gruntmeir, K J; Liu, Y; Soma, L R; Lacombe, V A

2015-09-01

Equine metabolic syndrome is characterized by obesity and insulin resistance (IR). Currently, there is no effective pharmacological treatment for this insidious disease. Glucose uptake is mediated by a family of glucose transporters (GLUT), and is regulated by insulin-dependent and -independent pathways, including 5-AMP-activated protein kinase (AMPK). Importantly, the activation of AMPK, by 5-aminoimidazole-4-carboxamide-1-D-ribofuranoside (AICAR) stimulates glucose uptake in both healthy and diabetic humans. However, whether AICAR promotes glucose uptake in horses has not been established. It is hypothesized that AICAR administration would enhance glucose transport in equine skeletal muscle through AMPK activation. In this study, the effect of an intravenous AICAR infusion on blood glucose and insulin concentrations, as well as on GLUT expression and AMPK activation in equine skeletal muscle (quantified by Western blotting) was examined. Upon administration, plasma AICAR rapidly reached peak concentration. Treatment with AICAR resulted in a decrease (P change in lactate concentration. The ratio of phosphorylated to total AMPK was increased (P managing IR requires investigation. Copyright © 2015 Elsevier Ltd. All rights reserved.

Clinical significance of abnormal nonosseous soft tissue uptake of bone tracer

International Nuclear Information System (INIS)

Zhu Bao; Shang Yukun; Li Jiannan; Bai Jing; Cai Liang

2006-01-01

Objective: To evaluate the clinical significance of abnormal soft tissue uptake of bone tracer. Methods: Thirty patients with abnormal soft tissue uptake of bone tracer on 99 Tc m -methylene diphosphonic acid (MDP) skeletal imaging were analyzed. Radioactivity of soft tissue accumulated equal to or greater than the ribs were considered as abnormal. The result was compared with pathology, MRI, CT, X-ray, ultrasound, findings for evaluating its clinical significance. Results: In 7 patients with diffuse liver uptake of 99 Tc m -MDP, 6 were massive and 1 nodular liver cancer. In 2 patients with local liver uptake, one was metastatic and the other primary liver cancer. In 5 local lung uptake cases 4 were primary lung cancer and one metastatic. In 5 cases with colonic uptake 1 was schistosomiasis while the other 4 unexplainable. Subcutaneous tissue uptake was observed in 4 patients, symmetrical uptake in 2 patients with metastatic calcification microfoci in multiple myeloma, unsymmetrical uptake in 2 patients with hemangioma and abscess. Pleural uptake in 3 patients all was metastatic cancer. Abdominal uptake in 3 patients was omentum, paravertebral soft tissue metastasis and unknown cause. Breast uptake in one patient was due to breast cancer. Conclusions: There are many causes resulting in abnormal nonosseous soft tissue uptake of 99 Tc m -MDP. The final diagnosis should correlate with clinical data and other examinations. (authors)

Sonodelivery Facilitates Sustained Luciferase Expression from an Episomal Vector in Skeletal Muscle

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Manoel Figueiredo Neto

2015-07-01

Full Text Available Successful gene delivery to skeletal muscle is a desirable goal, not only for treating muscle diseases, but also for immunization, treatment of metabolic disorders, and/or delivering gene expression that can treat systemic conditions, such as bone metastatic cancer, for example. Although naked DNA uptake into skeletal muscle is possible, it is largely inefficient in the absence of additional chemical or physical delivery methods. We describe a system for delivery of non-viral or plasmid DNA to skeletal muscle using ultrasound-assisted sonoporation of a nanoplex combining plasmid DNA and a branched polymer based on poly(cyclooctene-graft-oligopeptide. The materials and methods described herein promise to advance the field of sonodelivery and of gene delivery to muscle for therapeutic applications since a simple system is presented that enables long-term gene expression in vivo with the promise of a minimal inflammatory gene expression profile.

Proteomic profiling of non-obese type 2 diabetic skeletal muscle

OpenAIRE

Mullen, Edel; Ohlendieck, Kay

2010-01-01

Abnormal glucose handling has emerged as a major clinical problem in millions of diabetic patients worldwide. Insulin resistance affects especially one of the main target organs of this hormone, the skeletal musculature, making impaired glucose metabolism in contractile fibres a major feature of type 2 diabetes. High levels of circulating free fatty acids, an increased intramyocellular lipid content, impaired insulin-mediated glucose uptake, diminished mitochondrial functioning and an overall...

Diffuse Pulmonary Uptake of Tc-99m Methylene Diphosphonate in a Patient with Non-tuberculosis Mycobacterial Infection

Energy Technology Data Exchange (ETDEWEB)

Kwon, Hyun Woo; Chung, June Key; Lee, Dong Soo [Seoul National University College of Medicine, Seoul (Korea, Republic of); Ab-Aziz, Aini [University Kebangsaan Malaysia Medical Centre, Kuala Lumpur, (Morocco)

2010-06-15

Extra-osseous uptake of bone-seeking radiopharmaceuticals has been reported at various sites and it is known to be induced by various causes. Diffuse pulmonary infection, such as tuberculosis, can be a cause of lung uptake of bone-scan agent. Here we report on a patient with non-tuberculosis mycobacterial infection (NTM) who demonstrated diffuse pulmonary uptake on Tc-99m MDP bone scan. After medical treatment for NTM, the patient's lung lesions improved. Estra skeletal lung Tc-99m MDP uptake on bone scan may suggest lung parenchymal damage associated with disease activity.

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...

Expanding the phenome and variome of skeletal dysplasia.

Science.gov (United States)

Maddirevula, Sateesh; Alsahli, Saud; Alhabeeb, Lamees; Patel, Nisha; Alzahrani, Fatema; Shamseldin, Hanan E; Anazi, Shams; Ewida, Nour; Alsaif, Hessa S; Mohamed, Jawahir Y; Alazami, Anas M; Ibrahim, Niema; Abdulwahab, Firdous; Hashem, Mais; Abouelhoda, Mohamed; Monies, Dorota; Al Tassan, Nada; Alshammari, Muneera; Alsagheir, Afaf; Seidahmed, Mohammed Zain; Sogati, Samira; Aglan, Mona S; Hamad, Muddathir H; Salih, Mustafa A; Hamed, Ahlam A; Alhashmi, Nadia; Nabil, Amira; Alfadli, Fatima; Abdel-Salam, Ghada M H; Alkuraya, Hisham; Peitee, Winnie Ong; Keng, W T; Qasem, Abdullah; Mushiba, Aziza M; Zaki, Maha S; Fassad, Mahmoud R; Alfadhel, Majid; Alexander, Saji; Sabr, Yasser; Temtamy, Samia; Ekbote, Alka V; Ismail, Samira; Hosny, Gamal Ahmed; Otaify, Ghada A; Amr, Khalda; Al Tala, Saeed; Khan, Arif O; Rizk, Tamer; Alaqeel, Aida; Alsiddiky, Abdulmonem; Singh, Ankur; Kapoor, Seema; Alhashem, Amal; Faqeih, Eissa; Shaheen, Ranad; Alkuraya, Fowzan S

2018-04-05

PurposeTo describe our experience with a large cohort (411 patients from 288 families) of various forms of skeletal dysplasia who were molecularly characterized.MethodsDetailed phenotyping and next-generation sequencing (panel and exome).ResultsOur analysis revealed 224 pathogenic/likely pathogenic variants (54 (24%) of which are novel) in 123 genes with established or tentative links to skeletal dysplasia. In addition, we propose 5 genes as candidate disease genes with suggestive biological links (WNT3A, SUCO, RIN1, DIP2C, and PAN2). Phenotypically, we note that our cohort spans 36 established phenotypic categories by the International Skeletal Dysplasia Nosology, as well as 18 novel skeletal dysplasia phenotypes that could not be classified under these categories, e.g., the novel C3orf17-related skeletal dysplasia. We also describe novel phenotypic aspects of well-known disease genes, e.g., PGAP3-related Toriello-Carey syndrome-like phenotype. We note a strong founder effect for many genes in our cohort, which allowed us to calculate a minimum disease burden for the autosomal recessive forms of skeletal dysplasia in our population (7.16E-04), which is much higher than the global average.ConclusionBy expanding the phenotypic, allelic, and locus heterogeneity of skeletal dysplasia in humans, we hope our study will improve the diagnostic rate of patients with these conditions.GENETICS in MEDICINE advance online publication, 5 April 2018; doi:10.1038/gim.2018.50.

Hydrogen improves glycemic control in type1 diabetic animal model by promoting glucose uptake into skeletal muscle.

Directory of Open Access Journals (Sweden)

Haruka Amitani

Full Text Available Hydrogen (H(2 acts as a therapeutic antioxidant. However, there are few reports on H(2 function in other capacities in diabetes mellitus (DM. Therefore, in this study, we investigated the role of H(2 in glucose transport by studying cultured mouse C2C12 cells and human hepatoma Hep-G2 cells in vitro, in addition to three types of diabetic mice [Streptozotocin (STZ-induced type 1 diabetic mice, high-fat diet-induced type 2 diabetic mice, and genetically diabetic db/db mice] in vivo. The results show that H(2 promoted 2-[(14C]-deoxy-d-glucose (2-DG uptake into C2C12 cells via the translocation of glucose transporter Glut4 through activation of phosphatidylinositol-3-OH kinase (PI3K, protein kinase C (PKC, and AMP-activated protein kinase (AMPK, although it did not stimulate the translocation of Glut2 in Hep G2 cells. H(2 significantly increased skeletal muscle membrane Glut4 expression and markedly improved glycemic control in STZ-induced type 1 diabetic mice after chronic intraperitoneal (i.p. and oral (p.o. administration. However, long-term p.o. administration of H(2 had least effect on the obese and non-insulin-dependent type 2 diabetes mouse models. Our study demonstrates that H(2 exerts metabolic effects similar to those of insulin and may be a novel therapeutic alternative to insulin in type 1 diabetes mellitus that can be administered orally.

Celastrol Protects against Antimycin A-Induced Insulin Resistance in Human Skeletal Muscle Cells

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Mohamad Hafizi Abu Bakar

2015-05-01

Full Text Available Mitochondrial dysfunction and inflammation are widely accepted as key hallmarks of obesity-induced skeletal muscle insulin resistance. The aim of the present study was to evaluate the functional roles of an anti-inflammatory compound, celastrol, in mitochondrial dysfunction and insulin resistance induced by antimycin A (AMA in human skeletal muscle cells. We found that celastrol treatment improved insulin-stimulated glucose uptake activity of AMA-treated cells, apparently via PI3K/Akt pathways, with significant enhancement of mitochondrial activities. Furthermore, celastrol prevented increased levels of cellular oxidative damage where the production of several pro-inflammatory cytokines in cultures cells was greatly reduced. Celastrol significantly increased protein phosphorylation of insulin signaling cascades with amplified expression of AMPK protein and attenuated NF-κB and PKC θ activation in human skeletal muscle treated with AMA. The improvement of insulin signaling pathways by celastrol was also accompanied by augmented GLUT4 protein expression. Taken together, these results suggest that celastrol may be advocated for use as a potential therapeutic molecule to protect against mitochondrial dysfunction-induced insulin resistance in human skeletal muscle cells.

A novel Alaska pollack-derived peptide, which increases glucose uptake in skeletal muscle cells, lowers the blood glucose level in diabetic mice.

Science.gov (United States)

Ayabe, Tatsuhiro; Mizushige, Takafumi; Ota, Wakana; Kawabata, Fuminori; Hayamizu, Kohsuke; Han, Li; Tsuji, Tomoko; Kanamoto, Ryuhei; Ohinata, Kousaku

2015-08-01

We found that the tryptic digest of Alaska pollack protein exhibits a glucose-lowering effect in KK-Ay mice, a type II diabetic model. We then searched for glucose-lowering peptides in the digest. Ala-Asn-Gly-Glu-Val-Ala-Gln-Trp-Arg (ANGEVAQWR) was identified from a peak of the HPLC fraction selected based on the glucose-lowering activity in an insulin resistance test using ddY mice. ANGEVAQWR (3 mg kg(-1)) decreased the blood glucose level after intraperitoneal administration. Among its fragment peptides, the C-terminal tripeptide, Gln-Trp-Arg (QWR, 1 mg kg(-1)), lowered the blood glucose level, suggesting that the C-terminal is critical for glucose-lowering activity. QWR also enhanced glucose uptake into C2C12, a mouse skeletal muscle cell line. QWR did not induce the phosphorylation of serine/threonine protein kinase B (Akt) and adenosine monophosphate-activated protein kinase (AMPK). We also demonstrated that QWR lowered the blood glucose level in NSY and KK-Ay, type II diabetic models.

Exercise, GLUT4, and Skeletal Muscle Glucose Uptake

DEFF Research Database (Denmark)

Richter, Erik; Hargreaves, Mark

2013-01-01

Glucose is an important fuel for contracting muscle, and normal glucose metabolism is vital for health. Glucose enters the muscle cell via facilitated diffusion through the GLUT4 glucose transporter which translocates from intracellular storage depots to the plasma membrane and T-tubules upon...... muscle contraction. Here we discuss the current understanding of how exercise-induced muscle glucose uptake is regulated. We briefly discuss the role of glucose supply and metabolism and concentrate on GLUT4 translocation and the molecular signaling that sets this in motion during muscle contractions....... Contraction-induced molecular signaling is complex and involves a variety of signaling molecules including AMPK, Ca(2+), and NOS in the proximal part of the signaling cascade as well as GTPases, Rab, and SNARE proteins and cytoskeletal components in the distal part. While acute regulation of muscle glucose...

Increments in insulin sensitivity during intensive treatment are closely correlated with decrements in glucocorticoid receptor mRNA in skeletal muscle from patients with Type II diabetes

DEFF Research Database (Denmark)

Vestergaard, H; Bratholm, P; Christensen, N J

2001-01-01

decreased significantly after intensive insulin treatment. A close correlation was found between increments in glucose uptake during intensive treatment and decrements in skeletal muscle total GCR mRNA (r=0.95, Pmultiple regression analysis), and between glucose uptake and alpha/alpha 2 GCR m RNA...

The role of glucose, insulin and NEFA in regulating tissue triglyceride accumulation: Substrate cooperation in adipose tissue versus substrate competition in skeletal muscle.

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Guzzardi, M A; Hodson, L; Guiducci, L; La Rosa, F; Salvadori, P A; Burchielli, S; Iozzo, P

2017-11-01

Metabolic factors initiating adipose tissue expansion and ectopic triglyceride accumulation are not completely understood. We aimed to investigate the independent role of circulating glucose, NEFA and insulin on glucose and NEFA uptake, and lipogenesis in skeletal muscle and subcutaneous adipose tissue (SCAT). Twenty-two pigs were stratified according to four protocols: 1) and 2) low NEFA + high insulin ± high glucose (hyperinsulinaemia-hyperglycaemia or hyperinsulinaemia-euglycaemia), 3) high NEFA + low insulin (fasting), 4) low NEFA + low insulin (nicotinic acid). Positron emission tomography with [ 18 F]fluoro-2-deoxyglucose and [ 11 C]acetate, was combined with [ 14 C]acetate and [U- 13 C]palmitate enrichment techniques to assess glucose and lipid metabolism. Hyperinsulinaemia increased glucose extraction, whilst hyperglycaemia enhanced glucose uptake in skeletal muscle and SCAT. In SCAT, during hyperglycaemia, elevated glucose uptake was accompanied by greater [U- 13 C]palmitate-TG enrichment compared to the other groups, and by a 39% increase in de novo lipogenesis (DNL) compared to baseline, consistent with a 70% increment in plasma lipogenic index. Conversely, in skeletal muscle, [U- 13 C]palmitate-TG enrichment was higher after prolonged fasting. Our data show the necessary role of hyperglycaemia-hyperinsulinaemia vs euglycaemia-hyperinsulinaemia in promoting expansion of TG stores in SCAT, by the consensual elevation in plasma NEFA and glucose uptake and DNL. In contrast, skeletal muscle NEFA uptake for TG synthesis is primarily driven by circulating NEFA levels. These results suggest that a) prolonged fasting or dietary regimens enhancing lipolysis might promote muscle steatosis, and b) the control of glucose levels, in association with adequate energy balance, might contribute to weight loss. Copyright © 2017 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and

The global distribution of leaf chlorophyll content and seasonal controls on carbon uptake

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Croft, H.; Chen, J. M.; Luo, X.; Bartlett, P. A.; Staebler, R. M.; He, L.; Mo, G.; Luo, S.; Simic, A.; Arabian, J.; He, Y.; Zhang, Y.; Beringer, J.; Hutley, L. B.; Noland, T. L.; Arellano, P.; Stahl, C.; Homolová, L.; Bonal, D.; Malenovský, Z.; Yi, Q.; Amiri, R.

2017-12-01

Leaf chlorophyll (ChlLeaf) is crucial to biosphere-atmosphere exchanges of carbon and water, and the functioning of terrestrial ecosystems. Improving the accuracy of modelled photosynthetic carbon uptake is a central priority for understanding ecosystem response to a changing climate. A source of uncertainty within gross primary productivity (GPP) estimates is the failure to explicitly consider seasonal controls on leaf photosynthetic potential. Whilst the inclusion of ChlLeafinto carbon models has shown potential to provide a physiological constraint, progress has been hampered by the absence of a spatially-gridded, global chlorophyll product. Here, we present the first spatially-continuous, global view of terrestrial ChlLeaf, at weekly intervals. Satellite-derived ChlLeaf was modelled using a physically-based radiative transfer modelling approach, with a two stage model inversion method. 4-Scale and SAIL canopy models were first used to model leaf-level reflectance from ENIVSAT MERIS 300m satellite data. The PROSPECT leaf model was then used to derive ChlLeaf from the modelled leaf reflectance. This algorithm was validated using measured ChlLeaf data from 248 measurements within 26 field locations, covering six plant functional types (PFTs). Modelled results show very good relationships with measured data, particularly for deciduous broadleaf forests (R2 = 0.67; pmake an important step towards improving the accuracy of global carbon budgets.

Changes in renal uptake of Tc-99m methylene diphosphonate (MDP) in stone-forming rats

International Nuclear Information System (INIS)

McAfee, J.G.; Thomas, F.D.; Roskopf, M.; Ritter, K.; Lyons, B.; Lilien, O.M.; Schoonmaker, J.E.

1984-01-01

A pyridoxine (vitamin B6)-deficient diet in rats was used as a model of early renal lithiasis to find out if stone-formers could be identified from control animals by differences in the biodistribution of Tc-99m MDP. The mean renal uptake of this agent at 3 hours was about 70% higher in test animals than in controls, but there was considerable overlap between the upper limits of the normal range and lower values in stone-formers. If these results were valid for humans, the metabolic abnormality in males with early stone-forming disease could not be identified with certainty by in vivo measurements of Tc-99m MDP renal uptake alone. However, the skeletal uptake of MDP in the stone-forming animals was depressed by 28 to 35%, compared with control rats. Consequently, the renal to skeletal MDP concentration ratio was invariably elevated in stone-formers beyond the 95 percentile normal range. Unexpectedly, 76% of the pyridoxine-deficient animals had a higher accumulation of MDP in the myocardium than the upper limit of the normal range. The pyridoxine-deficient diet induced no remarkable early changes in the biodistribution or renal clearance of I-131 Hippuran

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

Directory of Open Access Journals (Sweden)

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.

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...

Deep Proteomics of Mouse Skeletal Muscle Enables Quantitation of Protein Isoforms, Metabolic Pathways, and Transcription Factors*

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Deshmukh, Atul S.; Murgia, Marta; Nagaraj, Nagarjuna; Treebak, Jonas T.; Cox, Jürgen; Mann, Matthias

2015-01-01

Skeletal muscle constitutes 40% of individual body mass and plays vital roles in locomotion and whole-body metabolism. Proteomics of skeletal muscle is challenging because of highly abundant contractile proteins that interfere with detection of regulatory proteins. Using a state-of-the art MS workflow and a strategy to map identifications from the C2C12 cell line model to tissues, we identified a total of 10,218 proteins, including skeletal muscle specific transcription factors like myod1 and myogenin and circadian clock proteins. We obtain absolute abundances for proteins expressed in a muscle cell line and skeletal muscle, which should serve as a valuable resource. Quantitation of protein isoforms of glucose uptake signaling pathways and in glucose and lipid metabolic pathways provides a detailed metabolic map of the cell line compared with tissue. This revealed unexpectedly complex regulation of AMP-activated protein kinase and insulin signaling in muscle tissue at the level of enzyme isoforms. PMID:25616865

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

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

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

Recognition of fibrous dysplasia of bone mimicking skeletal metastasis on 18F-FDG PET/CT imaging

International Nuclear Information System (INIS)

Su, Ming Gang; Tian, Rong; Fan, Qiu Ping; Tian, Ye; Li, Fang Lan; Li, Lin; Kuang, An Ren; Miller, John Howard

2011-01-01

Fibrous dysplasia of bone (FDB) reveals intense 18F-FDG uptake mimicking metastases on 18F-FDG PET/CT. We reviewed sites of FDB revealed by 18F-FDG PET/CT imaging to allow identification of this abnormality. Eleven patients (7 male, 4 female, aged 16-78 years) were evaluated after 55 MBq (0.15 mCi)/kg 18F-FDG utilizing a 16-slice multiple detector CT (MDCT) whole-body PET scanner, with LOR algorithm 3D reconstruction. One- and 2-h imaging was performed in 9 patients. Standard uptake value (SUV) for each lesion, on early and delayed imaging, was calculated. Lesions were confirmed in 6 patients by biopsy. The PET images correlated with MDCT to establish the imaging characteristics. Solitary lesions were found in 4 patients, two lesions in 1 patient, and in 6 patients there were multiple bone lesions. The SUV early ranged from 1.23 to 9.64 with an average of 3.76 ± 2.40. The SUV delayed ranged from 1.76 to 11.42 with an average of 4.51 ± 3.07. The SUV delayed decreased or increased slightly (-31% to 5%) in 6 of our patients, and increased significantly (11% to 39%) in 3. There was a negative correlation between SUVs and age, as well as the number of affected bones. In our study, FDB had wide skeletal distribution with variability of 18F-FDG uptake and CT appearance. SUV in the delayed stage was seen to either decrease or increase on dual-time 18F-FDG PET scanning. It is very important to recognize the characteristics of this skeletal dysplasia to allow differentiation from skeletal metastasis. (orig.)

Human skeletal muscle drug transporters determine local exposure and toxicity of statins.

Science.gov (United States)

Knauer, Michael J; Urquhart, Bradley L; Meyer zu Schwabedissen, Henriette E; Schwarz, Ute I; Lemke, Christopher J; Leake, Brenda F; Kim, Richard B; Tirona, Rommel G

2010-02-05

The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, or statins, are important drugs used in the treatment and prevention of cardiovascular disease. Although statins are well tolerated, many patients develop myopathy manifesting as muscle aches and pain. Rhabdomyolysis is a rare but severe toxicity of statins. Interindividual differences in the activities of hepatic membrane drug transporters and metabolic enzymes are known to influence statin plasma pharmacokinetics and risk for myopathy. Interestingly, little is known regarding the molecular determinants of statin distribution into skeletal muscle and its relevance to toxicity. We sought to identify statin transporters in human skeletal muscle and determine their impact on statin toxicity in vitro. We demonstrate that the uptake transporter OATP2B1 (human organic anion transporting polypeptide 2B1) and the efflux transporters, multidrug resistance-associated protein (MRP)1, MRP4, and MRP5 are expressed on the sarcolemmal membrane of human skeletal muscle fibers and that atorvastatin and rosuvastatin are substrates of these transporters when assessed using a heterologous expression system. In an in vitro model of differentiated, primary human skeletal muscle myoblast cells, we demonstrate basal membrane expression and drug efflux activity of MRP1, which contributes to reducing intracellular statin accumulation. Furthermore, we show that expression of human OATP2B1 in human skeletal muscle myoblast cells by adenoviral vectors increases intracellular accumulation and toxicity of statins and such effects were abrogated when cells overexpressed MRP1. These results identify key membrane transporters as modulators of skeletal muscle statin exposure and toxicity.

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...

The proteomic signature of insulin-resistant human skeletal muscle reveals increased glycolytic and decreased mitochondrial enzymes

DEFF Research Database (Denmark)

Giebelstein, J; Poschmann, G; Højlund, K

2012-01-01

The molecular mechanisms underlying insulin resistance in skeletal muscle are incompletely understood. Here, we aimed to obtain a global picture of changes in protein abundance in skeletal muscle in obesity and type 2 diabetes, and those associated with whole-body measures of insulin action....

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...

Insulin stimulation regulates AS160 and TBC1D1 phosphorylation sites in human skeletal muscle

DEFF Research Database (Denmark)

Middelbeek, R J W; Chambers, M A; Tantiwong, P

2013-01-01

Individuals with obesity and type 2 diabetes (T2D) are typically insulin resistant, exhibiting impaired skeletal muscle glucose uptake. Animal and cell culture experiments have shown that site-specific phosphorylation of the Rab-GTPase-activating proteins AS160 and TBC1D1 is critical for GLUT4 tr...

Human skeletal uptake of natural alpha radioactivity from {sup 210}Pb-supported {sup 210}Po

Energy Technology Data Exchange (ETDEWEB)

Oyedepo, A.C

1998-06-01

This thesis contributes to increasing knowledge on the dosimetry of natural alpha-particle radiation in skeletal tissues, particularly in utero, and associated risks of malignancy. Alpha-particle radiation is an established aetiological factor of cancer. In the human body, polonium-210 decayed from skeletal lead-210 ({sup 210}Pb/{sup 210}Po) is the predominant natural alpha-emitter. {sup 210}Pb displaces calcium (Ca) in mineral hydroxyapatite, especially during periods of rapid bone growth and remodelling when Ca is laid down. It was therefore necessary to study alpha activity uptake and calcification concurrently within bone. Human studies were undertaken on: fetal vertebrae, 17 - 42 weeks of gestation, 74 samples; adult vertebrae, 40 - 95 years, 40 samples; and adult ribs, 20 - 95 years, 51 samples. Specimens were unconcentrated and weighed <5 g each. TASTRAK alpha-particle autoradiography was used to assess the bone activity concentration and spatial microdistribution of {sup 210}Pb/{sup 210}Po. Alpha track data were resolved by specially written software named SPATS (Selection Program for Analysing Track Structures). Ca and phosphorus (P) were biochemically determined. Results were examined for trends in bone type, gender and chronological ageing in humans. The main research findings were: 1) The Ca content of fetal vertebrae increased linearly at a weekly rate of 0.2g Ca 100 g{sup -1} wet bone (typical values of 2, 4, 6 g 100 g{sup -1} at 16, 26 and 36 weeks). 2) The P concentration also increased with advancing fetal age. 3) The Ca:P bone weight ratio rose from 1.7 to 2.2 by 32 gestational weeks. 4) The overall range in bone {sup 210}Pb/{sup 210}Po alpha activity was 0.25 - 1.1 Bq kg{sup -1} with correlation between activity concentration and fetal age (0.47 {+-} 0.05 Bq kg{sup -1} for 17 - 26 weeks, 0.67 {+-} 0.04 Bq kg{sup -1} for 32 - 42 weeks). 5) The correlation between increased alpha radioactivity and increased Ca concentration approximating to 0

The effect of high-intensity training on mitochondrial fat oxidation in skeletal muscle and subcutaneous adipose tissue

DEFF Research Database (Denmark)

Larsen, Steen; Danielsen, J H; Søndergård, Stine Dam

2015-01-01

High-intensity interval training (HIT) is known to increase mitochondrial content in a similar way as endurance training [60-90% of maximal oxygen uptake (VO2peak )]. Whether HIT increases the mitochondria's ability to oxidize lipids is currently debated. We investigated the effect of HIT...... of HIT (three times per week at 298 ± 21 W). HIT significantly increased VO2peak from 2.9 ± 0.2 to 3.1 ± 0.2 L/min. No differences were seen in maximal fat oxidation in either skeletal muscle or adipose tissue. Km (app) for octanoyl carnitine or palmitoyl carnitine were similar after training in skeletal...... muscle and adipose tissue. Maximal OXPHOS capacity with complex I- and II-linked substrates was increased after training in skeletal muscle but not in adipose tissue. In conclusion, 6 weeks of HIT increased VO2peak . Mitochondrial content and mitochondrial OXPHOS capacity were increased in skeletal...

Quantitative skeletal scintiscanning

International Nuclear Information System (INIS)

Haushofer, R.

1982-01-01

330 patients were examined by skeletal scintiscanning with sup(99m)Tc pyrophosphate and sup(99m)methylene diphosphonate in the years between 1977 and 1979. Course control examinations were carried out in 12 patients. The collective of patients presented with primary skeletal tumours, metastases, inflammatory and degenerative skeletal diseases. Bone scintiscanning combined with the ''region of interest'' technique was found to be an objective and reproducible technique for quantitative measurement of skeletal radioactivity concentrations. The validity of nuclear skeletal examinations can thus be enhanced as far as diagnosis, course control, and differential diagnosis are concerned. Quantitative skeletal scintiscanning by means of the ''region of interest'' technique has opened up a new era in skeletal diagnosis by nuclear methods. (orig./MG) [de

Comparison of skeletal scintigraphy and radiology for showing the osseous manifestations of generalised mastocytosis

Energy Technology Data Exchange (ETDEWEB)

Bieler, E.U.; Wohlenberg, H.; Utech, C.

1985-05-01

Bone scans and skeletal X-rays of eight patients with systemic mastocytosis were reviewed. Mast cell infiltration of bone marrow had been proven histologically in every patient. Bone scan and roentgenographic findings are not specific for the disease and do not correlate well in some patients. A generalized increase of uptake was noted in two patients, a generalized decrease of skeletal activity with poor delineation of bony structures was observed in others. A circumscribed increase of activity was observed in some patients, only one patient had a normal bone scan. Roentgenographic examination revealed diffuse sclerosis of trabecular bone in three patients, osteoporosis with collaps of multiple vertebral bodies in three patients, and no abnormalities in two patients.

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.

Skeletal muscle phosphatidylcholine and phosphatidylethanolamine respond to exercise and influence insulin sensitivity in men.

Science.gov (United States)

Lee, Sindre; Norheim, Frode; Gulseth, Hanne L; Langleite, Torgrim M; Aker, Andreas; Gundersen, Thomas E; Holen, Torgeir; Birkeland, Kåre I; Drevon, Christian A

2018-04-25

Phosphatidylcholine (PC) and phosphatidylethanolamine (PE) composition in skeletal muscle have been linked to insulin sensitivity. We evaluated the relationships between skeletal muscle PC:PE, physical exercise and insulin sensitivity. We performed lipidomics and measured PC and PE in m. vastus lateralis biopsies obtained from 13 normoglycemic normal weight men and 13 dysglycemic overweight men at rest, immediately after 45 min of cycling at 70% maximum oxygen uptake, and 2 h post-exercise, before as well as after 12 weeks of combined endurance- and strength-exercise intervention. Insulin sensitivity was monitored by euglycemic-hyperinsulinemic clamp. RNA-sequencing was performed on biopsies, and mitochondria and lipid droplets were quantified on electron microscopic images. Exercise intervention for 12 w enhanced insulin sensitivity by 33%, skeletal muscle levels of PC by 21%, PE by 42%, and reduced PC:PE by 16%. One bicycle session reduced PC:PE by 5%. PC:PE correlated negatively with insulin sensitivity (β = -1.6, P insulin sensitivity.

Unexpected myocardial uptake on bone scintigraphy in an infant with Kawasaki disease

International Nuclear Information System (INIS)

Macdonald, W.B.G.; Troedson, R.G.

2003-01-01

Full text: A two-month-old female infant was admitted to hospital because of irritability and poor feeding over the preceding two weeks. There was no history of fever but serum inflammatory markers were elevated and a throat swab yielded a pure growth of Strep, pyogenes. There was no response to antibiotics. The nursing staff noted the infant disliked handling and skeletal pathology was suspected. A bone scan using Tc-99m hydroxymethylene diphosphonate (HDP) showed myocardial activity, with no evidence of abnormal skeletal activity. Subsequent echocardiography showed coronary artery ectasia, typical of Kawasaki disease, with papillary muscle dysfunction, indicating likely myocarditis. A diagnosis of myocarditis secondary to Kawasaki disease was made and the patient promptly improved following intravenous immunoglobulin therapy. Cardiac manifestations of Kawasaki disease included coronary artery aneurysms, myocardial infarction, regional perfusion abnormalities and myocarditis. Myocardial uptake of phosphate tracers is well known following myocardial infarction but there was no wall motion disturbance or ECG abnormality to suggest infarction in this patient and she was felt to have myocarditis. Myocardial uptake of phosphate tracers has not previously been reported in Kawasaki disease. Copyright (2003) The Australian and New Zealand Society of Nuclear Medicine Inc

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

Age-related changes in oxygen and nutrient uptake by hindquarters in newborn pigs during cold-induced shivering.

Science.gov (United States)

Lossec, G; Lebreton, Y; Hulin, J C; Fillaut, M; Herpin, P

1998-11-01

Newborn pigs rely essentially on shivering thermogenesis in the cold. In order to understand the rapid postnatal enhancement of thermogenic capacities in piglets, the oxygen and nutrient uptake of hindquarters was measured in vivo in 1- (n = 6) and 5-day-old (n = 6) animals at thermal neutrality and during cold exposure. The hindquarters were considered to represent a skeletal muscle compartment. Indirect calorimetry and arterio-venous techniques were used. The cold challenge (23 C at 1 day old and 15 C at 5 days old for 90 min) induced a similar increase (+90 %) in regulatory heat production at both ages. Hindquarters blood flow was higher at 5 days than 1 day old at thermal neutrality (26 +/- 3 vs. 17 +/- 1 ml min-1 (100 g hindquarters)-1) and its increase in the cold was much more marked (+65 % at 5 days old vs. +25 % at 1 day old). Oxygen extraction by the hindquarters rose from 30-35 % at thermal neutrality to 65-70 % in the cold at both ages. The calculated contribution of skeletal muscle to total oxygen consumption averaged 34-40 % at thermal neutrality and 50-64 % in the cold and skeletal muscle was the major contributor to regulatory thermogenesis. Based on hindquarters glucose uptake and lactate release, carbohydrate appeared to be an important fuel for shivering. However, net uptake of fatty acids increased progressively during cold exposure at 5 days old. The enhancement in muscular blood supply and fatty acid utilization during shivering is probably related to the postnatal improvement in the thermoregulatory response of the piglet.

Barriers, supports, and effective interventions for uptake of human papillomavirus- and other vaccines within global and Canadian Indigenous peoples: a systematic review protocol.

Science.gov (United States)

Mrklas, Kelly J; MacDonald, Shannon; Shea-Budgell, Melissa A; Bedingfield, Nancy; Ganshorn, Heather; Glaze, Sarah; Bill, Lea; Healy, Bonnie; Healy, Chyloe; Guichon, Juliet; Colquhoun, Amy; Bell, Christopher; Richardson, Ruth; Henderson, Rita; Kellner, James; Barnabe, Cheryl; Bednarczyk, Robert A; Letendre, Angeline; Nelson, Gregg S

2018-03-02

Despite the existence of human papilloma virus (HPV) vaccines with demonstrated safety and effectiveness and funded HPV vaccination programs, coverage rates are persistently lower and cervical cancer burden higher among Canadian Indigenous peoples. Barriers and supports to HPV vaccination in Indigenous peoples have not been systematically documented, nor have interventions to increase uptake in this population. This protocol aims to appraise the literature in Canadian and global Indigenous peoples, relating to documented barriers and supports to vaccination and interventions to increase acceptability/uptake or reduce hesitancy of vaccination. Although HPV vaccination is the primary focus, we anticipate only a small number of relevant studies to emerge from the search and will, therefore, employ a broad search strategy to capture literature related to both HPV vaccination and vaccination in general in global Indigenous peoples. Eligible studies will include global Indigenous peoples and discuss barriers or supports and/or interventions to improve uptake or to reduce hesitancy, for the HPV vaccine and/or other vaccines. Primary outcomes are documented barriers or supports or interventions. All study designs meeting inclusion criteria will be considered, without restricting by language, location, or data type. We will use an a priori search strategy, comprised of key words and controlled vocabulary terms, developed in consultation with an academic librarian, and reviewed by a second academic librarian using the PRESS checklist. We will search several electronic databases from date of inception, without restrictions. A pre-defined group of global Indigenous websites will be reviewed for relevant gray literature. Bibliographic searches will be conducted for all included studies to identify relevant reviews. Data analysis will include an inductive, qualitative, thematic synthesis and a quantitative analysis of measured barriers and supports, as well as a descriptive

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

Glucose metabolism and metabolic flexibility in cultured skeletal muscle cells is related to exercise status in young male subjects

DEFF Research Database (Denmark)

Lund, Jenny; S Tangen, Daniel; Wiig, Håvard

2018-01-01

deoxyglucose accumulation and fractional glucose oxidation (glucose oxidation relative to glucose uptake), and were also more sensitive to the suppressive action of acutely added oleic acid to the cells. Despite lack of correlation of fibre types between skeletal muscle biopsies and cultured cells, myotubes...

Deep proteomics of mouse skeletal muscle enables quantitation of protein isoforms, metabolic pathways, and transcription factors.

Science.gov (United States)

Deshmukh, Atul S; Murgia, Marta; Nagaraj, Nagarjuna; Treebak, Jonas T; Cox, Jürgen; Mann, Matthias

2015-04-01

Skeletal muscle constitutes 40% of individual body mass and plays vital roles in locomotion and whole-body metabolism. Proteomics of skeletal muscle is challenging because of highly abundant contractile proteins that interfere with detection of regulatory proteins. Using a state-of-the art MS workflow and a strategy to map identifications from the C2C12 cell line model to tissues, we identified a total of 10,218 proteins, including skeletal muscle specific transcription factors like myod1 and myogenin and circadian clock proteins. We obtain absolute abundances for proteins expressed in a muscle cell line and skeletal muscle, which should serve as a valuable resource. Quantitation of protein isoforms of glucose uptake signaling pathways and in glucose and lipid metabolic pathways provides a detailed metabolic map of the cell line compared with tissue. This revealed unexpectedly complex regulation of AMP-activated protein kinase and insulin signaling in muscle tissue at the level of enzyme isoforms. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Induced skeletal mutations

International Nuclear Information System (INIS)

Selby, P.B.

1979-01-01

This paper describes a large-scale experiment that, by means of breeding tests, confirmed that many dominant skeletal mutations are induced by large-dose radiation exposure. The author also discusses: (1) the major advantages and disadvantages of the skeletal method in improving estimates of genetic hazard to man; (2) future uses of the skeletal method; (3) direct estimation of risk beyond the first generation using the skeletal method; and (4) the possibility of using the skeletal method as a quick and easy screen for chemical mutagens

Age-related normal uptake of 99mTc-MDP in the lower spine

International Nuclear Information System (INIS)

Sundkvist, G.M.G.; Lilja, B.; Mattsson, S.

1997-01-01

Aim: The uptake of 99m Tc-MDP in the lower spine was quantified in connection with ordinary bone scintigraphy. Methods: Fifty-seven women and seventy-two men (aged 20-69 y), with no signs of metabolic or malignant disease and no history of back pain or atraumatic fractures, were included in the study. Results: The women showed an increase in 99m Tc-MDP uptake from the age of 20 y to about 45 y with a decrease from the time of menopause. In contrast to women, the uptake in men showed a slight decrease from the age of 20 y to about 50 y and thereafter a more marked decrease was seen. The major difference between men and women is the high premenopausal uptake in the female skeleton. Conclusion: An understanding of age-related changes in 99m Tc-MDP uptake, which are indices of the skeletal metabolism, is of importance especially in prevention and treatment of osteoporosis, a common disorder in postmenopausal women. (orig.) [de

Lack of phosphatidylethanolamine N-methyltransferase in mice does not promote fatty acid oxidation in skeletal muscle.

Science.gov (United States)

Tasseva, Guergana; van der Veen, Jelske N; Lingrell, Susanne; Jacobs, René L; Vance, Dennis E; Vance, Jean E

2016-02-01

Phosphatidylethanolamine N-methyltransferase (PEMT) converts phosphatidylethanolamine (PE) to phosphatidylcholine (PC) in the liver. Mice lacking PEMT are protected from high-fat diet-induced obesity and insulin resistance, and exhibit increased whole-body energy expenditure and oxygen consumption. Since skeletal muscle is a major site of fatty acid oxidation and energy utilization, we determined if rates of fatty acid oxidation/oxygen consumption in muscle are higher in Pemt(-/-) mice than in Pemt(+/+) mice. Although PEMT is abundant in the liver, PEMT protein and activity were undetectable in four types of skeletal muscle. Moreover, amounts of PC and PE in the skeletal muscle were not altered by PEMT deficiency. Thus, we concluded that any influence of PEMT deficiency on skeletal muscle would be an indirect consequence of lack of PEMT in liver. Neither the in vivo rate of fatty acid uptake by muscle nor the rate of fatty acid oxidation in muscle explants and cultured myocytes depended upon Pemt genotype. Nor did PEMT deficiency increase oxygen consumption or respiratory function in skeletal muscle mitochondria. Thus, the increased whole body oxygen consumption in Pemt(-/-) mice, and resistance of these mice to diet-induced weight gain, are not primarily due to increased capacity of skeletal muscle for utilization of fatty acids as an energy source. Crown Copyright © 2015. Published by Elsevier B.V. All rights reserved.

Two Cases of Sternal 'Cold' Lesions on Bone Imaging in the Metastatic Skeletal Disease

Energy Technology Data Exchange (ETDEWEB)

Park, Hyung Gun; Seo, Bong Kwan; Lee, Hoon Yong; Lee, Myung Chul; Choi, Sung Jae; Kim, Noe Kyeong; Koh, Chang Soon [Seoul National University College of Medicine, Seoul (Korea, Republic of)

1983-09-15

Traditionally, a positive bone scan shows single or multiple areas of increased uptake in them metastatic skeletal disease. The occurrence of 'cold' lytic-like or photon-deficient lesions in bone imaging is probably uncommon. Photon-deficient focus or cold lesion of the sternum was demonstrated on {sup 99m}Tc-MDP bone imaging in 2 individuals with acute myeloid leukemia and primary hepatoma, respectively.

Extraosseous radiotracer uptake on bone scan in beta-thalassemia: report of one case; Fixation extraosseuse du radiotraceur lors de la realisation d'une scintigraphie du squelette chez un patient atteint de beta-thalassemie: a propos d'un cas

Energy Technology Data Exchange (ETDEWEB)

Guezguez, M.; Nouira, M.; Sfar, R.; Chatti, K.; Ben Fradj, M.; Ben Ali, K.; Ajmi, S.; Essabbah, H. [CHU Sahloul, Service de Medecine Nucleaire, Sousse (Tunisia); Zrour, S. [EPS F. Bourguiba, Service de Rhumatologie, Monastir (Tunisia)

2009-10-15

Red blood cell transfusion, main therapeutic modality of beta-thalassemia, leads to iron overload which may perturb several metabolic ways. The aim of this paper is to illustrate the uptake abnormalities observed on bone scan of thalassaemic patients and to discuss mechanisms of extraosseous accumulation of the radiopharmaceutical in this pathology. We report a 16-year-old child suffering from beta-thalassemia major undergoing transfusion therapy. A bone scan was indicated to look for osseous infection. This study revealed a little skeletal uptake and abnormal liver, splenic and renal accumulation. A repeat bone scan, performed three weeks later showed a better skeletal uptake which enabled the discovery of focal abnormalities and made the diagnostic easier. The effect of iron overload on radiopharmaceuticals uptake in bone scan is known since 1975. Dissociation of {sup 99m}Tc from the carrier ligand due to the presence of iron excess seems the most plausible hypothesis. Free {sup 99m}Tc can be bound to other tissular substrates which can explain extraosseous uptake. The normally available pool for bone is reduced and then the skeletal uptake decreased. This report limits considerably the sensitivity of the bone scan. A well-led iron chelation and eventually the use of diuretic drug may guarantee a better quality of bone scan images. (authors)

Myostatin-deficiency in mice increases global gene expression at the Dlk1-Dio3 locus in the skeletal muscle.

Science.gov (United States)

Hitachi, Keisuke; Tsuchida, Kunihiro

2017-01-24

Myostatin, a member of the transforming growth factor-beta superfamily, is a negative regulator of skeletal muscle growth and development. Myostatin inhibition leads to increased skeletal muscle mass in mammals; hence, myostatin is considered a potential therapeutic target for skeletal muscle wasting. However, downstream molecules of myostatin in the skeletal muscle have not been fully elucidated. Here, we identified the Dlk1-Dio3 locus at the mouse chromosome 12qF1, also called as the callipyge locus in sheep, as a novel downstream target of myostatin. In skeletal muscle of myostatin knockout mice, the expression of mature miRNAs at the Dlk1-Dio3 locus was significantly increased. The increased miRNA levels are caused by the transcriptional activation of the Dlk1-Dio3 locus, because a significant increase in the primary miRNA transcript was observed in myostatin knockout mice. In addition, we found increased expression of coding and non-coding genes (Dlk1, Gtl2, Rtl1/Rtl1as, and Rian) at the Dlk1-Dio3 locus in myostatin-deficient skeletal muscle. Moreover, epigenetic changes, associated with the regulation of the Dlk1-Dio3 locus, were observed in myostatin knockout mice. Taken together, this is the first report demonstrating the role of myostatin in regulating the Dlk1-Dio3 (the callipyge) locus in the skeletal muscle.

Proteomic profiling of non-obese type 2 diabetic skeletal muscle.

Science.gov (United States)

Mullen, Edel; Ohlendieck, Kay

2010-03-01

Abnormal glucose handling has emerged as a major clinical problem in millions of diabetic patients worldwide. Insulin resistance affects especially one of the main target organs of this hormone, the skeletal musculature, making impaired glucose metabolism in contractile fibres a major feature of type 2 diabetes. High levels of circulating free fatty acids, an increased intramyocellular lipid content, impaired insulin-mediated glucose uptake, diminished mitochondrial functioning and an overall weakened metabolic flexibility are pathobiochemical hallmarks of diabetic skeletal muscles. In order to increase our cellular understanding of the molecular mechanisms that underlie this complex diabetes-associated skeletal muscle pathology, we initiated herein a mass spectrometry-based proteomic analysis of skeletal muscle preparations from the non-obese Goto-Kakizaki rat model of type 2 diabetes. Following staining of high-resolution two-dimensional gels with colloidal Coomassie Blue, 929 protein spots were detected, whereby 21 proteins showed a moderate differential expression pattern. Decreased proteins included carbonic anhydrase, 3-hydroxyisobutyrate dehydrogenase and enolase. Increased proteins were identified as monoglyceride lipase, adenylate kinase, Cu/Zn superoxide dismutase, phosphoglucomutase, aldolase, isocitrate dehydrogenase, cytochrome c oxidase, small heat shock Hsp27/B1, actin and 3-mercaptopyruvate sulfurtransferase. These proteomic findings suggest that the diabetic phenotype is associated with a generally perturbed protein expression pattern, affecting especially glucose, fatty acid, nucleotide and amino acid metabolism, as well as the contractile apparatus, the cellular stress response, the anti-oxidant defense system and detoxification mechanisms. The altered expression levels of distinct skeletal muscle proteins, as documented in this study, might be helpful for the future establishment of a comprehensive biomarker signature of type 2 diabetes

Transcriptional adaptations following exercise in Thoroughbred horse skeletal muscle highlights molecular mechanisms that lead to muscle hypertrophy

Directory of Open Access Journals (Sweden)

Park Stephen DE

2009-12-01

Full Text Available Abstract Background Selection for exercise-adapted phenotypes in the Thoroughbred racehorse has provided a valuable model system to understand molecular responses to exercise in skeletal muscle. Exercise stimulates immediate early molecular responses as well as delayed responses during recovery, resulting in a return to homeostasis and enabling long term adaptation. Global mRNA expression during the immediate-response period has not previously been reported in skeletal muscle following exercise in any species. Also, global gene expression changes in equine skeletal muscle following exercise have not been reported. Therefore, to identify novel genes and key regulatory pathways responsible for exercise adaptation we have used equine-specific cDNA microarrays to examine global mRNA expression in skeletal muscle from a cohort of Thoroughbred horses (n = 8 at three time points (before exercise, immediately post-exercise, and four hours post-exercise following a single bout of treadmill exercise. Results Skeletal muscle biopsies were taken from the gluteus medius before (T0, immediately after (T1 and four hours after (T2 exercise. Statistically significant differences in mRNA abundance between time points (T0 vs T1 and T0 vs T2 were determined using the empirical Bayes moderated t-test in the Bioconductor package Linear Models for Microarray Data (LIMMA and the expression of a select panel of genes was validated using real time quantitative reverse transcription PCR (qRT-PCR. While only two genes had increased expression at T1 (P 2 932 genes had increased (P P 2 revealed an over-representation of genes localized to the actin cytoskeleton and with functions in the MAPK signalling, focal adhesion, insulin signalling, mTOR signaling, p53 signaling and Type II diabetes mellitus pathways. At T1, using a less stringent statistical approach, we observed an over-representation of genes involved in the stress response, metabolism and intracellular signaling

The distribution of FDG at PET examinations constitutes a relative mechanism: significant effects at activity quantification in patients with a high muscular uptake

International Nuclear Information System (INIS)

Lindholm, Henry; Johansson, Ove; Jacobsson, Hans; Jonsson, Cathrine

2012-01-01

At 18 F-2-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) examinations a high tracer uptake of the skeletal muscles is sometimes encountered which can lead to reduced uptake in pathological lesions. This was evaluated in retrospect in patients being recalled for a repeat examination after reducing the muscular uptake. Ten patients with increased muscular tracer uptake were examined with FDG PET/CT on two occasions with a mean of 6 days. All patients showed at least one pathological lesion with increased tracer uptake. The muscular uptake was reduced at the second examination by informing the patient to refrain from physical activity together with pretreatment with diazepam. The maximum standardized uptake value (SUV max ) of the pathological lesion and SUV mean of certain skeletal muscles, liver, spleen, lungs, blood and certain bone marrow portions were calculated. In all patients, the muscular uptake was reduced to a normal level at visual evaluation as well as at comparison of SUVs with 25 consecutive clinical patients exhibiting a normal FDG distribution (p max increased from 2.4 to 3.7 (54 %) between the examinations (p max to the activity of any of the reference tissues/organs there was no significant difference between the studies. The distribution of FDG constitutes a relative mechanism. This must be especially considered at longitudinal examinations in the same patient at therapy evaluations. In examinations with a somehow distorted general distribution of the activity, it may be more relevant to relate the lesion activity to a reference tissue/organ than relying on SUV assessments. (orig.)

Effect of alkyl glycerophosphate on the activation of peroxisome proliferator-activated receptor gamma and glucose uptake in C2C12 cells

Energy Technology Data Exchange (ETDEWEB)

Tsukahara, Tamotsu, E-mail: ttamotsu@shinshu-u.ac.jp [Department of Integrative Physiology and Bio-System Control, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano 390-8621 (Japan); Haniu, Hisao [Department of Orthopedic Surgery, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano 390-8621 (Japan); Matsuda, Yoshikazu [Clinical Pharmacology Educational Center, Nihon Pharmaceutical University, Ina-machi, Saitama 362-0806 (Japan)

2013-04-12

Highlights: •Alkyl-LPA specifically interacts with PPARγ. •Alkyl-LPA treatments induces lipid accumulation in C2C12 cells. •Alkyl-LPA enhanced glucose uptake in C2C12 cells. •Alkyl-LPA-treated C2C12 cells express increased amounts of GLUT4 mRNA. •Alkyl-LPA is a novel therapeutic agent that can be used for the treatment of obesity and diabetes. -- Abstract: Studies on the effects of lipids on skeletal muscle cells rarely examine the effects of lysophospholipids. Through our recent studies, we identified select forms of phospholipids, such as alkyl-LPA, as ligands for the intracellular receptor peroxisome proliferator-activated receptor gamma (PPARγ). PPARγ is a nuclear hormone receptor implicated in many human diseases, including diabetes and obesity. We previously showed that alkyl-LPA is a specific agonist of PPARγ. However, the mechanism by which the alkyl-LPA–PPARγ axis affects skeletal muscle cells is poorly defined. Our objective in the present study was to determine whether alkyl-LPA and PPARγ activation promotes glucose uptake in skeletal muscle cells. Our findings indicate that PPARγ1 mRNA is more abundant than PPARγ2 mRNA in C2C12 cells. We showed that alkyl-LPA (3 μM) significantly activated PPARγ and increased intracellular glucose levels in skeletal muscle cells. We also showed that incubation of C2C12 cells with alkyl-LPA led to lipid accumulation in the cells. These findings suggest that alkyl-LPA activates PPARγ and stimulates glucose uptake in the absence of insulin in C2C12 cells. This may contribute to the plasma glucose-lowering effect in the treatment of insulin resistance.

Effect of alkyl glycerophosphate on the activation of peroxisome proliferator-activated receptor gamma and glucose uptake in C2C12 cells

International Nuclear Information System (INIS)

Tsukahara, Tamotsu; Haniu, Hisao; Matsuda, Yoshikazu

2013-01-01

Highlights: •Alkyl-LPA specifically interacts with PPARγ. •Alkyl-LPA treatments induces lipid accumulation in C2C12 cells. •Alkyl-LPA enhanced glucose uptake in C2C12 cells. •Alkyl-LPA-treated C2C12 cells express increased amounts of GLUT4 mRNA. •Alkyl-LPA is a novel therapeutic agent that can be used for the treatment of obesity and diabetes. -- Abstract: Studies on the effects of lipids on skeletal muscle cells rarely examine the effects of lysophospholipids. Through our recent studies, we identified select forms of phospholipids, such as alkyl-LPA, as ligands for the intracellular receptor peroxisome proliferator-activated receptor gamma (PPARγ). PPARγ is a nuclear hormone receptor implicated in many human diseases, including diabetes and obesity. We previously showed that alkyl-LPA is a specific agonist of PPARγ. However, the mechanism by which the alkyl-LPA–PPARγ axis affects skeletal muscle cells is poorly defined. Our objective in the present study was to determine whether alkyl-LPA and PPARγ activation promotes glucose uptake in skeletal muscle cells. Our findings indicate that PPARγ1 mRNA is more abundant than PPARγ2 mRNA in C2C12 cells. We showed that alkyl-LPA (3 μM) significantly activated PPARγ and increased intracellular glucose levels in skeletal muscle cells. We also showed that incubation of C2C12 cells with alkyl-LPA led to lipid accumulation in the cells. These findings suggest that alkyl-LPA activates PPARγ and stimulates glucose uptake in the absence of insulin in C2C12 cells. This may contribute to the plasma glucose-lowering effect in the treatment of insulin resistance

Skeletal blood flow, iliac histomorphometry, and strontium kinetics in osteoporosis: a relationship between blood flow and corrected apposition rate

International Nuclear Information System (INIS)

Reeve, J.; Arlot, M.; Wootton, R.; Edouard, C.; Tellez, M.; Hesp, R.; Green, J.R.; Meunier, P.J.

1988-01-01

In 20 untreated patients with idiopathic or postmenopausal osteoporosis, kinetic studies of skeletal blood flow (using 18 F) and bone turnover (using 85 Sr) were combined with dynamic histomorphometry performed on transiliac biopsies taken within 6 weeks of each other. In 8 patients the combined studies were repeated after treatment. A further 5 patients were studied only while receiving treatment. As expected, skeletal blood flow measured by 18 F correlated with an index of 85 Sr uptake into the exchangeable pools of bone. Additionally and independently, skeletal blood flow correlated with an index of the work rate of the osteoblasts in each multicellular unit of bone (the corrected apposition rate of Parfitt). These correlations were statistically significant in both the untreated patients (P less than 0.05) and the whole group (P less than 0.001). Further indices related to bone turnover at the level of the skeleton as a whole were significantly associated with skeletal blood flow only in the combined group

Skeletal carbonate mineralogy of Scottish bryozoans

Science.gov (United States)

Spencer Jones, Mary; Najorka, Jens; Smith, Abigail M.

2018-01-01

This paper describes the skeletal carbonate mineralogy of 156 bryozoan species collected from Scotland (sourced both from museum collections and from waters around Scotland) and collated from literature. This collection represents 79% of the species which inhabit Scottish waters and is a greater number and proportion of extant species than any previous regional study. The study is also of significance globally where the data augment the growing database of mineralogical analyses and offers first analyses for 26 genera and four families. Specimens were collated through a combination of field sampling and existing collections and were analysed by X-ray diffraction (XRD) and micro-XRD to determine wt% MgCO3 in calcite and wt% aragonite. Species distribution data and phylogenetic organisation were applied to understand distributional, taxonomic and phylo-mineralogical patterns. Analysis of the skeletal composition of Scottish bryozoans shows that the group is statistically different from neighbouring Arctic fauna but features a range of mineralogy comparable to other temperate regions. As has been previously reported, cyclostomes feature low Mg in calcite and very little aragonite, whereas cheilostomes show much more variability, including bimineralic species. Scotland is a highly variable region, open to biological and environmental influx from all directions, and bryozoans exhibit this in the wide range of within-species mineralogical variability they present. This plasticity in skeletal composition may be driven by a combination of environmentally-induced phenotypic variation, or physiological factors. A flexible response to environment, as manifested in a wide range of skeletal mineralogy within a species, may be one characteristic of successful invasive bryozoans. PMID:29897916

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.

The yield of high-detail radiographic skeletal surveys in suspected infant abuse

International Nuclear Information System (INIS)

Barber, Ignasi; Perez-Rossello, Jeannette M.; Kleinman, Paul K.; Wilson, Celeste R.

2015-01-01

Skeletal surveys are routinely performed in cases of suspected child abuse, but there are limited data regarding the yield of high-detail skeletal surveys in infants. To determine the diagnostic yield of high-detail radiographic skeletal surveys in suspected infant abuse. We reviewed the high-detail American College of Radiology standardized skeletal surveys performed for suspected abuse in 567 infants (median: 4.4 months, SD 3.47; range: 4 days-12 months) at a large urban children's hospital between 2005 and 2013. Skeletal survey images, radiology reports and medical records were reviewed. A skeletal survey was considered positive when it showed at least one unsuspected fracture. In 313 of 567 infants (55%), 1,029 definite fractures were found. Twenty-one percent (119/567) of the patients had a positive skeletal survey with a total of 789 (77%) unsuspected fractures. Long-bone fractures were the most common injuries, present in 145 children (26%). The skull was the site of fracture in 138 infants (24%); rib cage in 77 (14%), clavicle in 24 (4.2%) and uncommon fractures (including spine, scapula, hands and feet and pelvis) were noted in 26 infants (4.6%). Of the 425 infants with neuroimaging, 154 (36%) had intracranial injury. No significant correlation between positive skeletal survey and associated intracranial injury was found. Scapular fractures and complex skull fractures showed a statistically significant correlation with intracranial injury (P = 0.029, P = 0.007, respectively). Previously unsuspected fractures are noted on skeletal surveys in 20% of cases of suspected infant abuse. These data may be helpful in the design and optimization of global skeletal imaging in this vulnerable population. (orig.)

The yield of high-detail radiographic skeletal surveys in suspected infant abuse

Energy Technology Data Exchange (ETDEWEB)

Barber, Ignasi [Hospital Vall d' Hebron, Universitat Autonoma de Barcelona, Pediatric Radiology Department, Barcelona (Spain); Perez-Rossello, Jeannette M.; Kleinman, Paul K. [Boston Children' s Hospital, Radiology Department, Boston, MA (United States); Wilson, Celeste R. [Boston Children' s Hospital, Division of General Pediatrics, Boston, MA (United States)

2014-07-06

Skeletal surveys are routinely performed in cases of suspected child abuse, but there are limited data regarding the yield of high-detail skeletal surveys in infants. To determine the diagnostic yield of high-detail radiographic skeletal surveys in suspected infant abuse. We reviewed the high-detail American College of Radiology standardized skeletal surveys performed for suspected abuse in 567 infants (median: 4.4 months, SD 3.47; range: 4 days-12 months) at a large urban children's hospital between 2005 and 2013. Skeletal survey images, radiology reports and medical records were reviewed. A skeletal survey was considered positive when it showed at least one unsuspected fracture. In 313 of 567 infants (55%), 1,029 definite fractures were found. Twenty-one percent (119/567) of the patients had a positive skeletal survey with a total of 789 (77%) unsuspected fractures. Long-bone fractures were the most common injuries, present in 145 children (26%). The skull was the site of fracture in 138 infants (24%); rib cage in 77 (14%), clavicle in 24 (4.2%) and uncommon fractures (including spine, scapula, hands and feet and pelvis) were noted in 26 infants (4.6%). Of the 425 infants with neuroimaging, 154 (36%) had intracranial injury. No significant correlation between positive skeletal survey and associated intracranial injury was found. Scapular fractures and complex skull fractures showed a statistically significant correlation with intracranial injury (P = 0.029, P = 0.007, respectively). Previously unsuspected fractures are noted on skeletal surveys in 20% of cases of suspected infant abuse. These data may be helpful in the design and optimization of global skeletal imaging in this vulnerable population. (orig.)

Diffuse Myocardial Uptake of 99mTc-HDP in Multiple Myeloma

International Nuclear Information System (INIS)

Demirel, Koray; Sadic, Murat; Korkmaz, Meliha; Comak, Aylin; Atilgan, Hasan Ikbal; Koca, Goekhan

2013-01-01

Soft tissue uptake is a rare finding in bone scintigraphy, with an incidence of 2%. Although the mechanism has not yet been fully clarified, several causes have been reported for this unusual uptake pattern. This paper presents a case of diffuse myocardial accumulation of technetium-99m hydroxymethylene diphosphonate ( 99m Tc-HDP) without either solid/visceral organ or soft tissue with multiple myeloma (MM) in skeletal scintigraphy. A 93-year-old man with hypertension and chronic heart failure for 14 years underwent bone scanning due to a 2-month history of back pain within a 1-year period of MM. Three hours later, 99m Tc-HDP late static images showed diffuse myocardial radiotracer accumulation and there were no other sites of abnormal soft tissue or visceral uptake. Myocardial accumulation had disappeared on 24-h delayed static images. This accumulation was thought to be related with AL-type amyloidosis associated with MM

Acclimation temperature affects the metabolic response of amphibian skeletal muscle to insulin.

Science.gov (United States)

Petersen, Ann M; Gleeson, Todd T

2011-09-01

Frog skeletal muscle mainly utilizes the substrates glucose and lactate for energy metabolism. The goal of this study was to determine the effect of insulin on the uptake and metabolic fate of lactate and glucose at rest in skeletal muscle of the American bullfrog, Lithobates catesbeiana, under varying temperature regimens. We hypothesize that lactate and glucose metabolic pathways will respond differently to the presence of insulin in cold versus warm acclimated frog tissues, suggesting an interaction between temperature and metabolism under varying environmental conditions. We employed radiolabeled tracer techniques to measure in vitro uptake, oxidation, and incorporation of glucose and lactate into glycogen by isolated muscles from bullfrogs acclimated to 5 °C (cold) or 25 °C (warm). Isolated bundles from Sartorius muscles were incubated at 5 °C, 15 °C, or 25 °C, and in the presence and absence of 0.05 IU/mL bovine insulin. Insulin treatment in the warm acclimated and incubated frogs resulted in an increase in glucose incorporation into glycogen, and an increase in intracellular [glucose] of 0.5 μmol/g (Pmuscle. When compared to the warm treatment group, cold acclimation and incubation resulted in increased rates of glucose oxidation and glycogen synthesis, and a reduction in free intracellular glucose levels (Pmuscles from either acclimation group were incubated at an intermediate temperature of 15 °C, insulin's effect on substrate metabolism was attenuated or even reversed. Therefore, a significant interaction between insulin and acclimation condition in controlling skeletal muscle metabolism appears to exist. Our findings further suggest that one of insulin's actions in frog muscle is to increase glucose incorporation into glycogen, and to reduce reliance on lactate as the primary metabolic fuel. Copyright © 2011 Elsevier Inc. All rights reserved.

A Modified method for reducing renal injury in zoledronic acid treatment of hypercalcemia and adverse skeletal events

Directory of Open Access Journals (Sweden)

Jiang Liu

2013-01-01

Full Text Available Aims: In this paper, we have reported a previously undescribed risk factor of deterioration of renal function in zoledronic acid treatment of skeletal metastasis - high serum calcium level. Based on this consideration, a modified method of treatment of hypercalcemia (HCM with zoledronic acid is suggested in this paper. Material and Methods: Bone scan findings of 1090 cancer patients were analyzed, of which 26 had intense renal parenchymal uptake as a result of HCM or bone metastases. Subsequently, a total of 56 bone metastases patients with zoledronic acid treatment were divided into three groups: HCM group who were pre-treated to normal serum calcium level (13 patients, HCM group (19 patients, and normal serum calcium group (24 patients. Results: More patients with intense renal parenchymal uptake were hyperglycemic, statistically significantly (18/26 versus 19/1064, P = 2.1, E-78. No more patients with intense renal parenchymal uptake were associated with bone metastases (14/26 versus 438/1064, P = 0.20. Subsequently, more HCM patients receiving zoledronic acid treatment showed renal injury compared to patients with normal serum calcium level (5/15 versus 2/24, P < 0.05 and HCM patients with pre-treatment to normal serum calcium level (5/15 versus 1/17, P < 0.05. Conclusions: Intense renal parenchymal uptake of bisphosphonates is closely related to HCM rather than to bone metastases in cancer patients. The serum calcium should be measured and reduced to normal level before zoledronic acid is used in managements of adverse skeletal events in order to decrease the risk of renal injury.

Comprehensive Validation of Skeletal Mechanism for Turbulent Premixed Methane–Air Flame Simulations

KAUST Repository

Luca, Stefano

2017-08-01

A new skeletal mechanism, consisting of 16 species and 72 reactions, has been developed for lean methane–air premixed combustion from the GRI-Mech 3.0. The skeletal mechanism is validated for elevated unburnt temperatures (800 K) and pressures up to 4 atm, thereby addressing realistic gas turbine conditions. The skeletal mechanism is obtained by applying the directed relation graph method and performing sensitivity analysis on the detailed mechanism. The mechanism has been validated for flame speed and flame structure in a wide range of conditions and configurations. A good agreement between the skeletal mechanism and GRI-3.0 was obtained. The configurations considered include one-dimension laminar premixed flames, laminar non-premixed counterflow burners, and two- and three-dimensional unsteady configurations with variations of temperature, pressure, and composition. The skeletal mechanism allows for the inclusion of accurate finite rate chemistry in large-scale direct numerical simulations of lean turbulent premixed flames. In a large-scale direct numerical simulation, the use of the skeletal mechanism reduces the memory requirements by more than a factor of 3 and accelerates the simulation by a factor of 7 compared with the detailed mechanism. The skeletal mechanism is suitable for unsteady three-dimensional simulations of methane turbulent premixed, non-premixed, and globally lean partially premixed flames and is available as supplementary material.

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.

Quantification of radionuclide uptake levels for primary bone tumors

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Hasford Francis

2015-04-01

Full Text Available The purpose of the study is to quantify the level of uptake of administered radionuclide in primary bone tumors for patients undergoing bone scintigraphy. Retrospective study on 48 patient's scintigrams to quantify the uptake levels of administered radiopharmaceuticals was performed in a nuclear medicine unit in Ghana. Patients were administered with activity ranging between 0.555 and 1.110 MBq (15–30 mCi, and scanned on Siemens e.cam SPECT system. Analyses on scintigrams were performed with Image J software by drawing regions of interest (ROIs over identified hot spots (pathologic sites. Nine skeletal parts namely cranium, neck, shoulder, sacrum, sternum, vertebra, femur, ribcage, and knee were considered in the study, which involved 96 identified primary tumors. Radionuclide uptakes were quantified in terms of the estimated counts of activity per patient for identified tumor sites. Average normalized counts of activity (nGMC per patient ranged from 5.2759 ± 0.6590 cts/mm2/MBq in the case of cranium tumors to 72.7569 ± 17.8786 cts/mm2/MBq in the case of ribcage tumors. The differences in uptake levels could be attributed to different mechanisms of Tc-99m MDP uptake in different types of bones, which is directly related to blood flow and degree of osteoblastic activity. The overall normalized count of activity for the 96 identified tumors was estimated to be 23.0350 ± 19.5424 cts/mm2/MBq. The study revealed highest uptake of activity in ribcage and least uptake in cranium. Quantification of radionuclide uptakes in tumors is important and recommended in assessing patient's response to therapy, doses to critical organs and in diagnosing tumors.

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.

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

Regulation of the concentration of 3H-ouabain binding sites in mammalian skeletal muscle

International Nuclear Information System (INIS)

Kjeldsen, K.

1986-01-01

The major purpose of the present study was the identification and quantification of changes in Na,K-pumps in skeletal muscles with age, K-depletion and thyroid status. Furthermore, the putative difference in skeletal muscle Na,K-pump concentration between spontaneously hypertensive rats and normotensive controls was investigated. On the basis of the observation of major changes in 3 H-ouabain binding site concentration in skeletal muscle with age, K-depletion and thyroid status and the large increase in skeletal muscle Na/K-ratio with K-depletion, the consequences of these variations for cell properties, K-homeostasis and digitalis distribution was evaluated. The present investigation was carried out mainly by measurements of Na,K-pump concentrations, Na,K-contents and K-uptake in skeletal muscles. Hitherto, the Na,K-pump concentration in muscle has mainly been quantified by measurements of the Na,K-ATPase activity in purified membrane fractions. The use of such preparations are, however, complicated by a recovery of plasma membranes of often less than 5% of that in intact tissue. Although this low yield may not affect the interpretation of qualitative studies, it represents a potentially large source of error in quantitative determinations of the Na,K-pumps. Thus, in the present study the Na,K-pumps were quantified by measurements of 3 -ouabain binding, as this method allows the determination of the total Na,K-pump concentration after identification and correction for methodological problems. (author)

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...

Effects of reperfusion intervals on skeletal muscle injury beneath and distal to a pneumatic tourniquet.

Science.gov (United States)

Pedowitz, R A; Gershuni, D H; Fridén, J; Garfin, S R; Rydevik, B L; Hargens, A R

1992-03-01

To date there have been no experimental studies specifically directed at effects of reperfusion intervals on skeletal muscle injury beneath the tourniquet. 99mTechnetium pyrophosphate (Tc 99) incorporation and correlative histology were used to assess injury 2 days after tourniquet application in muscles beneath (thigh) and distal (leg) to the cuff. Tourniquets were applied to rabbit hindlimbs for a total of either 2 or 4 hours. In the 4-hour series, tourniquet compression (either 125 mm Hg or 350 mm Hg cuff inflation pressure) was either continuous or interrupted by 10-minute reperfusion intervals after 2 hours or after every hour of cuff inflation. In the 2-hour series, tourniquet compression (350 mm Hg) was either continuous or interrupted by 10-minute reperfusion intervals after 2 hours or after every hour of cuff inflation. In the 2-hour series, tourniquet compression (350 mm Hg) was either continuous or interrupted by a 10-minute reperfusion interval after 1 hour. Pyrophosphate incorporation (Tc 99 uptake) was significantly greater in the thigh region than in the leg region in all of the 4-hour tourniquet groups. Tc 99 uptake was significantly reduced by reperfusion after each hour of cuff inflation. With 350 mm Hg tourniquet pressure, a reperfusion interval after 2 hours of cuff inflation tended to exacerbate tourniquet compression injury. Reperfusion intervals did not significantly affect Tc 99 uptake in the leg region of these groups. With a 2-hour tourniquet time, Tc 99 uptake in the thigh was significantly decreased by reperfusion after 1 hour of cuff inflation. Previous clinical recommendations, based on serum creatine phosphokinase abnormalities after experimental tourniquet ischemia, probably reflected tourniquet compression injury. Hourly reperfusion limits skeletal muscle injury during extended periods of tourniquet use.

Quantitative studies of skeletal muscle lactate metabolism

International Nuclear Information System (INIS)

Pagliassotti, M.J.

1988-01-01

In Situ, single-pass perfusions were employed on three isolated rabbit skeletal muscle preparations of differing fiber type and oxidative capacity to investigate the influence of fiber type and oxidative capacity per se on net carbon, 14 C-lactate, and 3 H-glucose fluxes. Preparations were exposed to six lactate concentrations ranging from 1-11mM. At basal lactate concentrations all preparations displayed net lactate release, 14 C-lactate removal and 14 CO 2 release, all were linearly correlated with lactate concentration. By 4mM all preparations switched to net lactate uptake and 14 C-lactate removal always exceeded net lactate uptake. To quantify the fate of net carbon, 14 C-lactate, and 3 H-glucose removal preparations were perfused at either basal or elevated lactate. Under basal conditions net carbon influx from glucose and glycogen was removed primarily via net lactate release in the glycolytic and mixed preparations and oxidation and net lactate release in the oxidative preparation. At elevated lactate, net carbon influx from lactate, pyruvate and glucose was removed primarily by net glycogen synthesis in the glycolytic preparation and both alanine release and oxidation in the mixed and oxidative preparations

Changes in skeletal muscle gene expression following clenbuterol administration

Directory of Open Access Journals (Sweden)

McIntyre Lauren M

2006-12-01

Full Text Available Abstract Background Beta-adrenergic receptor agonists (BA induce skeletal muscle hypertrophy, yet specific mechanisms that lead to this effect are not well understood. The objective of this research was to identify novel genes and physiological pathways that potentially facilitate BA induced skeletal muscle growth. The Affymetrix platform was utilized to identify gene expression changes in mouse skeletal muscle 24 hours and 10 days after administration of the BA clenbuterol. Results Administration of clenbuterol stimulated anabolic activity, as indicated by decreased blood urea nitrogen (BUN; P P Conclusion Global evaluation of gene expression after administration of clenbuterol identified changes in gene expression and overrepresented functional categories of genes that may regulate BA-induced muscle hypertrophy. Changes in mRNA abundance of multiple genes associated with myogenic differentiation may indicate an important effect of BA on proliferation, differentiation, and/or recruitment of satellite cells into muscle fibers to promote muscle hypertrophy. Increased mRNA abundance of genes involved in the initiation of translation suggests that increased levels of protein synthesis often associated with BA administration may result from a general up-regulation of translational initiators. Additionally, numerous other genes and physiological pathways were identified that will be important targets for further investigations of the hypertrophic effect of BA on skeletal muscle.

Double stranded viral RNA induces inflammation and insulin resistance in skeletal muscle from pregnant women in vitro.

Science.gov (United States)

Lappas, Martha

2015-05-01

Maternal peripheral insulin resistance and increased inflammation are two features of pregnancies complicated by pre-existing maternal obesity and gestational diabetes mellitus (GDM). There is now increasing evidence that activation of Toll-like receptor (TLR) signalling pathways by viral products may play a role in the pathophysiology of diabetes. Thus, the aim of this study was to assess the effect of the TLR3 ligand and viral dsRNA analogue polyinosinic polycytidilic acid (poly(I:C)) on inflammation and the insulin signalling pathway in skeletal muscle from pregnant women. Human skeletal muscle tissue explants were performed to determine the effect of poly(I:C) on the expression and secretion of markers of inflammation, and the insulin signalling pathway and glucose uptake. Poly(I:C) significantly increased the expression of a number of inflammatory markers in skeletal muscle from pregnant women. Specifically, there was an increase in the expression and/or secretion of the pro-inflammatory cytokines TNF-α, and IL-6 and the pro-inflammatory chemokines IL-8 and MCP-1. These effect of poly(I:C) appear to mediated via a number of signalling molecules including the pro-inflammatory transcription factor NF-κB, and the serine threonine kinases GSK3 and AMPKα. Additionally, poly(I:C) decreased insulin stimulated GLUT-4 expression and glucose uptake in skeletal muscle from pregnant women. The in vitro data presented in this study suggests that viral infection may contribute to the pathophysiology of pregnancies complicated by pre-existing maternal obesity and/or GDM. It should be noted that the in vitro studies cannot be directly used to infer the same outcomes in the intact subject. Copyright © 2015 Elsevier Inc. All rights reserved.

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....

Serum Is Not Necessary for Prior Pharmacological Activation of AMPK to Increase Insulin Sensitivity of Mouse Skeletal Muscle

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Nicolas O. Jørgensen

2018-04-01

Full Text Available Exercise, contraction, and pharmacological activation of AMP-activated protein kinase (AMPK by 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR have all been shown to increase muscle insulin sensitivity for glucose uptake. Intriguingly, improvements in insulin sensitivity following contraction of isolated rat and mouse skeletal muscle and prior AICAR stimulation of isolated rat skeletal muscle seem to depend on an unknown factor present in serum. One study recently questioned this requirement of a serum factor by showing serum-independency with muscle from old rats. Whether a serum factor is necessary for prior AICAR stimulation to increase insulin sensitivity of mouse skeletal muscle is not known. Therefore, we investigated the necessity of serum for this effect of AICAR in mouse skeletal muscle. We found that the ability of prior AICAR stimulation to improve insulin sensitivity of mouse skeletal muscle did not depend on the presence of serum during AICAR stimulation. Although prior AICAR stimulation did not enhance proximal insulin signaling, insulin-stimulated phosphorylation of Tre-2/BUB2/CDC16- domain family member 4 (TBC1D4 Ser711 was greater in prior AICAR-stimulated muscle compared to all other groups. These results imply that the presence of a serum factor is not necessary for prior AMPK activation by AICAR to enhance insulin sensitivity of mouse skeletal muscle.

Diffuse Myocardial Uptake of {sup 99m}Tc-HDP in Multiple Myeloma

Energy Technology Data Exchange (ETDEWEB)

Demirel, Koray; Sadic, Murat; Korkmaz, Meliha; Comak, Aylin; Atilgan, Hasan Ikbal; Koca, Goekhan [Ministry of Health Ankara Training and Research Hospital, Ankara (Turkmenistan)

2013-09-15

Soft tissue uptake is a rare finding in bone scintigraphy, with an incidence of 2%. Although the mechanism has not yet been fully clarified, several causes have been reported for this unusual uptake pattern. This paper presents a case of diffuse myocardial accumulation of technetium-99m hydroxymethylene diphosphonate ({sup 99m}Tc-HDP) without either solid/visceral organ or soft tissue with multiple myeloma (MM) in skeletal scintigraphy. A 93-year-old man with hypertension and chronic heart failure for 14 years underwent bone scanning due to a 2-month history of back pain within a 1-year period of MM. Three hours later, {sup 99m}Tc-HDP late static images showed diffuse myocardial radiotracer accumulation and there were no other sites of abnormal soft tissue or visceral uptake. Myocardial accumulation had disappeared on 24-h delayed static images. This accumulation was thought to be related with AL-type amyloidosis associated with MM.

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

OpenAIRE

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

2007-01-01

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 to oxidativ...

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)

Contraction regulates site-specific phosphorylation of TBC1D1 in skeletal muscle.

Science.gov (United States)

Vichaiwong, Kanokwan; Purohit, Suneet; An, Ding; Toyoda, Taro; Jessen, Niels; Hirshman, Michael F; Goodyear, Laurie J

2010-10-15

TBC1D1 (tre-2/USP6, BUB2, cdc16 domain family member 1) is a Rab-GAP (GTPase-activating protein) that is highly expressed in skeletal muscle, but little is known about TBC1D1 regulation and function. We studied TBC1D1 phosphorylation on three predicted AMPK (AMP-activated protein kinase) phosphorylation sites (Ser231, Ser660 and Ser700) and one predicted Akt phosphorylation site (Thr590) in control mice, AMPKα2 inactive transgenic mice (AMPKα2i TG) and Akt2-knockout mice (Akt2 KO). Muscle contraction significantly increased TBC1D1 phosphorylation on Ser231 and Ser660, tended to increase Ser700 phosphorylation, but had no effect on Thr590. AICAR (5-aminoimidazole-4-carboxyamide ribonucleoside) also increased phosphorylation on Ser231, Ser660 and Ser700, but not Thr590, whereas insulin only increased Thr590 phosphorylation. Basal and contraction-stimulated TBC1D1 Ser231, Ser660 and Ser700 phosphorylation were greatly reduced in AMPKα2i TG mice, although contraction still elicited a small increase in phosphorylation. Akt2 KO mice had blunted insulin-stimulated TBC1D1 Thr590 phosphorylation. Contraction-stimulated TBC1D1 Ser231 and Ser660 phosphorylation were normal in high-fat-fed mice. Glucose uptake in vivo was significantly decreased in tibialis anterior muscles overexpressing TBC1D1 mutated on four predicted AMPK phosphorylation sites. In conclusion, contraction causes site-specific phosphorylation of TBC1D1 in skeletal muscle, and TBC1D1 phosphorylation on AMPK sites regulates contraction-stimulated glucose uptake. AMPK and Akt regulate TBC1D1 phosphorylation, but there must be additional upstream kinases that mediate TBC1D1 phosphorylation in skeletal muscle.

Variability of insulin-stimulated myocardial glucose uptake in healthy elderly subjects

DEFF Research Database (Denmark)

Kofoed, Klaus F; Hove, Jens D; Freiberg, Jacob

2002-01-01

The aim of this study was to assess regional and global variability of insulin-stimulated myocardial glucose uptake in healthy elderly subjects and to evaluate potentially responsible factors. Twenty men with a mean age of 64 years, no history of cardiovascular disease, and normal blood pressure...... rest and hyperaemic blood flow during dipyridamole infusion were measured with nitrogen-13 ammonia and positron emission tomography in 16 left ventricular myocardial segments. Intra-individual and inter-individual variability of insulin-stimulated myocardial glucose uptake [relative dispersion...... = (standard deviation/mean)] was 13% and 29% respectively. Although inter-individual variability of glucose uptake and blood flow at rest was of the same magnitude, no correlation was found between these measures. Regional and global insulin-stimulated myocardial glucose uptake correlated linearly with whole...

FDG-PET/CT assessment of differential chemotherapy effects upon skeletal muscle metabolism in patients with melanoma

International Nuclear Information System (INIS)

Goncalves, M.D.; Alavi, A.; Torigian, D.A.

2014-01-01

To quantify the differential effects of chemotherapy on the metabolic activity of skeletal muscle in vivo using molecular imaging with [18F]-fluorodeoxy-glucose (FDG)-positron emission tomography/computed tomography (PET/CT). In this retrospective study, 21 subjects with stage IV melanoma who underwent pre- and post-chemotherapy whole-body FDG-PET/CT imaging were included. The mean standardized uptake value (SUV mean ) of 8 different skeletal muscles was measured per subject. Pre- and post-treatment measurements were then averaged across all subjects for each muscle and compared for statistically significant differences between the muscles and following different chemotherapy regimens including dacarbazine (DTIC) and temozolomide (TMZ). Analysis of FDG-PET/CT images reliably detected changes in skeletal muscle metabolic activity based on muscle location. The percent change in metabolic activity of each skeletal muscle in each subject following chemotherapy was observed to be related to the type of chemotherapy received. Subjects receiving DTIC generally had a decrease in metabolic activity of all muscle groups, whereas subjects receiving TMZ generally had an increase in muscle activity of all muscle groups. FDG-PET/CT can reveal baseline metabolic differences between different muscles of the body. Different chemotherapies are associated with differential changes in the metabolic activity of skeletal muscle, which can be detected and quantified with FDG-PET/CT. (author)

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....

Simplified data access on human skeletal muscle transcriptome responses to differentiated exercise

DEFF Research Database (Denmark)

Vissing, Kristian; Schjerling, Peter

2014-01-01

Few studies have investigated exercise-induced global gene expression responses in human skeletal muscle and these have typically focused at one specific mode of exercise and not implemented non-exercise control models. However, interpretation on effects of differentiated exercise necessitate dir...

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...

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.

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

Factors determining the oxygen consumption rate (VO2) on-kinetics in skeletal muscles.

OpenAIRE

Korzeniewski, Bernard; Zoladz, Jerzy A

2004-01-01

Using a computer model of oxidative phosphorylation developed previously [Korzeniewski and Mazat (1996) Biochem. J. 319, 143-148; Korzeniewski and Zoladz (2001) Biophys. Chem. 92, 17-34], we analyse the effect of several factors on the oxygen-uptake kinetics, especially on the oxygen consumption rate (VO2) and half-transition time t(1/2), at the onset of exercise in skeletal muscles. Computer simulations demonstrate that an increase in the total creatine pool [PCr+/-Cr] (where Cr stands for c...

Recombinant Uncarboxylated Osteocalcin Per Se Enhances Mouse Skeletal Muscle Glucose Uptake in both Extensor Digitorum Longus and Soleus Muscles

Directory of Open Access Journals (Sweden)

Xuzhu Lin

2017-11-01

Full Text Available Emerging evidence suggests that undercarboxylated osteocalcin (ucOC improves muscle glucose uptake in rodents. However, whether ucOC can directly increase glucose uptake in both glycolytic and oxidative muscles and the possible mechanisms of action still need further exploration. We tested the hypothesis that ucOC per se stimulates muscle glucose uptake via extracellular signal-regulated kinase (ERK, adenosine monophosphate-activated protein kinase (AMPK, and/or the mechanistic target of rapamycin complex 2 (mTORC2-protein kinase B (AKT-AKT substrate of 160 kDa (AS160 signaling cascade. Extensor digitorum longus (EDL and soleus muscles from male C57BL/6 mice were isolated, divided into halves, and then incubated with ucOC with or without the pretreatment of ERK inhibitor U0126. ucOC increased muscle glucose uptake in both EDL and soleus. It also enhanced phosphorylation of ERK2 (Thr202/Tyr204 and AS160 (Thr642 in both muscle types and increased mTOR phosphorylation (Ser2481 in EDL only. ucOC had no significant effect on the phosphorylation of AMPKα (Thr172. The inhibition of ucOC-induced ERK phosphorylation had limited effect on ucOC-stimulated glucose uptake and AS160 phosphorylation in both muscle types, but appeared to inhibit the elevation in AKT phosphorylation only in EDL. Taken together, ucOC at the physiological range directly increased glucose uptake in both EDL and soleus muscles in mouse. The molecular mechanisms behind this ucOC effect on muscle glucose uptake seem to be muscle type-specific, involving enhanced phosphorylation of AS160 but limitedly modulated by ERK phosphorylation. Our study suggests that, since ucOC increases muscle glucose uptake without insulin, it could be considered as a potential agent to improve muscle glucose uptake in insulin resistant conditions.

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...

A Bayesian Approach to Multistage Fitting of the Variation of the Skeletal Age Features

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Dong Hua

2009-01-01

Full Text Available Accurate assessment of skeletal maturity is important clinically. Skeletal age assessment is usually based on features encoded in ossification centers. Therefore, it is critical to design a mechanism to capture as much as possible characteristics of features. We have observed that given a feature, there exist stages of the skeletal age such that the variation pattern of the feature differs in these stages. Based on this observation, we propose a Bayesian cut fitting to describe features in response to the skeletal age. With our approach, appropriate positions for stage separation are determined automatically by a Bayesian approach, and a model is used to fit the variation of a feature within each stage. Our experimental results show that the proposed method surpasses the traditional fitting using only one line or one curve not only in the efficiency and accuracy of fitting but also in global and local feature characterization.

Skeletal muscle tissue engineering: methods to form skeletal myotubes and their applications.

Science.gov (United States)

Ostrovidov, Serge; Hosseini, Vahid; Ahadian, Samad; Fujie, Toshinori; Parthiban, Selvakumar Prakash; Ramalingam, Murugan; Bae, Hojae; Kaji, Hirokazu; Khademhosseini, Ali

2014-10-01

Skeletal muscle tissue engineering (SMTE) aims to repair or regenerate defective skeletal muscle tissue lost by traumatic injury, tumor ablation, or muscular disease. However, two decades after the introduction of SMTE, the engineering of functional skeletal muscle in the laboratory still remains a great challenge, and numerous techniques for growing functional muscle tissues are constantly being developed. This article reviews the recent findings regarding the methodology and various technical aspects of SMTE, including cell alignment and differentiation. We describe the structure and organization of muscle and discuss the methods for myoblast alignment cultured in vitro. To better understand muscle formation and to enhance the engineering of skeletal muscle, we also address the molecular basics of myogenesis and discuss different methods to induce myoblast differentiation into myotubes. We then provide an overview of different coculture systems involving skeletal muscle cells, and highlight major applications of engineered skeletal muscle tissues. Finally, potential challenges and future research directions for SMTE are outlined.

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

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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.

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.

Increase in observed net carbon dioxide uptake by land and oceans during the past 50 years.

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Ballantyne, A P; Alden, C B; Miller, J B; Tans, P P; White, J W C

2012-08-02

One of the greatest sources of uncertainty for future climate predictions is the response of the global carbon cycle to climate change. Although approximately one-half of total CO(2) emissions is at present taken up by combined land and ocean carbon reservoirs, models predict a decline in future carbon uptake by these reservoirs, resulting in a positive carbon-climate feedback. Several recent studies suggest that rates of carbon uptake by the land and ocean have remained constant or declined in recent decades. Other work, however, has called into question the reported decline. Here we use global-scale atmospheric CO(2) measurements, CO(2) emission inventories and their full range of uncertainties to calculate changes in global CO(2) sources and sinks during the past 50 years. Our mass balance analysis shows that net global carbon uptake has increased significantly by about 0.05 billion tonnes of carbon per year and that global carbon uptake doubled, from 2.4 ± 0.8 to 5.0 ± 0.9 billion tonnes per year, between 1960 and 2010. Therefore, it is very unlikely that both land and ocean carbon sinks have decreased on a global scale. Since 1959, approximately 350 billion tonnes of carbon have been emitted by humans to the atmosphere, of which about 55 per cent has moved into the land and oceans. Thus, identifying the mechanisms and locations responsible for increasing global carbon uptake remains a critical challenge in constraining the modern global carbon budget and predicting future carbon-climate interactions.

A study on the development of normal mandible in children by skeletal scintigraphy

International Nuclear Information System (INIS)

Gao Yiming; Qiu Weiliu; Shen Guofang; Tang Yousheng; Tian Weijia; Wang Hui; Feng Guowei; Pu Mingfang

2000-01-01

Objective: To study the developmental characters of the normal mandible in growing children. Methods: Twenty growing children undergoing skeletal scintigraphic study for isolated bone disease other than bones of the head and neck at hospital and turned out with normal results finally were studied. The 99 Tc m -MDP uptakes in the mandibular condyle, ramus, body and the fourth lumbar vertebra in these cases were quantitated and a ratio of the uptake in the three mandibular regions to that in the fourth lumbar vertebra was obtained. Results: The analysis results showed that the 99 Tc m -MDP uptake ratios of the three mandibular regions decreased in linear fashion with age increasing and leveled off after age of 20. The regression equations are: the mandibular condyle, Y-circumflex = -0.052 2X + 1.792 8; the mandibular ramus, Y-circumflex = -0.015 1X + 0.766 7; the mandibular body, Y-circumflex = -0.014 2X + 0.741 0. There was no significant difference of the 99 Tc m -MDP uptake ratio between the two sides of the mandible and between the male and female. Conclusion: The results suggest that the ideal time to undergo orthognathic surgery should be at the age of 20 or so if the circumstance of the deformity is not quite clear

Modulation of liver mitochondrial NOS is implicated in thyroid-dependent regulation of O(2) uptake.

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Carreras, M C; Peralta, J G; Converso, D P; Finocchietto, P V; Rebagliati, I; Zaninovich, A A; Poderoso, J J

2001-12-01

Changes in O(2) uptake at different thyroid status have been explained on the basis of the modulation of mitochondrial enzymes and membrane biophysical properties. Regarding the nitric oxide (NO) effects, we tested whether liver mitochondrial nitric oxide synthase (mtNOS) participates in the modulation of O(2) uptake in thyroid disorders. Wistar rats were inoculated with 400 microCi (131)I (hypothyroid group), 20 microg thyroxine (T(4))/100 g body wt administered daily for 2 wk (hyperthyroid group) or vehicle (control). Basal metabolic rate, mitochondrial function, and mtNOS activity were analyzed. Systemic and liver mitochondrial O(2) uptake and cytochrome oxidase activity were lower in hypothyroid rats with respect to controls; mitochondrial parameters were further decreased by L-arginine (-42 and -34%, P activity (260%) were selectively increased in hypothyroidism and reverted by hormone replacement without changes in other nitric oxide isoforms. Moreover, mtNOS activity correlated with serum 3,5,3'-triiodothyronine (T(3)) and O(2) uptake. Increased mtNOS activity was also observed in skeletal muscle mitochondria from hypothyroid rats. Therefore, we suggest that modulation of mtNOS is a substantial part of thyroid effects on mitochondrial O(2) uptake.

Uptake of labelled tallysomycin by solid Ehrlich ascites tumors in mice

International Nuclear Information System (INIS)

Liniecki, J.; Rembelska, M.; Koniarek, B.

1983-01-01

Tumor and normal tissue uptake of 51 Cr- or 57 Co-labelled bleomycin (BLEO) and tallysomycin (TLM) was compared in female solid Ehrlich ascites tumor mice of Swiss strain. The complexes were administered intraperitoneally: 30-50 μg of each complex with an activity of 40-120 μCi. Activity distribution factors (ADF) and tumor/non-tumor ratios for blood, bone, skeletal muscles, kidneys and liver were determined. The ratios were generally higher for complexes labelled with 57 Co than for the 51 Cr-labelled ones; bleomycin appears equivalent or superior to tallysomycin. (orig.) [de

Targeted overexpression of mitochondrial catalase protects against cancer chemotherapy-induced skeletal muscle dysfunction.

Science.gov (United States)

Gilliam, Laura A A; Lark, Daniel S; Reese, Lauren R; Torres, Maria J; Ryan, Terence E; Lin, Chien-Te; Cathey, Brook L; Neufer, P Darrell

2016-08-01

The loss of strength in combination with constant fatigue is a burden on cancer patients undergoing chemotherapy. Doxorubicin, a standard chemotherapy drug used in the clinic, causes skeletal muscle dysfunction and increases mitochondrial H2O2 We hypothesized that the combined effect of cancer and chemotherapy in an immunocompetent breast cancer mouse model (E0771) would compromise skeletal muscle mitochondrial respiratory function, leading to an increase in H2O2-emitting potential and impaired muscle function. Here, we demonstrate that cancer chemotherapy decreases mitochondrial respiratory capacity supported with complex I (pyruvate/glutamate/malate) and complex II (succinate) substrates. Mitochondrial H2O2-emitting potential was altered in skeletal muscle, and global protein oxidation was elevated with cancer chemotherapy. Muscle contractile function was impaired following exposure to cancer chemotherapy. Genetically engineering the overexpression of catalase in mitochondria of muscle attenuated mitochondrial H2O2 emission and protein oxidation, preserving mitochondrial and whole muscle function despite cancer chemotherapy. These findings suggest mitochondrial oxidants as a mediator of cancer chemotherapy-induced skeletal muscle dysfunction. Copyright © 2016 the American Physiological Society.

Selenium Uptake and Volatilization by Marine Algae

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Luxem, Katja E.; Vriens, Bas; Wagner, Bettina; Behra, Renata; Winkel, Lenny H. E.

2015-04-01

Selenium (Se) is an essential trace nutrient for humans. An estimated one half to one billion people worldwide suffer from Se deficiency, which is due to low concentrations and bioavailability of Se in soils where crops are grown. It has been hypothesized that more than half of the atmospheric Se deposition to soils is derived from the marine system, where microorganisms methylate and volatilize Se. Based on model results from the late 1980s, the atmospheric flux of these biogenic volatile Se compounds is around 9 Gt/year, with two thirds coming from the marine biosphere. Algae, fungi, and bacteria are known to methylate Se. Although algal Se uptake, metabolism, and methylation influence the speciation and bioavailability of Se in the oceans, these processes have not been quantified under environmentally relevant conditions and are likely to differ among organisms. Therefore, we are investigating the uptake and methylation of the two main inorganic Se species (selenate and selenite) by three globally relevant microalgae: Phaeocystis globosa, the coccolithophorid Emiliania huxleyi, and the diatom Thalassiosira oceanica. Selenium uptake and methylation were quantified in a batch experiment, where parallel gas-tight microcosms in a climate chamber were coupled to a gas-trapping system. For E. huxleyi, selenite uptake was strongly dependent on aqueous phosphate concentrations, which agrees with prior evidence that selenite uptake by phosphate transporters is a significant Se source for marine algae. Selenate uptake was much lower than selenite uptake. The most important volatile Se compounds produced were dimethyl selenide, dimethyl diselenide, and dimethyl selenyl sulfide. Production rates of volatile Se species were larger with increasing intracellular Se concentration and in the decline phase of the alga. Similar experiments are being carried out with P. globosa and T. oceanica. Our results indicate that marine algae are important for the global cycling of Se

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...

Evaluation of solitary rib lesions in CA. breast patients for development of skeletal metastasis

International Nuclear Information System (INIS)

Fatima, A.; Fatima, S.; Khursheed, K.; Jafri, S.; Asghar, S.

2004-01-01

Determination of nature of single or double rib lesion on a bone scan is important but very difficult. In case of breast carcinoma rib lesion have particular importance, as they are one of the most common sites of metastasis. On the contrary surgical trauma and radiotherapy can induce metabolic changes, which can lead to rib lesions of benign etiology. As it is known that breast carcinoma patients having skeletal metastasis have worse prognosis so it is particularly important to differentiate between malignant and benign rib lesions. In this study etiology of rib lesions detected on bone scan was analyzed retrospectively patients. Study population consisted of breast cancer patients having solitary rib lesions on baseline or follow-up bone scan were included in the study. The etiology of solitary rib involvement was established using all the clinical, radiological and biochemical data available. The clinical and serial scintigraphic data were collected and analyzed for correlation in forty-two patients. Patients were followed up for at least two subsequent bone scans. Out of total study population nine patients (21.42%) developed skeletal metastasis on follow-up. Rest of the study population is disease free till last follow-up. All these patients developed metastasis within two years of appearance of the rib lesions. Correlation between sites of initial rib lesion, uptake pattern, size of tumor, mode of primary therapy, age of involvement, interval from initial therapy, biochemical and radiological findings was done. Correlation was seen between sites of uptake, uptake pattern, mode of primary therapy and biochemical findings with subsequent outcome of the patient. It is concluded from our study that solitary rib lesion have low incidence of malignancy if other risk factors are absent. (authors)

Proteomics of Skeletal Muscle

DEFF Research Database (Denmark)

Deshmukh, Atul

2016-01-01

, of altered protein expressions profiles and/or their posttranslational modifications (PTMs). Mass spectrometry (MS)-based proteomics offer enormous promise for investigating the molecular mechanisms underlying skeletal muscle insulin resistance and exercise-induced adaptation; however, skeletal muscle......Skeletal muscle is the largest tissue in the human body and plays an important role in locomotion and whole body metabolism. It accounts for ~80% of insulin stimulated glucose disposal. Skeletal muscle insulin resistance, a primary feature of Type 2 diabetes, is caused by a decreased ability...... of muscle to respond to circulating insulin. Physical exercise improves insulin sensitivity and whole body metabolism and remains one of the most promising interventions for the prevention of Type 2 diabetes. Insulin resistance and exercise adaptations in skeletal muscle might be a cause, or consequence...

Skeletal surveys in multiple myeloma

International Nuclear Information System (INIS)

Sebes, J.I.; Niell, H.B.; Palmieri, G.M.A.; Reidy, T.J.

1986-01-01

Thirty-three patients with multiple myeloma were studied with serial skeletal surveys, serum immunoglobulin levels, and postabsorptive urinary hydroxyproline (Spot-HYPRO) determinations. Twenty receiving chemotherapy were also followed with skeletal surveys in order to evaluate bone response to treatment. A close association was found between skeletal findings and changes in immunoglubulin levels with positive correlation in 71% of the patients. A similar association was found between skeletal disease and Spot-HYPRO level changes in 65%. Five of 12 patients (42%) with partial or complete clinical response to chemotherapy, demonstrated improvement in the appearance of skeletal lesions. Positive correlation between the roentgenographic changes and clinical markers of myeloma as well as therapeutic response, indicates that skeletal surveys are useful and effective in monitoring patients with multiple myeloma. (orig.)

A short period of high-intensity interval training improves skeletal muscle mitochondrial function and pulmonary oxygen uptake kinetics

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Christensen, Peter Møller; Jacobs, Robert A; Bonne, Thomas Christian

2016-01-01

The aim of the present study was to examine whether improvements in pulmonary V̇O2 kinetics following a short period of high-intensity training (HIT) would be associated with improved skeletal muscle mitochondrial function. Ten untrained male volunteers (age: 26 ± 2; mean ± SD) performed six HIT...

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.

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

Whole-body MRI in comparison to skeletal scintigraphy for detection of skeletal metastases in patients with solid tumors

International Nuclear Information System (INIS)

Ghanem, N.; Altehoefer, C.; Winterer, J.; Schaefer, O.; Bley, T.A.; Langer, M.; Kelly, T.; Moser, E.

2004-01-01

The aim of this study was to compare the diagnostic efficacy of whole-body magnetic resonance imaging (WB-MRI) as a new and rapid examination technique with skeletal scintigraphy for detection of skeletal metastases from solid tumors. In 129 patients with solid malignant tumors, WB-MRI was performed for individual comparison with skeletal scintigraphy. Examinations were performed with the innovative AngioSURF trademark rolling table with integrated phased array surface coil and coronary TIRM sequences for different body regions. The results for WB-MRI and skeletal scintigraphy were concordant in 81% of the cases, whereby both procedures excluded skeletal metastases in 43%. WB-MRI and skeletal scintigraphy demonstrated skeletal metastases in 38% of the cases, whereby WB-MRI provided more comprehensive findings in 45%. In 12% of the cases, skeletal scintigraphy was superior to WB-MRI and in 19% the findings were discordant, whereby WB-MRI detected skeletal metastases in 15 cases which had not been found on skeletal scintigraphy. In nine cases, skeletal scintigraphy was positive when the WB-MRI was negative. In 60% of the cases, WB-MRI evidenced tumor-associated findings. WB-MRI represents a promising new staging technique for detection of skeletal metastases, which is more sensitive in many cases than skeletal scintigraphy in detecting and assessing the extent of skeletal metastases - and tumor-associated findings that are relevant for treatment strategy. (orig.) [de

Biochemical background of the VO2 on-kinetics in skeletal muscles.

Science.gov (United States)

Korzeniewski, Bernard; Zoladz, Jerzy A

2006-02-01

This review discusses the present knowledge on the oxygen uptake kinetics at the onset of exercise in skeletal muscle and the contribution of a previously developed computer model of oxidative phosphorylation in intact skeletal muscle to the understanding of the factors determining this kinetics on the biochemical level. It has been demonstrated recently that an increase in the total creatine pool [PCr + Cr] and in glycolytic ATP supply lengthen the half-transition time of the VO2 on-kinetics, while an increase in mitochondria content, in parallel activation of ATP supply and ATP usage, in muscle oxygen concentration, in proton leak, in resting energy demand, in resting cytosolic pH, and in initial alkalization diminish this parameter. It has also been shown that the half-transition time is near-linearly proportional to the absolute difference between the phosphocreatine concentration during work and at rest (deltaPCr). The present review discusses whether the V/O2 on-kinetics on the muscle level is strictly or only approximately exponential. Finally, it is postulated that a short transition time of the VO2 on-kinetics in itself does not need be profitable for the skeletal muscle functioning during exercise, but usually a short transition time is correlated with factors that improve exercise capacity. The transition time is a phenomenological parameter resulting from the biochemical properties of the system and not a physical factor that can cause anything in the system.

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....

Hypoxia in Combination With Muscle Contraction Improves Insulin Action and Glucose Metabolism in Human Skeletal Muscle via the HIF-1α Pathway.

Science.gov (United States)

Görgens, Sven W; Benninghoff, Tim; Eckardt, Kristin; Springer, Christian; Chadt, Alexandra; Melior, Anita; Wefers, Jakob; Cramer, Andrea; Jensen, Jørgen; Birkeland, Kåre I; Drevon, Christian A; Al-Hasani, Hadi; Eckel, Jürgen

2017-11-01

Skeletal muscle insulin resistance is the hallmark of type 2 diabetes and develops long before the onset of the disease. It is well accepted that physical activity improves glycemic control, but the knowledge on underlying mechanisms mediating the beneficial effects remains incomplete. Exercise is accompanied by a decrease in intramuscular oxygen levels, resulting in induction of HIF-1α. HIF-1α is a master regulator of gene expression and might play an important role in skeletal muscle function and metabolism. Here we show that HIF-1α is important for glucose metabolism and insulin action in skeletal muscle. By using a genome-wide gene expression profiling approach, we identified RAB20 and TXNIP as two novel exercise/HIF-1α-regulated genes in skeletal muscle. Loss of Rab20 impairs insulin-stimulated glucose uptake in human and mouse skeletal muscle by blocking the translocation of GLUT4 to the cell surface. In addition, exercise/HIF-1α downregulates the expression of TXNIP , a well-known negative regulator of insulin action. In conclusion, we are the first to demonstrate that HIF-1α is a key regulator of glucose metabolism in skeletal muscle by directly controlling the transcription of RAB20 and TXNIP These results hint toward a novel function of HIF-1α as a potential pharmacological target to improve skeletal muscle insulin sensitivity. © 2017 by the American Diabetes Association.

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.

Associations between insulin resistance and TNF-alpha in plasma, skeletal muscle and adipose tissue in humans with and without type 2 diabetes

DEFF Research Database (Denmark)

Plomgaard, P; Nielsen, A R; Fischer, C P

2007-01-01

AIMS/HYPOTHESIS: Clear evidence exists that TNF-alpha inhibits insulin signalling and thereby glucose uptake in myocytes and adipocytes. However, conflicting results exist with regard to the role of TNF-alpha in type 2 diabetes. METHODS: We obtained blood and biopsy samples from skeletal muscle...... and subcutaneous adipose tissue in patients with type 2 diabetes (n = 96) and healthy controls matched for age, sex and BMI (n = 103). RESULTS: Patients with type 2 diabetes had higher plasma levels of fasting insulin (p ...) uptake (VO2/kg) in the diabetes group (p type 2 diabetic patients. Immunohistochemistry revealed more TNF-alpha protein...

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

Directory of Open Access Journals (Sweden)

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

Elevated CO2 plus chronic warming reduce nitrogen uptake and levels or activities of nitrogen-uptake and -assimilatory proteins in tomato roots.

Science.gov (United States)

Jayawardena, Dileepa M; Heckathorn, Scott A; Bista, Deepesh R; Mishra, Sasmita; Boldt, Jennifer K; Krause, Charles R

2017-03-01

Atmospheric CO 2 enrichment is expected to often benefit plant growth, despite causing global warming and nitrogen (N) dilution in plants. Most plants primarily procure N as inorganic nitrate (NO 3 - ) or ammonium (NH 4 + ), using membrane-localized transport proteins in roots, which are key targets for improving N use. Although interactive effects of elevated CO 2 , chronic warming and N form on N relations are expected, these have not been studied. In this study, tomato (Solanum lycopersicum) plants were grown at two levels of CO 2 (400 or 700 ppm) and two temperature regimes (30 or 37°C), with NO 3 - or NH 4 + as the N source. Elevated CO 2 plus chronic warming severely inhibited plant growth, regardless of N form, while individually they had smaller effects on growth. Although %N in roots was similar among all treatments, elevated CO 2 plus warming decreased (1) N-uptake rate by roots, (2) total protein concentration in roots, indicating an inhibition of N assimilation and (3) shoot %N, indicating a potential inhibition of N translocation from roots to shoots. Under elevated CO 2 plus warming, reduced NO 3 - -uptake rate per g root was correlated with a decrease in the concentration of NO 3 - -uptake proteins per g root, reduced NH 4 + uptake was correlated with decreased activity of NH 4 + -uptake proteins and reduced N assimilation was correlated with decreased concentration of N-assimilatory proteins. These results indicate that elevated CO 2 and chronic warming can act synergistically to decrease plant N uptake and assimilation; hence, future global warming may decrease both plant growth and food quality (%N). © 2016 Scandinavian Plant Physiology Society.

Global and regional ocean carbon uptake and climate change: sensitivity to a substantial mitigation scenario

Energy Technology Data Exchange (ETDEWEB)

Vichi, Marcello; Masina, Simona; Navarra, Antonio [Centro Euro-Mediterraneo per i Cambiamenti Climatici (CMCC), Bologna (Italy); Istituto Nazionale di Geofisica e Vulcanologia, Bologna (Italy); Manzini, Elisa [Centro Euro-Mediterraneo per i Cambiamenti Climatici (CMCC), Bologna (Italy); Istituto Nazionale di Geofisica e Vulcanologia, Bologna (Italy); Max Planck Institute for Meteorology, Hamburg (Germany); Fogli, Pier Giuseppe [Centro Euro-Mediterraneo per i Cambiamenti Climatici (CMCC), Bologna (Italy); Alessandri, Andrea [Centro Euro-Mediterraneo per i Cambiamenti Climatici (CMCC), Bologna (Italy); ENEA, Rome (Italy); Patara, Lavinia [Centro Euro-Mediterraneo per i Cambiamenti Climatici (CMCC), Bologna (Italy); Leibniz Institute of Marine Sciences (IFM-GEOMAR), Kiel (Germany); Scoccimarro, Enrico [Istituto Nazionale di Geofisica e Vulcanologia, Bologna (Italy)

2011-11-15

Under future scenarios of business-as-usual emissions, the ocean storage of anthropogenic carbon is anticipated to decrease because of ocean chemistry constraints and positive feedbacks in the carbon-climate dynamics, whereas it is still unknown how the oceanic carbon cycle will respond to more substantial mitigation scenarios. To evaluate the natural system response to prescribed atmospheric ''target'' concentrations and assess the response of the ocean carbon pool to these values, 2 centennial projection simulations have been performed with an Earth System Model that includes a fully coupled carbon cycle, forced in one case with a mitigation scenario and the other with the SRES A1B scenario. End of century ocean uptake with the mitigation scenario is projected to return to the same magnitude of carbon fluxes as simulated in 1960 in the Pacific Ocean and to lower values in the Atlantic. With A1B, the major ocean basins are instead projected to decrease the capacity for carbon uptake globally as found with simpler carbon cycle models, while at the regional level the response is contrasting. The model indicates that the equatorial Pacific may increase the carbon uptake rates in both scenarios, owing to enhancement of the biological carbon pump evidenced by an increase in Net Community Production (NCP) following changes in the subsurface equatorial circulation and enhanced iron availability from extratropical regions. NCP is a proxy of the bulk organic carbon made available to the higher trophic levels and potentially exportable from the surface layers. The model results indicate that, besides the localized increase in the equatorial Pacific, the NCP of lower trophic levels in the northern Pacific and Atlantic oceans is projected to be halved with respect to the current climate under a substantial mitigation scenario at the end of the twenty-first century. It is thus suggested that changes due to cumulative carbon emissions up to present and the

Quantitative Assessment of Radioisotope Uptake in Condyles by SPECT Bone Scintigraphy

Directory of Open Access Journals (Sweden)

Z. Dalili

2006-03-01

Full Text Available Statement of problem: Condylar hyperplasia of the mandible is a self limiting abnormality which can cause facial asymmetry, temporomandibular joint (TMJdysfunction and esthetic problems. Treatment planning is based on the results of isotope scanning, clinical findings and patient age. Single photon emission tomography(SPECT is considered to be a sensitive method in the calculation of condylar uptake differences.Purpose: The aim of this study was to determine the growth activity occurring in the mandibular condyles, and to devise an index of side-to-side differences in condylar activity in different individuals.Material and Methods: 38 patients, with an age range of 13 to 34 years, undergoing skeletal scintigraphy for a variety of conditions, were chosen for this study. 25 mci TC-99 was injected to all subjects in order to assess the difference between right (Rt andleft (Lt condylar uptake percentage and to calculate the Lt to Rt condylar uptake ratio.The normal index was determined.Results: The maximum amount of difference between the uptake of Rt and Lt condyles was 6.2 percent (Lt side and Rt side were 53.1 % and 46.9 %, respectively in the male patients and 5.7 percent in the female patients (Lt side and Rt side were 52.85 % and 47.15 %, respectively. The condylar activity difference and ratio of Lt to Rt condylar uptakes did not show a significant difference between the male and female groups.Conclusion: The difference between the growth activity of RT and LT normal TMJs was less than 6.2 percent.

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.

Single Hind Limb Burn Injury to Mice Alters NF Kappa B (NF-κB) Expression and [18F] 2-Fluoro-2-Deoxy-d-Glucose (FDG) Uptake

Science.gov (United States)

Carter, Edward A.; Hamrahi, Victoria; Paul, Kasie; Bonab, Ali A.; Jung, Walter; Tompkins, Ronald G.; Fischman, Alan J.

2014-01-01

Burn trauma to the extremities can produce marked systemic effects in mice1, 6, 7. Burn injury to the dorsal surface of mice is also associated with changes in glucose metabolism (18FDG uptake) by brown adipose tissue (BAT) and NF-κB activity in a number of tissues including skeletal muscle. This study examined the effect of a single hindlimb burn in mice on 18FDG uptake by in vivo, NF-κB activity in vivo, and blood flow determined by laser Doppler techniques. Male mice NF-κB luciferase reporter mice (28 grams- 30 grams, male) were anesthetized, both legs were shaven, and the right leg was subjected to scald injury by immersion in 90°C water for 5 seconds. Sham treated animals were used as controls. Each burned and sham mouse was resuscitated with saline (2 ml, IP). The individual animals were placed in wire bottom cages with no food and free access to water. 24 hrs later, the animals were imaged with Laser Doppler for measurements of blood flow in the hind limb. The animals were then injected unanesthetized with 50 µCi of FDG or luciferin (1.0 mg), I.V. via tail vein. Five minutes after luciferin injection, NF-kB mice were studied by bioluminescence imaging with a CCD camera. One hour after 18FDG injection the animals were euthanized with carbon dioxide overdose and 18FDG biodistribution was measured. Tissues were also analyzed for NF-κB luciferase activity. The scalding procedure used here produced a full thickness burn injury to the leg with sharp margins. 18FDG uptake by the burned leg was lower than in the contralateral limb. Similarly luciferase activity and blood flow in the burned leg were lower than in the contralateral leg. 18FDG uptake by BAT and heart was increased, while brain was decreased. In conclusion, the present study suggests that burn injury to a single leg reduced 18FDG uptake by skeletal muscle but increased 18FDG uptake by BAT. The injury to the leg reduced NF-κB expression as compared to the contralateral leg and the uninjured

Skeletal muscle proteomics: current approaches, technical challenges and emerging techniques

LENUS (Irish Health Repository)

Ohlendieck, Kay

2011-02-01

Abstract Background Skeletal muscle fibres represent one of the most abundant cell types in mammals. Their highly specialised contractile and metabolic functions depend on a large number of membrane-associated proteins with very high molecular masses, proteins with extensive posttranslational modifications and components that exist in highly complex supramolecular structures. This makes it extremely difficult to perform conventional biochemical studies of potential changes in protein clusters during physiological adaptations or pathological processes. Results Skeletal muscle proteomics attempts to establish the global identification and biochemical characterisation of all members of the muscle-associated protein complement. A considerable number of proteomic studies have employed large-scale separation techniques, such as high-resolution two-dimensional gel electrophoresis or liquid chromatography, and combined them with mass spectrometry as the method of choice for high-throughput protein identification. Muscle proteomics has been applied to the comprehensive biochemical profiling of developing, maturing and aging muscle, as well as the analysis of contractile tissues undergoing physiological adaptations seen in disuse atrophy, physical exercise and chronic muscle transformation. Biomedical investigations into proteome-wide alterations in skeletal muscle tissues were also used to establish novel biomarker signatures of neuromuscular disorders. Importantly, mass spectrometric studies have confirmed the enormous complexity of posttranslational modifications in skeletal muscle proteins. Conclusions This review critically examines the scientific impact of modern muscle proteomics and discusses its successful application for a better understanding of muscle biology, but also outlines its technical limitations and emerging techniques to establish new biomarker candidates.

Global Forum 2015 dialogue on "From evidence to policy - thinking outside the box": perspectives to improve evidence uptake and good practices in the African Region.

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Kirigia, Joses Muthuri; Pannenborg, Charles Ok; Amore, Luis Gabriel Cuervo; Ghannem, Hassen; IJsselmuiden, Carel; Nabyonga-Orem, Juliet

2016-07-18

The Global Forum 2015 panel session dialogue entitled "From evidence to policy - thinking outside the box" was held on 26 August 2015 in the Philippines to debate why evidence was not fully translated into policy and practice and what could be done to increase its uptake. This paper reports the reasons and possible actions for increasing the uptake of evidence, and highlights the actions partners could take to increase the use of evidence in the African Region. The Global Forum 2015 debate attributed African Region's low uptake of evidence to the big gap in incentives and interests between research for health researchers and public health policy-makers; limited appreciation on the side of researchers that public health decisions are based on multiple and complex considerations; perception among users that research evidence is not relevant to local contexts; absence of knowledge translation platforms; sub-optimal collaboration and engagement between industry and research institutions; lack of involvement of civil society organizations; lack of engagement of communities in the research process; failure to engage the media; limited awareness and debate in national and local parliaments on the importance of investing in research and innovation; and dearth of research and innovation parks in the African Region. The actions needed in the Region to increase the uptake of evidence in policy and practice include strengthening NHRS governance; bridging the motivation gap between researchers and health policy-makers; restoring trust between researchers and decision-makers; ensuring close and continuous intellectual intercourse among researchers, ministry of health policy-makers and technocrats during the life course of research projects or programmes; proactive collaboration between academia and industry; regular briefings of civil society, media, relevant parliamentary committees and development partners; development of vibrant knowledge translation platforms; development of

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.

Science.gov (United States)

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.

Increased mitochondrial substrate sensitivity in skeletal muscle of patients with type 2 diabetes

DEFF Research Database (Denmark)

Larsen, S; Stride, N; Hey-Mogensen, Martin

2011-01-01

AIMS/HYPOTHESIS: Mitochondrial respiration has been linked to insulin resistance. We studied mitochondrial respiratory capacity and substrate sensitivity in patients with type 2 diabetes (patients), and obese and lean control participants. METHODS: Mitochondrial respiration was measured.......4). Substrate sensitivity for octanoyl-carnitine did not differ between groups. CONCLUSIONS/INTERPRETATION: Increased mitochondrial substrate sensitivity is seen in skeletal muscle from type 2 diabetic patients and is confined to non-lipid substrates. Respiratory capacity per mitochondrion is not decreased...... and maximal oxygen uptake (VO2) were also determined. Insulin sensitivity was determined with the isoglycaemic-hyperinsulinaemic clamp technique. RESULTS: Insulin sensitivity was different (p

Ozone impacts of gas-aerosol uptake in global chemistry transport models

Science.gov (United States)

Stadtler, Scarlet; Simpson, David; Schröder, Sabine; Taraborrelli, Domenico; Bott, Andreas; Schultz, Martin

2018-03-01

The impact of six heterogeneous gas-aerosol uptake reactions on tropospheric ozone and nitrogen species was studied using two chemical transport models, the Meteorological Synthesizing Centre-West of the European Monitoring and Evaluation Programme (EMEP MSC-W) and the European Centre Hamburg general circulation model combined with versions of the Hamburg Aerosol Model and Model for Ozone and Related chemical Tracers (ECHAM-HAMMOZ). Species undergoing heterogeneous reactions in both models include N2O5, NO3, NO2, O3, HNO3, and HO2. Since heterogeneous reactions take place at the aerosol surface area, the modelled surface area density (Sa) of both models was compared to a satellite product retrieving the surface area. This comparison shows a good agreement in global pattern and especially the capability of both models to capture the extreme aerosol loadings in east Asia. The impact of the heterogeneous reactions was evaluated by the simulation of a reference run containing all heterogeneous reactions and several sensitivity runs. One reaction was turned off in each sensitivity run to compare it with the reference run. The analysis of the sensitivity runs confirms that the globally most important heterogeneous reaction is the one of N2O5. Nevertheless, NO2, HNO3, and HO2 heterogeneous reactions gain relevance particularly in east Asia due to the presence of high NOx concentrations and high Sa in the same region. The heterogeneous reaction of O3 itself on dust is of minor relevance compared to the other heterogeneous reactions. The impacts of the N2O5 reactions show strong seasonal variations, with the biggest impacts on O3 in springtime when photochemical reactions are active and N2O5 levels still high. Evaluation of the models with northern hemispheric ozone surface observations yields a better agreement of the models with observations in terms of concentration levels, variability, and temporal correlations at most sites when the heterogeneous reactions are

Nitrosative stress in human skeletal muscle attenuated by exercise countermeasure after chronic disuse.

Science.gov (United States)

Salanova, Michele; Schiffl, Gudrun; Gutsmann, Martina; Felsenberg, Dieter; Furlan, Sandra; Volpe, Pompeo; Clarke, Andrew; Blottner, Dieter

2013-01-01

Activity-induced nitric oxide (NO) imbalance and "nitrosative stress" are proposed mechanisms of disrupted Ca(2+) homeostasis in atrophic skeletal muscle. We thus mapped S-nitrosylated (SNO) functional muscle proteins in healthy male subjects in a long-term bed rest study (BBR2-2 Study) without and with exercise as countermeasure in order to assess (i) the negative effects of chronic muscle disuse by nitrosative stress, (ii) to test for possible attenuation by exercise countermeasure in bed rest and (iii) to identify new NO target proteins. Muscle biopsies from calf soleus and hip vastus lateralis were harvested at start (Pre) and at end (End) from a bed rest disuse control group (CTR, n=9) and two bed rest resistive exercise groups either without (RE, n=7) or with superimposed vibration stimuli (RVE, n=7). At subcellular compartments, strong anti-SNO-Cys immunofluorescence patterns in control muscle fibers after bed rest returned to baseline following vibration exercise. Total SNO-protein levels, Nrf-2 gene expression and nucleocytoplasmic shuttling were changed to varying degrees in all groups. Excess SNO-protein levels of specific calcium release/uptake proteins (SNO-RyR1, -SERCA1 and -PMCA) and of contractile myosin heavy chains seen in biopsy samples of chronically disused skeletal muscle were largely reduced by vibration exercise. We also identified NOS1 as a novel NO target in human skeletal muscle controlled by activity driven auto-nitrosylation mechanisms. Our findings suggest that aberrant levels of functional SNO-proteins represent signatures of uncontrolled nitrosative stress management in disused human skeletal muscle that can be offset by exercise as countermeasure.

Nitrosative stress in human skeletal muscle attenuated by exercise countermeasure after chronic disuse

Directory of Open Access Journals (Sweden)

Michele Salanova

2013-01-01

Full Text Available Activity-induced nitric oxide (NO imbalance and “nitrosative stress” are proposed mechanisms of disrupted Ca2+ homeostasis in atrophic skeletal muscle. We thus mapped S-nitrosylated (SNO functional muscle proteins in healthy male subjects in a long-term bed rest study (BBR2-2 Study without and with exercise as countermeasure in order to assess (i the negative effects of chronic muscle disuse by nitrosative stress, (ii to test for possible attenuation by exercise countermeasure in bed rest and (iii to identify new NO target proteins. Muscle biopsies from calf soleus and hip vastus lateralis were harvested at start (Pre and at end (End from a bed rest disuse control group (CTR, n=9 and two bed rest resistive exercise groups either without (RE, n=7 or with superimposed vibration stimuli (RVE, n=7. At subcellular compartments, strong anti-SNO-Cys immunofluorescence patterns in control muscle fibers after bed rest returned to baseline following vibration exercise. Total SNO-protein levels, Nrf-2 gene expression and nucleocytoplasmic shuttling were changed to varying degrees in all groups. Excess SNO-protein levels of specific calcium release/uptake proteins (SNO-RyR1, –SERCA1 and –PMCA and of contractile myosin heavy chains seen in biopsy samples of chronically disused skeletal muscle were largely reduced by vibration exercise. We also identified NOS1 as a novel NO target in human skeletal muscle controlled by activity driven auto-nitrosylation mechanisms. Our findings suggest that aberrant levels of functional SNO-proteins represent signatures of uncontrolled nitrosative stress management in disused human skeletal muscle that can be offset by exercise as countermeasure.

Comparative Study of Skeletal Stability between Postoperative Skeletal Intermaxillary Fixation and No Skeletal Fixation after Bilateral Sagittal Split Ramus Osteotomy

DEFF Research Database (Denmark)

Hartlev, Jens; Godtfredsen, Erik; Andersen, Niels Trolle

2014-01-01

OBJECTIVES: The purpose of the present study was to evaluate skeletal stability after mandibular advancement with bilateral sagittal split osteotomy. MATERIAL AND METHODS: Twenty-six patients underwent single-jaw bilateral sagittal split osteotomy (BSSO) to correct skeletal Class II malocclusion....

Effects of contraction on localization of GLUT4 and v-SNARE isoforms in rat skeletal muscle

DEFF Research Database (Denmark)

Rose, Adam John; Jeppesen, Jacob; Kiens, Bente

2009-01-01

In skeletal muscle, contractions increase glucose uptake due to a translocation of GLUT4 glucose transporters from intracellular storage sites to the surface membrane. Vesicle associated membrane proteins (VAMPs) are believed to play an important role in docking and fusion of the GLUT4 transporters...... at the surface membrane. However, knowledge about which VAMP isoforms in fact co-localize with GLUT4 vesicles in mature skeletal muscle and whether they translocate during muscle contractions is incomplete. The aim of the present study was to further identify VAMP isoforms which are associated with GLUT4......, there was a redistribution of VAMP2 (+240 +/- 40%), VAMP5 (+79 +/- 9%) and VAMP7 (+79 +/- 29%), but not VAMP3, to fractions enriched in heavy membranes away from low density membranes (-49 +/- 10%, -54 +/- 9%, -14 +/- 11%, respectively) in contracted versus resting muscle. In summary, VAMP2, VAMP3, VAMP5 and VAMP7 co...

Skeletal muscle relaxant effect of a standardized extract of Valeriana officinalis L. after acute administration in mice

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Dorian Caudal

2018-04-01

Full Text Available Valeriana officinalis L. root extracts are traditionally taken for their sedative and anxiolytic properties and are also used for muscle relaxation. Relaxant effects were clearly observed on smooth muscle whereas data on effects on skeletal muscle are scarce and inconsistent. The aim of this study was to assess whether a standardized extract (SE of V. officinalis had myorelaxant effects by decreasing skeletal muscle strength and/or neuromuscular tone in mice. Mice received an acute dose of V. officinalis SE (2 or 5 g/kg per os or tetrazepam (10 mg/kg ip, a standard myorelaxant drug. Thirty minutes later, the maximal muscle strength was measured using a grip test, while global skeletal muscle function (endurance and neuromuscular tone was assessed in a wire hanging test. Compared to tetrazepam, both doses of V. officinalis SE induced a pronounced decrease in skeletal muscle strength without any significant effects on endurance and neuromuscular tone. This study provides clear evidence that the extract of V. officinalis tested has a relaxant effect on skeletal muscle. By decreasing skeletal muscle strength without impacting endurance and neuromuscular tone, V. officinalis SE could induce less undesirable side effects than standard myorelaxant agents, and be particularly useful for avoiding falls in the elderly. Keywords: Valeriana officinalis, Skeletal muscle relaxant, Strength, Hydroethanolic root extract, Acute treatment, Mouse

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.

Diagnostic dilemma of degenerative joint disease, chronic avascular necrosis or metastasis in planar Tc-99m-methylene diphosphonate planar skeletal scintigraphy excluded by single positron emission computed tomography/computed tomography

International Nuclear Information System (INIS)

Jain, Tarun Kumar; Phulsunga, Rohit Kumar; Basher, Rajender Kumar; Kumar, Narendra; Bhattacharya, Anish; Mittal, Bhagwant Rai

2005-01-01

We present a 71-year-old male patient subjected to skeletal scintigraphy for metastasis work up of prostate cancer. Whole body planar images revealed a solitary focal tracer uptake in left femoral head mimicking as solitary metastatic focus. Single positron emission computed tomography/computed tomography images localized this increased tracer uptake to the subchondral cysts with minimal sclerosis in left femur head with no decrease in size of femur head and was reported as (degenerative joint disease)

Skeletal muscle atrophy in bioengineered skeletal muscle: a new model system.

Science.gov (United States)

Lee, Peter H U; Vandenburgh, Herman H

2013-10-01

Skeletal muscle atrophy has been well characterized in various animal models, and while certain pathways that lead to disuse atrophy and its associated functional deficits have been well studied, available drugs to counteract these deficiencies are limited. An ex vivo tissue-engineered skeletal muscle offers a unique opportunity to study skeletal muscle physiology in a controlled in vitro setting. Primary mouse myoblasts isolated from adult muscle were tissue engineered into bioartificial muscles (BAMs) containing hundreds of aligned postmitotic muscle fibers expressing sarcomeric proteins. When electrically stimulated, BAMs generated measureable active forces within 2-3 days of formation. The maximum isometric tetanic force (Po) increased for ∼3 weeks to 2587±502 μN/BAM and was maintained at this level for greater than 80 days. When BAMs were reduced in length by 25% to 50%, muscle atrophy occurred in as little as 6 days. Length reduction resulted in significant decreases in Po (50.4%), mean myofiber cross-sectional area (21.7%), total protein synthesis rate (22.0%), and noncollagenous protein content (6.9%). No significant changes occurred in either the total metabolic activity or protein degradation rates. This study is the first in vitro demonstration that length reduction alone can induce skeletal muscle atrophy, and establishes a novel in vitro model for the study of skeletal muscle atrophy.

The exercised skeletal muscle: a review

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Marina Marini

2010-09-01

Full Text Available The skeletal muscle is the second more plastic tissue of the body - second to the nervous tissue only. In fact, both physical activity and inactivity contribute to modify the skeletal muscle, by continuous signaling through nerve impulses, mechanical stimuli and humoral clues. In turn, the skeletal muscle sends signals to the body, thus contributing to its homeostasis. We'll review here the contribute of physical exercise to the shaping of skeletal muscle, to the adaptation of its mass and function to the different needs imposed by different physical activities and to the attainment of the health benefits associated with active skeletal muscles. Focus will primarily be on the molecular pathways and on gene regulation that result in skeletal muscle adaptation to exercise.

in Skeletal Muscle

Directory of Open Access Journals (Sweden)

Espen E. Spangenburg

2011-01-01

Full Text Available Triglyceride storage is altered across various chronic health conditions necessitating various techniques to visualize and quantify lipid droplets (LDs. Here, we describe the utilization of the BODIPY (493/503 dye in skeletal muscle as a means to analyze LDs. We found that the dye was a convenient and simple approach to visualize LDs in both sectioned skeletal muscle and cultured adult single fibers. Furthermore, the dye was effective in both fixed and nonfixed cells, and the staining seemed unaffected by permeabilization. We believe that the use of the BODIPY (493/503 dye is an acceptable alternative and, under certain conditions, a simpler method for visualizing LDs stored within skeletal muscle.

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

DEFF Research Database (Denmark)

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...

Single hind limb burn injury to mice alters nuclear factor-κB expression and [¹⁸F] 2-fluoro-2-deoxy-D-glucose uptake.

Science.gov (United States)

Carter, Edward A; Hamrahi, Victoria; Paul, Kasie; Bonab, Ali A; Jung, Walter; Tompkins, Ronald G; Fischman, Alan J

2014-01-01

Burn trauma to the extremities can produce marked systemic effects in mice. Burn injury to the dorsal surface of mice is also associated with changes in glucose metabolism ([18F] 2-fluoro-2-deoxy-D-glucose [18FDG] uptake) by brown adipose tissue (BAT) and nuclear factor (NF)-κB activity in several tissues including skeletal muscle. This study examined the effect of a single hind limb burn in mice on 18FDG uptake by NF-κB activity in vivo, and blood flow was determined by laser Doppler techniques. Male NF-κB luciferase reporter mice (28-30 g) were anesthetized, both legs were shaven, and the right leg was subjected to scald injury by immersion in 90°C water for 5 seconds. Sham-treated animals were used as controls. Each burned and sham mouse was resuscitated with saline (2 mL, i.p.). The individual animals were placed in wire bottom cages with no food and free access to water. After 24 hours, the animals were imaged with laser Doppler for measuring blood flow in the hind limb. The animals were then unanesthetized with 50 μCi of FDG or luciferin (1.0 mg, i.v.) via tail vein. Five minutes after luciferin injection, NF-κB mice were studied by bioluminescence imaging with a charge-coupled device camera. One hour after 18FDG injection, the animals were killed with carbon dioxide overdose, and 18FDG biodistribution was measured. Tissues were also analyzed for NF-κB luciferase activity. The scalding procedure used here produced a full-thickness burn injury to the leg with sharp margins. 18FDG uptake by the burned leg was lower than that in the contralateral limb. Similarly, luciferase activity and blood flow in the burned leg were lower than those in the contralateral leg. 18FDG uptake by BAT and heart increased, whereas that by brain decreased. In conclusion, the present study suggests that burn injury to a single leg decreased FDG uptake by skeletal muscle but increased 18FDG uptake by BAT. The injury to the leg reduced NF-κB expression compared with the

Proteomic Profiling of Mitochondrial Enzymes during Skeletal Muscle Aging

Directory of Open Access Journals (Sweden)

Lisa Staunton

2011-01-01

Full Text Available Mitochondria are of central importance for energy generation in skeletal muscles. Expression changes or functional alterations in mitochondrial enzymes play a key role during myogenesis, fibre maturation, and various neuromuscular pathologies, as well as natural fibre aging. Mass spectrometry-based proteomics suggests itself as a convenient large-scale and high-throughput approach to catalogue the mitochondrial protein complement and determine global changes during health and disease. This paper gives a brief overview of the relatively new field of mitochondrial proteomics and discusses the findings from recent proteomic surveys of mitochondrial elements in aged skeletal muscles. Changes in the abundance, biochemical activity, subcellular localization, and/or posttranslational modifications in key mitochondrial enzymes might be useful as novel biomarkers of aging. In the long term, this may advance diagnostic procedures, improve the monitoring of disease progression, help in the testing of side effects due to new drug regimes, and enhance our molecular understanding of age-related muscle degeneration.

18F-fluorodeoxyglucose accumulation in the heart, brain and skeletal muscle of rats; the influence of time after injection, depressed lipid metabolism and glucose-insulin

International Nuclear Information System (INIS)

Kasalicky, J.; Konopkova, M.; Melichar, F.

2001-01-01

To study the effect of lipid depressing drugs on 18 FDG myocardial concentration. The changes of 18 FDG uptake in myocardium, brain and skeletal muscle of rats were compared as influenced by acipimox, tyloxapol and glucose with insulin. 5.55 MBq of 18 FDG were administered to Wistar rats. Control rats were killed 15, 30, 45 and 60 minutes following intravenous injection and the radioactivity concentration (cpm/g of tissue) in relation to injected cpm was determined in a well crystal adjusted to 511 KeV in order to check the time of maximal 18 FDG tissue uptake. The radioactivity in myocardium, skeletal muscle and brain in intact animals was compared with that of rats treated with tyloxapol (tritton WR 1339, 125 mg intravenously immediately before 18 FDG injection), acipimox (nicotinic acid derivative, 25 mg by stomach cannula 15 minutes before 18 FDG), or glucose with insulin (intravenous injection of 0.04 g and 0.04 UI immediately before 18 FDG). The animals were killed 45 minutes following 18 FDG injection. Tyloxapol and acipimox significantly elevated myocardial 18 FDG concentration (tyloxapol +37% and acipimox +48%), but the increase in 18 FDG concentration after glucose and insulin was slight and insignificant. The changes in skeletal muscle after lipid depressing agents were quite contrasting; the decrease in 18 FDG concentration was -74% after tyloxapol and -44% following acipimox administration. The accumulation of 18 FDG in brain was not influenced markedly by the drugs used or by glucose with insulin. The highest 18 FDG uptake in myocardium could be achieved by depressing the lipid metabolism and not by administration of glucose with insulin only. A marked increase in glucose accumulation in myocardium is not possible without previous shift from the utilisation of fatty acids. This finding is fully in agreement with present knowledge about energetic metabolism of myocardium. (author)

Congenital anomalies and normal skeletal variants

International Nuclear Information System (INIS)

Guebert, G.M.; Yochum, T.R.; Rowe, L.J.

1987-01-01

Congenital anomalies and normal skeletal variants are a common occurrence in clinical practice. In this chapter a large number of skeletal anomalies of the spine and pelvis are reviewed. Some of the more common skeletal anomalies of the extremities are also presented. The second section of this chapter deals with normal skeletal variants. Some of these variants may simulate certain disease processes. In some instances there are no clear-cut distinctions between skeletal variants and anomalies; therefore, there may be some overlap of material. The congenital anomalies are presented initially with accompanying text, photos, and references, beginning with the skull and proceeding caudally through the spine to then include the pelvis and extremities. The normal skeletal variants section is presented in an anatomical atlas format without text or references

The Impact of Variable Phytoplankton Stoichiometry on Projections of Primary Production, Food Quality, and Carbon Uptake in the Global Ocean

Science.gov (United States)

Kwiatkowski, Lester; Aumont, Olivier; Bopp, Laurent; Ciais, Philippe

2018-04-01

Ocean biogeochemical models are integral components of Earth system models used to project the evolution of the ocean carbon sink, as well as potential changes in the physical and chemical environment of marine ecosystems. In such models the stoichiometry of phytoplankton C:N:P is typically fixed at the Redfield ratio. The observed stoichiometry of phytoplankton, however, has been shown to considerably vary from Redfield values due to plasticity in the expression of phytoplankton cell structures with different elemental compositions. The intrinsic structure of fixed C:N:P models therefore has the potential to bias projections of the marine response to climate change. We assess the importance of variable stoichiometry on 21st century projections of net primary production, food quality, and ocean carbon uptake using the recently developed Pelagic Interactions Scheme for Carbon and Ecosystem Studies Quota (PISCES-QUOTA) ocean biogeochemistry model. The model simulates variable phytoplankton C:N:P stoichiometry and was run under historical and business-as-usual scenario forcing from 1850 to 2100. PISCES-QUOTA projects similar 21st century global net primary production decline (7.7%) to current generation fixed stoichiometry models. Global phytoplankton N and P content or food quality is projected to decline by 1.2% and 6.4% over the 21st century, respectively. The largest reductions in food quality are in the oligotrophic subtropical gyres and Arctic Ocean where declines by the end of the century can exceed 20%. Using the change in the carbon export efficiency in PISCES-QUOTA, we estimate that fixed stoichiometry models may be underestimating 21st century cumulative ocean carbon uptake by 0.5-3.5% (2.0-15.1 PgC).

Sulfonylurea therapy improves glucose disposal without changing skeletal muscle GLUT4 levels in noninsulin-dependent diabetes mellitus subjects

DEFF Research Database (Denmark)

Vestergaard, H; Weinreb, J E; Rosen, A S

1995-01-01

alteration in GLUT4 levels expressed either per microgram membrane protein or per DNA. In summary, the improvement in glycemic control and glucose disposal in NIDDM subjects receiving gliclazide therapy cannot be explained by increased expression of GLUT4 in muscle. Thus, therapeutic effects on insulin......A major pathological feature of noninsulin-dependent diabetes (NIDDM) is defective insulin-stimulated glucose transport in skeletal muscle. When NIDDM subjects are assessed as a group, GLUT4 gene expression in skeletal muscle varies widely and is not different from that in controls. Thus......, longitudinal studies are needed to assess whether changes in GLUT4 expression in muscle of NIDDM subjects could be responsible for changes in glucose disposal. The question is timely because recent studies in transgenic mice show that increasing GLUT4 expression can increase insulin-stimulated glucose uptake...

Evaluation of myocardial and skeletal muscular involvement with thallium-201 myocardial emission computed tomography and whole body scintigraphy

International Nuclear Information System (INIS)

Yamamoto, Shuhei; Matsushima, Hideo; Sotobata, Iwao; Suzuki, Akio; Indo, Toshikatsu; Matsuoka, Yukihiko

1986-01-01

Thallium-201 (Tl-201) myocardial emission computed tomography and whole body scintigraphy were performed using a rotating gamma camera in 64 patients with neurologic disease and 14 normal subjects. Thallium-201 myocardial perfusion defects were seen in 40 % of the muscular involvement in 47 patients with muscular dystrophy (MD), in whom morphological abnormality of the heart was common. There was strong relationship between the degree of left ventricular perfusion defects and the degree of pulmonary uptake of Tl-201. Thallium-201 whole body scintigraphy showed homogeneous distribution of Tl-201 in the extremities in normal subjects, and perfusion defects in 73 % of the muscular lesions in MD patients. Muscular and skeletal lesions for MD appear to progress independently. Thallium-201 imaging seems to be of clinical value in assessing the muscular and skeletal lesions. (Namekawa, K.)

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...

Skeletal Stability after Large Mandibular Advancement (> 10 mm) with Bilateral Sagittal Split Osteotomy and Skeletal Elastic Intermaxillary Fixation

DEFF Research Database (Denmark)

Schwartz, Kristoffer; Rodrigo, Maria; Jensen, Thomas

2016-01-01

OBJECTIVES: The aim of the present study was to assess the skeletal stability after large mandibular advancement (> 10 mm) with bilateral sagittal split osteotomy and skeletal elastic intermaxillary fixation and to correlate the skeletal stability with the vertical facial type. MATERIAL AND METHODS......: A total of 33 consecutive patients underwent bimaxillary surgery to correct skeletal Class II malocclusion with a mandibular advancement (> 10 mm) measured at B-point and postoperative skeletal elastic intermaxillary fixation for 16 weeks. Skeletal stability was evaluated using lateral cephalometric...... radiographs obtained preoperative (T1), 8 weeks postoperatively (T2), and 18 month postoperatively (T3). B-point and pogonion (Pog) was used to measure the skeletal relapse and the mandibular plane angle (MP-angle) was used to determine the vertical facial type. RESULTS: The mean advancement from T1 to T2...

A novel PKB/Akt inhibitor, MK-2206, effectively inhibits insulin-stimulated glucose metabolism and protein synthesis in isolated rat skeletal muscle.

Science.gov (United States)

Lai, Yu-Chiang; Liu, Yang; Jacobs, Roxane; Rider, Mark H

2012-10-01

PKB (protein kinase B), also known as Akt, is a key component of insulin signalling. Defects in PKB activation lead to insulin resistance and metabolic disorders, whereas PKB overactivation has been linked to tumour growth. Small-molecule PKB inhibitors have thus been developed for cancer treatment, but also represent useful tools to probe the roles of PKB in insulin action. In the present study, we examined the acute effects of two allosteric PKB inhibitors, MK-2206 and Akti 1/2 (Akti) on PKB signalling in incubated rat soleus muscles. We also assessed the effects of the compounds on insulin-stimulated glucose uptake, glycogen and protein synthesis. MK-2206 dose-dependently inhibited insulin-stimulated PKB phosphorylation, PKBβ activity and phosphorylation of PKB downstream targets (including glycogen synthase kinase-3α/β, proline-rich Akt substrate of 40 kDa and Akt substrate of 160 kDa). Insulin-stimulated glucose uptake, glycogen synthesis and glycogen synthase activity were also decreased by MK-2206 in a dose-dependent manner. Incubation with high doses of MK-2206 (10 μM) inhibited insulin-induced p70 ribosomal protein S6 kinase and 4E-BP1 (eukaryotic initiation factor 4E-binding protein-1) phosphorylation associated with increased eEF2 (eukaryotic elongation factor 2) phosphorylation. In contrast, Akti only modestly inhibited insulin-induced PKB and mTOR (mammalian target of rapamycin) signalling, with little or no effect on glucose uptake and protein synthesis. MK-2206, rather than Akti, would thus be the tool of choice for studying the role of PKB in insulin action in skeletal muscle. The results point to a key role for PKB in mediating insulin-stimulated glucose uptake, glycogen synthesis and protein synthesis in skeletal muscle.

Benzimidazole derivative small-molecule 991 enhances AMPK activity and glucose uptake induced by AICAR or contraction in skeletal muscle.

Science.gov (United States)

Bultot, Laurent; Jensen, Thomas E; Lai, Yu-Chiang; Madsen, Agnete L B; Collodet, Caterina; Kviklyte, Samanta; Deak, Maria; Yavari, Arash; Foretz, Marc; Ghaffari, Sahar; Bellahcene, Mohamed; Ashrafian, Houman; Rider, Mark H; Richter, Erik A; Sakamoto, Kei

2016-10-01

AMP-activated protein kinase (AMPK) plays diverse roles and coordinates complex metabolic pathways for maintenance of energy homeostasis. This could be explained by the fact that AMPK exists as multiple heterotrimer complexes comprising a catalytic α-subunit (α1 and α2) and regulatory β (β1 and β2)- and γ (γ1, γ2, γ3)-subunits, which are uniquely distributed across different cell types. There has been keen interest in developing specific and isoform-selective AMPK-activating drugs for therapeutic use and also as research tools. Moreover, establishing ways of enhancing cellular AMPK activity would be beneficial for both purposes. Here, we investigated if a recently described potent AMPK activator called 991, in combination with the commonly used activator 5-aminoimidazole-4-carboxamide riboside or contraction, further enhances AMPK activity and glucose transport in mouse skeletal muscle ex vivo. Given that the γ3-subunit is exclusively expressed in skeletal muscle and has been implicated in contraction-induced glucose transport, we measured the activity of AMPKγ3 as well as ubiquitously expressed γ1-containing complexes. We initially validated the specificity of the antibodies for the assessment of isoform-specific AMPK activity using AMPK-deficient mouse models. We observed that a low dose of 991 (5 μM) stimulated a modest or negligible activity of both γ1- and γ3-containing AMPK complexes. Strikingly, dual treatment with 991 and 5-aminoimidazole-4-carboxamide riboside or 991 and contraction profoundly enhanced AMPKγ1/γ3 complex activation and glucose transport compared with any of the single treatments. The study demonstrates the utility of a dual activator approach to achieve a greater activation of AMPK and downstream physiological responses in various cell types, including skeletal muscle. Copyright © 2016 the American Physiological Society.

Bed rest reduces metabolic protein content and abolishes exercise-induced mRNA responses in human skeletal muscle

DEFF Research Database (Denmark)

Jørgensen, Stine Ringholm; Biensø, Rasmus S; Kiilerich, Kristian

2011-01-01

Background: The aim was to test the hypothesis that one week of bed rest will reduce mitochondrial number and expression and activity of oxidative proteins in human skeletal muscle, but that exercise-induced intracellular signaling as well as mRNA and microRNA (miR) responses are maintained after......-legged knee extensor exercise performed before and after bed rest. Results: Maximal oxygen uptake decreased 5% and exercise endurance decreased non-significantly 25% by bed rest. Bed rest reduced skeletal muscle mitochondrial DNA/nuclear DNA content 15%, hexokinase II and sirtuin 1 protein content ~45%, 3...... bed rest. Research Design and Methods: Twelve young, healthy, male subjects completed 7 days of bed rest with vastus lateralis muscle biopsies taken before and after bed rest. In addition, muscle biopsies were obtained from 6 of the subjects prior to, immediately after and 3h after 45 min one...

Can tumor uptake Tc-99m MDP ?

International Nuclear Information System (INIS)

Yand Shun, Fang; Yao, Ming; Zeng, Jun; Shi Zhen, Yu; Zhao Lan, Xiang; Dong Qiang, Gang

2003-01-01

tumor is higher than other part of tumor. The uptake rate of tumor is higher than non-skeletal tissue unless kidneys. It maybe connected with necrosis or calcification of tumor. Calcium and phosphorus ions were seen frequently in larger tumor. Not only it was caused by fibrous scar and/or surrounding tissues of granuloma but also intra-tumor coagulation and liquefaction necrosis (Au)

Skeletal manifestations of juvenile hypothyroidism and the impact of treatment on skeletal system.

Science.gov (United States)

Gutch, Manish; Philip, Rajeev; Philip, Renjit; Toms, Ajit; Saran, Sanjay; Gupta, K K

2013-10-01

Thyroid hormone mediates growth and development of the skeleton through its direct effects and through its permissive effects on growth hormone. The effect of hypothyroidism on bone is well described in congenital hypothyroidism, but the impact of thyroid hormone deficiency on a growing skeleton, as it happens with juvenile hypothyroidism, is less defined. In addition, the extent to which the skeletal defects of juvenile hypothyroidism revert on the replacement of thyroid hormone is not known. A study was undertaken in 29 juvenile autoimmune hypothyroid patients to study the skeletal manifestations of juvenile hypothyroidism and the impact of treatment of hypothyroidism on the skeletal system of juvenile patients. Hypothyroidism has a profound impact on the skeletal system and delayed bone age, dwarfism, and thickened bands at the metaphyseal ends being the most common findings. Post treatment, skeletal findings like delayed bone age and dwarfism improved significantly, but there were no significant changes in enlargement of sella, presence of wormian bones, epihyseal dysgenesis, vertebral changes and thickened band at the metaphyseal ends. With the treatment of hypothyroidism, there is an exuberant advancement of bone age, the catch up of bone age being approximately double of the chronological age advancement.

Expression of Gla proteins during fish skeletal development

OpenAIRE

Gavaia, Paulo J.

2006-01-01

Senegal sole skeletal development; Skeletal malformations; Skeletal malformation in mediterranean species; Senegal sole skeletal deformities; Zebra fish as model system: skeletal development; Identification of bone cells / skeletal development; Spatial - temporal pattern of bgp expression; Single cell resolution: localization of bgp mRNA; Single cell resolution: Immunolocalization of Bgp; Single cell resolution: localization of mgp mRNA; Single cell resolution: Immunolocalization of Mgp; An i...

Role of mesoscale eddies in the global ocean uptake of anthropogenic CO{sub 2}; Role des tourbillons de meso-echelle oceaniques dans la distribution et les flux air-mer de CO{sub 2} anthropique a l'echelle globale

Energy Technology Data Exchange (ETDEWEB)

Zouhair, Lachkar

2007-02-15

Mesoscale eddies play a fundamental role in ocean dynamics particularly in the Southern Ocean. Global-scale tracer simulations are typically made at coarse resolution without explicitly modeling eddies. Here we ask what role do eddies play in ocean uptake, storage, and meridional transport of anthropogenic CO{sub 2}, CFC-11 and bomb {delta}{sup 14}C. We made global anthropogenic transient tracer simulations in coarse-resolution, ORCA2, and eddy-permitting, ORCA05 and ORCA025, versions of the ocean modelling system NEMO. We focus on the Southern Ocean where tracer air-sea fluxes are largest. Eddies have little effect on bomb {delta}{sup 14}C uptake and storage. Yet for CFC-11 and anthropogenic CO{sub 2}, increased eddy activity reduces southern extra-tropical uptake by 28% and 25% respectively, thereby providing better agreement with observations. It is shown that the discrepancies in the equilibration times between the three tracers determine their respective sensitivities to the model horizontal resolution. Applying Gent and McWilliams (1990) (GM) parameterization of eddies in the non-eddying version of the model does improve results, but not enough. An in-depth investigation of the mechanisms by which eddies affect the uptake of the transient tracers shows that including mesoscale eddies leads to an overall reduction in the Antarctic Intermediate Water (AAIW) ventilation, and modifies substantially the spatial distribution of their source regions. This investigation reveals also that the GM parameterization still overestimates the ventilation and the subduction of AAIW in the Indian Ocean where the simulated mixed layer is particularly deep during the winter. This work suggests that most current coarse-resolution models may overestimate the ventilation of AAIW in the Indian sector of the Southern Ocean. This study shows also that the use of the GM parameterization may be of limited utility where mixed layer is relatively deep and confirms the general need for a

Skeletal muscle performance and ageing.

Science.gov (United States)

Tieland, Michael; Trouwborst, Inez; Clark, Brian C

2018-02-01

The world population is ageing rapidly. As society ages, the incidence of physical limitations is dramatically increasing, which reduces the quality of life and increases healthcare expenditures. In western society, ~30% of the population over 55 years is confronted with moderate or severe physical limitations. These physical limitations increase the risk of falls, institutionalization, co-morbidity, and premature death. An important cause of physical limitations is the age-related loss of skeletal muscle mass, also referred to as sarcopenia. Emerging evidence, however, clearly shows that the decline in skeletal muscle mass is not the sole contributor to the decline in physical performance. For instance, the loss of muscle strength is also a strong contributor to reduced physical performance in the elderly. In addition, there is ample data to suggest that motor coordination, excitation-contraction coupling, skeletal integrity, and other factors related to the nervous, muscular, and skeletal systems are critically important for physical performance in the elderly. To better understand the loss of skeletal muscle performance with ageing, we aim to provide a broad overview on the underlying mechanisms associated with elderly skeletal muscle performance. We start with a system level discussion and continue with a discussion on the influence of lifestyle, biological, and psychosocial factors on elderly skeletal muscle performance. Developing a broad understanding of the many factors affecting elderly skeletal muscle performance has major implications for scientists, clinicians, and health professionals who are developing therapeutic interventions aiming to enhance muscle function and/or prevent mobility and physical limitations and, as such, support healthy ageing. © 2017 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of the Society on Sarcopenia, Cachexia and Wasting Disorders.

Oncological outcomes of patients with Ewing's sarcoma: is there a difference between skeletal and extra-skeletal Ewing's sarcoma?

Science.gov (United States)

Pradhan, A; Grimer, R J; Spooner, D; Peake, D; Carter, S R; Tillman, R M; Abudu, A; Jeys, L

2011-04-01

The aim of this study was to identify whether there was any difference in patient, tumour, treatment or outcome characteristics between patients with skeletal or extra-skeletal Ewing's sarcoma. We identified 300 patients with new primary Ewing's sarcoma diagnosed between 1980 and 2005 from the centres' local database. There were 253 (84%) with skeletal and 47 (16%) with extra-skeletal Ewing's sarcomas. Although patients with skeletal Ewing's were younger (mean age 16.8 years) than those with extra-skeletal Ewing's sarcoma (mean age 27.5 years), there was little difference between the groups in terms of tumour stage or treatment. Nearly all the patients were treated with chemotherapy and most had surgery. There was no difference in the overall survival of patients with skeletal (64%) and extra-skeletal Ewing's sarcoma (61%) (p = 0.85), and this was also the case when both groups were split by whether they had metastases or not. This large series has shown that the oncological outcomes of Ewing's sarcoma are related to tumour characteristics and patient age, and not determined by whether they arise in bone or soft tissue.

Influence of Prolonged Spaceflight on Heart Rate and Oxygen Uptake Kinetics

Science.gov (United States)

Hoffmann, U.; Moore, A.; Drescher, U.

2013-02-01

During prolonged spaceflight, physical training is used to minimize cardiovascular deconditioning. Measurement of the kinetics of cardiorespiratory parameters, in particular the kinetic analysis of heart rate, respiratory and muscular oxygen uptake, provides useful information with regard to the efficiency and regulation of the cardiorespiratory system. Practically, oxygen uptake kinetics can only be measured at the lung site (V’O2 resp). The dynamics of V’O2 resp, however, is not identical with the dynamics at the site of interest: skeletal muscle. Eight Astronauts were tested pre- and post-flight using pseudo random binary workload changes between 30 and 80 W. Their kinetic responses of heart rate, respiratory as well as muscular V’O2 kinetics were estimated by using time-series analysis. Statistical analysis revealed that the kinetic responses of respiratory as well as muscular V’O2 kinetics are slowed post-flight than pre-flight. Heart rate seems not to be influenced following flight. The influence of other factors (e. g. astronauts’ exercise training) may impact these parameters and is an area for future studies.

Single Hind Limb Burn Injury to Mice Alters NF Kappa B (NF-κB) Expression and [18F] 2-Fluoro-2-Deoxy-d-Glucose (FDG) Uptake

OpenAIRE

Carter, Edward A.; Hamrahi, Victoria; Paul, Kasie; Bonab, Ali A.; Jung, Walter; Tompkins, Ronald G.; Fischman, Alan J.

2014-01-01

Burn trauma to the extremities can produce marked systemic effects in mice1, 6, 7. Burn injury to the dorsal surface of mice is also associated with changes in glucose metabolism (18FDG uptake) by brown adipose tissue (BAT) and NF-κB activity in a number of tissues including skeletal muscle. This study examined the effect of a single hindlimb burn in mice on 18FDG uptake by in vivo, NF-κB activity in vivo, and blood flow determined by laser Doppler techniques. Male mice NF-κB luciferase repor...

Skeletal muscle neuronal nitric oxide synthase micro protein is reduced in people with impaired glucose homeostasis and is not normalized by exercise training.

Science.gov (United States)

Bradley, Scott J; Kingwell, Bronwyn A; Canny, Benedict J; McConell, Glenn K

2007-10-01

Skeletal muscle inducible nitric oxide synthase (NOS) protein is greatly elevated in people with type 2 diabetes mellitus, whereas endothelial NOS is at normal levels. Diabetic rat studies suggest that skeletal muscle neuronal NOS (nNOS) micro protein expression may be reduced in human insulin resistance. The aim of this study was to determine whether skeletal muscle nNOSmicro protein expression is reduced in people with impaired glucose homeostasis and whether exercise training increases nNOSmicro protein expression in these individuals because exercise training increases skeletal muscle nNOSmicro protein in rats. Seven people with type 2 diabetes mellitus or prediabetes (impaired fasting glucose and/or impaired glucose tolerance) and 7 matched (sex, age, fitness, body mass index, blood pressure, lipid profile) healthy controls aged 36 to 60 years participated in this study. Vastus lateralis muscle biopsies for nNOSmicro protein determination were obtained, aerobic fitness was measured (peak pulmonary oxygen uptake [Vo(2) peak]), and glucose tolerance and insulin homeostasis were assessed before and after 1 and 4 weeks of cycling exercise training (60% Vo(2) peak, 50 minutes x 5 d wk(-1)). Skeletal muscle nNOSmicro protein was significantly lower (by 32%) in subjects with type 2 diabetes mellitus or prediabetes compared with that in controls before training (17.7 +/- 1.2 vs 26.2 +/- 3.4 arbitrary units, P glucose homeostasis have reduced skeletal muscle nNOSmicro protein content. However, because exercise training improves insulin sensitivity without influencing skeletal muscle nNOSmicro protein expression, it seems that changes in skeletal muscle nNOSmicro protein are not central to the control of insulin sensitivity in humans and therefore may be a consequence rather than a cause of diabetes.

Skeletal manifestations of juvenile hypothyroidism and the impact of treatment on skeletal system

Directory of Open Access Journals (Sweden)

Manish Gutch

2013-01-01

Full Text Available Thyroid hormone mediates growth and development of the skeleton through its direct effects and through its permissive effects on growth hormone. The effect of hypothyroidism on bone is well described in congenital hypothyroidism, but the impact of thyroid hormone deficiency on a growing skeleton, as it happens with juvenile hypothyroidism, is less defined. In addition, the extent to which the skeletal defects of juvenile hypothyroidism revert on the replacement of thyroid hormone is not known. A study was undertaken in 29 juvenile autoimmune hypothyroid patients to study the skeletal manifestations of juvenile hypothyroidism and the impact of treatment of hypothyroidism on the skeletal system of juvenile patients. Hypothyroidism has a profound impact on the skeletal system and delayed bone age, dwarfism, and thickened bands at the metaphyseal ends being the most common findings. Post treatment, skeletal findings like delayed bone age and dwarfism improved significantly, but there were no significant changes in enlargement of sella, presence of wormian bones, epihyseal dysgenesis, vertebral changes and thickened band at the metaphyseal ends. With the treatment of hypothyroidism, there is an exuberant advancement of bone age, the catch up of bone age being approximately double of the chronological age advancement.

Skeletal muscle and fetal alcohol spectrum disorder.

Science.gov (United States)

Myrie, Semone B; Pinder, Mark A

2018-04-01

Skeletal muscle is critical for mobility and many metabolic functions integral to survival and long-term health. Alcohol can affect skeletal muscle physiology and metabolism, which will have immediate and long-term consequences on health. While skeletal muscle abnormalities, including morphological, biochemical, and functional impairments, are well-documented in adults that excessively consume alcohol, there is a scarcity of information about the skeletal muscle in the offspring prenatally exposed to alcohol ("prenatal alcohol exposure"; PAE). This minireview examines the available studies addressing skeletal muscle abnormalities due to PAE. Growth restriction, fetal alcohol myopathy, and abnormalities in the neuromuscular system, which contribute to deficits in locomotion, are some direct, immediate consequences of PAE on skeletal muscle morphology and function. Long-term health consequences of PAE-related skeletal abnormalities include impaired glucose metabolism in the skeletal muscle, resulting in glucose intolerance and insulin resistance, leading to an increased risk of type 2 diabetes. In general, there is limited information on the morphological, biochemical, and functional features of skeletal abnormalities in PAE offspring. There is a need to understand how PAE affects muscle growth and function at the cellular level during early development to improve the immediate and long-term health of offspring suffering from PAE.

New diphosphonate compounds for skeletal imaging: comparison with methylene diphosphonate

International Nuclear Information System (INIS)

Subramanian, G.; McAfee, J.G.; Thomas, F.D.; Feld, T.A.; Zapf-Longo, C.; Palladino, E.

1983-01-01

Three-hour biodistribution of Tc-99m complexes of six diphosphonates was compared in rabbits with tibial lesions to determine which was best for detection of focal bone lesions. Sr-85 was used as a standard. N,N-dimethylaminomethylene diphosphonate (DMAD) was the only agent with a higher lesion/normal bone ratio than methylene diphosphonate (MDP), attributable to lower concentration in normal bone. Hydroxymethane diphosphonate (HDP) and 2,3-dicarboxypropane-1, 1-diphosphonate (DPD) demonstrated higher concentration than MDP in normal bone without improving lesion contrast. They also exhibited much higher uptake in the liver and kidney, as well as muscle and red marrow in the case of DPD. None was superior to MDP as an all-purpose skeletal agent, though others may be better for specific applications

Augmentation of aerobic respiration and mitochondrial biogenesis in skeletal muscle by hypoxia preconditioning with cobalt chloride

Energy Technology Data Exchange (ETDEWEB)

Saxena, Saurabh [Experimental Biology Division, Defence Institute of Physiology and Allied Sciences, Lucknow Road, Timarpur, Delhi, 110054 (India); Shukla, Dhananjay [Department of Biotechnology, Gitam University, Gandhi Nagar, Rushikonda, Visakhapatnam-530 045 Andhra Pradesh (India); Bansal, Anju, E-mail: anjubansaldipas@gmail.com [Experimental Biology Division, Defence Institute of Physiology and Allied Sciences, Lucknow Road, Timarpur, Delhi, 110054 (India)

2012-11-01

High altitude/hypoxia training is known to improve physical performance in athletes. Hypoxia induces hypoxia inducible factor-1 (HIF-1) and its downstream genes that facilitate hypoxia adaptation in muscle to increase physical performance. Cobalt chloride (CoCl{sub 2}), a hypoxia mimetic, stabilizes HIF-1, which otherwise is degraded in normoxic conditions. We studied the effects of hypoxia preconditioning by CoCl{sub 2} supplementation on physical performance, glucose metabolism, and mitochondrial biogenesis using rodent model. The results showed significant increase in physical performance in cobalt supplemented rats without (two times) or with training (3.3 times) as compared to control animals. CoCl{sub 2} supplementation in rats augmented the biological activities of enzymes of TCA cycle, glycolysis and cytochrome c oxidase (COX); and increased the expression of glucose transporter-1 (Glut-1) in muscle showing increased glucose metabolism by aerobic respiration. There was also an increase in mitochondrial biogenesis in skeletal muscle observed by increased mRNA expressions of mitochondrial biogenesis markers which was further confirmed by electron microscopy. Moreover, nitric oxide production increased in skeletal muscle in cobalt supplemented rats, which seems to be the major reason for peroxisome proliferator activated receptor-gamma coactivator-1α (PGC-1α) induction and mitochondrial biogenesis. Thus, in conclusion, we state that hypoxia preconditioning by CoCl{sub 2} supplementation in rats increases mitochondrial biogenesis, glucose uptake and metabolism by aerobic respiration in skeletal muscle, which leads to increased physical performance. The significance of this study lies in understanding the molecular mechanism of hypoxia adaptation and improvement of work performance in normal as well as extreme conditions like hypoxia via hypoxia preconditioning. -- Highlights: ► We supplemented rats with CoCl{sub 2} for 15 days along with training. ► Co

Augmentation of aerobic respiration and mitochondrial biogenesis in skeletal muscle by hypoxia preconditioning with cobalt chloride

International Nuclear Information System (INIS)

Saxena, Saurabh; Shukla, Dhananjay; Bansal, Anju

2012-01-01

High altitude/hypoxia training is known to improve physical performance in athletes. Hypoxia induces hypoxia inducible factor-1 (HIF-1) and its downstream genes that facilitate hypoxia adaptation in muscle to increase physical performance. Cobalt chloride (CoCl 2 ), a hypoxia mimetic, stabilizes HIF-1, which otherwise is degraded in normoxic conditions. We studied the effects of hypoxia preconditioning by CoCl 2 supplementation on physical performance, glucose metabolism, and mitochondrial biogenesis using rodent model. The results showed significant increase in physical performance in cobalt supplemented rats without (two times) or with training (3.3 times) as compared to control animals. CoCl 2 supplementation in rats augmented the biological activities of enzymes of TCA cycle, glycolysis and cytochrome c oxidase (COX); and increased the expression of glucose transporter-1 (Glut-1) in muscle showing increased glucose metabolism by aerobic respiration. There was also an increase in mitochondrial biogenesis in skeletal muscle observed by increased mRNA expressions of mitochondrial biogenesis markers which was further confirmed by electron microscopy. Moreover, nitric oxide production increased in skeletal muscle in cobalt supplemented rats, which seems to be the major reason for peroxisome proliferator activated receptor-gamma coactivator-1α (PGC-1α) induction and mitochondrial biogenesis. Thus, in conclusion, we state that hypoxia preconditioning by CoCl 2 supplementation in rats increases mitochondrial biogenesis, glucose uptake and metabolism by aerobic respiration in skeletal muscle, which leads to increased physical performance. The significance of this study lies in understanding the molecular mechanism of hypoxia adaptation and improvement of work performance in normal as well as extreme conditions like hypoxia via hypoxia preconditioning. -- Highlights: ► We supplemented rats with CoCl 2 for 15 days along with training. ► CoCl 2 supplementation

Revelation of the Sun Self-Similarity Skeletal Structures

International Nuclear Information System (INIS)

Rantsev-Kartinov, V.A.

2005-01-01

The analysis of databases of photographic images of a surface of the Sun, its atmosphere and the closest its space environment taken at various spatial resolutions and for various types of radiation of a surface of the Sun by means of a method multilevel dynamic contrasting, has revealed presence skeletal structures as on the Sun directly such and in its environment. It is demonstrated the revealed a global structures of the Sun and powerful ejections of mass of its corona, as well as the structures of its atmosphere, protuberances, sun-spots and a globular structures of its photosphere

MASTR directs MyoD-dependent satellite cell differentiation during skeletal muscle regeneration

Science.gov (United States)

Mokalled, Mayssa H.; Johnson, Aaron N.; Creemers, Esther E.; Olson, Eric N.

2012-01-01

In response to skeletal muscle injury, satellite cells, which function as a myogenic stem cell population, become activated, expand through proliferation, and ultimately fuse with each other and with damaged myofibers to promote muscle regeneration. Here, we show that members of the Myocardin family of transcriptional coactivators, MASTR and MRTF-A, are up-regulated in satellite cells in response to skeletal muscle injury and muscular dystrophy. Global and satellite cell-specific deletion of MASTR in mice impairs skeletal muscle regeneration. This impairment is substantially greater when MRTF-A is also deleted and is due to aberrant differentiation and excessive proliferation of satellite cells. These abnormalities mimic those associated with genetic deletion of MyoD, a master regulator of myogenesis, which is down-regulated in the absence of MASTR and MRTF-A. Consistent with an essential role of MASTR in transcriptional regulation of MyoD expression, MASTR activates a muscle-specific postnatal MyoD enhancer through associations with MEF2 and members of the Myocardin family. Our results provide new insights into the genetic circuitry of muscle regeneration and identify MASTR as a central regulator of this process. PMID:22279050

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.

A contemporary Colombian skeletal reference collection: A resource for the development of population specific standards.

Science.gov (United States)

Sanabria-Medina, Cesar; González-Colmenares, Gretel; Restrepo, Hadaluz Osorio; Rodríguez, Juan Manuel Guerrero

2016-09-01

Several authors who have discussed human variability and its impact on the forensic identification of bodies pose the need for regional studies documenting the global variation of the attributes analyzed osteological characteristics that aid in establishing biological profile (sex, ancestry, biological age and height). This is primarily accomplished by studying documented human skeletal collections in order to investigate secular trends in skeletal development and aging, among others in the Colombian population. The purpose of this paper is to disclose the details of the new "Contemporary Colombian Skeletal Reference Collection" that currently comprises 600 identified skeletons of both sexes, who died between 2005 and 2008; and which contain information about their cause of death. This collection has infinite potential for research, open to the national and international community, and still has pending opportunities to address a variety of topics such as studies on osteopathology, bone trauma and taphonomic studies. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Effect of L-carnitine supplementation on the body carnitine pool, skeletal muscle energy metabolism and physical performance in male vegetarians.

Science.gov (United States)

Novakova, Katerina; Kummer, Oliver; Bouitbir, Jamal; Stoffel, Sonja D; Hoerler-Koerner, Ulrike; Bodmer, Michael; Roberts, Paul; Urwyler, Albert; Ehrsam, Rolf; Krähenbühl, Stephan

2016-02-01

More than 95% of the body carnitine is located in skeletal muscle, where it is essential for energy metabolism. Vegetarians ingest less carnitine and carnitine precursors and have lower plasma carnitine concentrations than omnivores. Principle aims of the current study were to assess the plasma and skeletal muscle carnitine content and physical performance of male vegetarians and matched omnivores under basal conditions and after L-carnitine supplementation. Sixteen vegetarians and eight omnivores participated in this interventional study with oral supplementation of 2 g L-carnitine for 12 weeks. Before carnitine supplementation, vegetarians had a 10% lower plasma carnitine concentration, but maintained skeletal muscle carnitine stores compared to omnivores. Skeletal muscle phosphocreatine, ATP, glycogen and lactate contents were also not different from omnivores. Maximal oxygen uptake (VO2max) and workload (P max) per bodyweight (bicycle spiroergometry) were not significantly different between vegetarians and omnivores. Sub-maximal exercise (75% VO2max for 1 h) revealed no significant differences between vegetarians and omnivores (respiratory exchange ratio, blood lactate and muscle metabolites). Supplementation with L-carnitine significantly increased the total plasma carnitine concentration (24% in omnivores, 31% in vegetarians) and the muscle carnitine content in vegetarians (13%). Despite this increase, P max and VO2max as well as muscle phosphocreatine, lactate and glycogen were not significantly affected by carnitine administration. Vegetarians have lower plasma carnitine concentrations, but maintained muscle carnitine stores compared to omnivores. Oral L-carnitine supplementation normalizes the plasma carnitine stores and slightly increases the skeletal muscle carnitine content in vegetarians, but without affecting muscle function and energy metabolism.

Human skeletal muscle releases leptin in vivo

DEFF Research Database (Denmark)

Wolsk, Emil; Grøndahl, Thomas Sahl; Pedersen, Bente Klarlund

2012-01-01

Leptin is considered an adipokine, however, cultured myocytes have also been found to release leptin. Therefore, as proof-of-concept we investigated if human skeletal muscle synthesized leptin by measuring leptin in skeletal muscle biopsies. Following this, we quantified human skeletal muscle...... was unaltered. During saline infusion the adipose tissue release averaged 0.8 ± 0.3 ng min(-1) 100g tissue(-1) whereas skeletal muscle release was 0.5 ± 0.1 ng min(-1) 100g tissue(-1). In young healthy humans, skeletal muscle contribution to whole body leptin production could be substantial given the greater...

Constraining global methane emissions and uptake by ecosystems

International Nuclear Information System (INIS)

Spahni, R.; Wania, R.; Neef, L.; Van Weele, M.; Van Velthoven, P.; Pison, I.; Bousquet, P.

2011-01-01

Natural methane (CH 4 ) emissions from wet ecosystems are an important part of today's global CH 4 budget. Climate affects the exchange of CH 4 between ecosystems and the atmosphere by influencing CH 4 production, oxidation, and transport in the soil. The net CH 4 exchange depends on ecosystem hydrology, soil and vegetation characteristics. Here, the LPJ-WHyMe global dynamical vegetation model is used to simulate global net CH 4 emissions for different ecosystems: northern peat-lands (45 degrees-90 degrees N), naturally inundated wetlands (60 degrees S-45 degrees N), rice agriculture and wet mineral soils. Mineral soils are a potential CH 4 sink, but can also be a source with the direction of the net exchange depending on soil moisture content. The geographical and seasonal distributions are evaluated against multi-dimensional atmospheric inversions for 2003-2005, using two independent four-dimensional variational assimilation systems. The atmospheric inversions are constrained by the atmospheric CH 4 observations of the SCIAMACHY satellite instrument and global surface networks. Compared to LPJ-WHyMe the inversions result in a significant reduction in the emissions from northern peat-lands and suggest that LPJ-WHyMe maximum annual emissions peak about one month late. The inversions do not put strong constraints on the division of sources between inundated wetlands and wet mineral soils in the tropics. Based on the inversion results we diagnose model parameters in LPJ-WHyMe and simulate the surface exchange of CH 4 over the period 1990-2008. Over the whole period we infer an increase of global ecosystem CH 4 emissions of +1.11 TgCH 4 yr -1 , not considering potential additional changes in wetland extent. The increase in simulated CH 4 emissions is attributed to enhanced soil respiration resulting from the observed rise in land temperature and in atmospheric carbon dioxide that were used as input. The long term decline of the atmospheric CH 4 growth rate from 1990

Surge ammonium uptake in macroalgae from a coral atoll

Digital Repository Service at National Institute of Oceanography (India)

Raikar, V.; Wafar, M.V.M.

of Phycology 36, 680?685. Crossland, C.J., Hatcher, B.G., Smith, S.V., 1991. Role of coral reefs in global ocean production. Coral Reefs 10, 55-64. Danilo, Dy. T., Yap, H.T., 2001. Surge ammonium uptake of the cultured seaweed, Kappaphycus alvarezii (Doty...

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

Science.gov (United States)

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.

Technetium-99m sestamibi leg scintigraphy for non-invasive assessment of propionyl-l-carnitine induced changes in skeletal muscle metabolism

Energy Technology Data Exchange (ETDEWEB)

Cittanti, C. [Department of Nuclear Medicine, University of Ferrara (Italy); Colamussi, P. [Department of Nuclear Medicine, University of Ferrara (Italy); Giganti, M. [Department of Nuclear Medicine, University of Ferrara (Italy); Orlandi, C. [MEDCO Research, Inc., North Carolina (United States); Uccelli, L. [Department of Nuclear Medicine, University of Ferrara (Italy); Manfrini, S. [Surgical Pathology Institute, University of Ferrara (Italy); Azzena, G. [Surgical Pathology Institute, University of Ferrara (Italy); Piffanelli, A. [Department of Nuclear Medicine, University of Ferrara (Italy)

1997-07-01

Carnitine derivatives, such as propionyl-l-carnitine (PLC), have been shown to improve walking distance in patients with obstructive peripheral artery disease (PAOD). The aim of this study was to ascertain whether technetium-99m sestamibi leg scintigraphy may be a useful tool in the evaluation of changes in skeletal muscle metabolism induced by chronic therapy with PLC. Twenty patients with clinical and instrumental evidence of PAOD were randomly assigned to a 3-month period of therapy with either PLC or placebo. Rest {sup 99m}Tc-sestamibi leg scintigraphy and echo-Doppler sonography were performed on all subjects immediately before and upon completion of the treatment period. At the end of the protocol the following results were observed in patients who underwent PLC administration: (a) a significant increase in both thigh and calf {sup 99m}Tc-sestamibi uptake, in comparison with baseline values (P<0.001); (b) the absence of statistically significant modifications of Doppler blood flow indices of the lower limbs. In conclusion, after chronic administration of PLC, a significant increment in skeletal muscle uptake of {sup 99m}Tc-sestamibi was demonstrated without any apparent change in regional blood flow. This fact, if proven in further studies, may suggest a role for this tracer as a non-invasive probe of tissue bioenergetics. (orig.). With 4 figs., 4 tabs.

Skeletal Muscle Na+ Channel Disorders

Directory of Open Access Journals (Sweden)

Dina eSimkin

2011-10-01

Full Text Available Five inherited human disorders affecting skeletal muscle contraction have been traced to mutations in the gene encoding the voltage-gated sodium channel Nav1.4. The main symptoms of these disorders are myotonia or periodic paralysis caused by changes in skeletal muscle fiber excitability. Symptoms of these disorders vary from mild or latent disease to incapacitating or even death in severe cases. As new human sodium channel mutations corresponding to disease states become discovered, the importance of understanding the role of the sodium channel in skeletal muscle function and disease state grows.

Extracellular matrix adaptation of tendon and skeletal muscle to exercise

DEFF Research Database (Denmark)

Kjaer, Michael; Magnusson, Peter; Krogsgaard, Michael

2006-01-01

The extracellular matrix (ECM) of connective tissues enables linking to other tissues, and plays a key role in force transmission and tissue structure maintenance in tendons, ligaments, bone and muscle. ECM turnover is influenced by physical activity, and both collagen synthesis and metalloprotease......-beta and IL-6 is enhanced following exercise. For tendons, metabolic activity (e.g. detected by positron emission tomography scanning), circulatory responses (e.g. as measured by near-infrared spectroscopy and dye dilution) and collagen turnover are markedly increased after exercise. Tendon blood flow...... is regulated by cyclooxygenase-2 (COX-2)-mediated pathways, and glucose uptake is regulated by specific pathways in tendons that differ from those in skeletal muscle. Chronic loading in the form of physical training leads both to increased collagen turnover as well as to some degree of net collagen synthesis...

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

Science.gov (United States)

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.

Redox Control of Skeletal Muscle Regeneration.

Science.gov (United States)

Le Moal, Emmeran; Pialoux, Vincent; Juban, Gaëtan; Groussard, Carole; Zouhal, Hassane; Chazaud, Bénédicte; Mounier, Rémi

2017-08-10

Skeletal muscle shows high plasticity in response to external demand. Moreover, adult skeletal muscle is capable of complete regeneration after injury, due to the properties of muscle stem cells (MuSCs), the satellite cells, which follow a tightly regulated myogenic program to generate both new myofibers and new MuSCs for further needs. Although reactive oxygen species (ROS) and reactive nitrogen species (RNS) have long been associated with skeletal muscle physiology, their implication in the cell and molecular processes at work during muscle regeneration is more recent. This review focuses on redox regulation during skeletal muscle regeneration. An overview of the basics of ROS/RNS and antioxidant chemistry and biology occurring in skeletal muscle is first provided. Then, the comprehensive knowledge on redox regulation of MuSCs and their surrounding cell partners (macrophages, endothelial cells) during skeletal muscle regeneration is presented in normal muscle and in specific physiological (exercise-induced muscle damage, aging) and pathological (muscular dystrophies) contexts. Recent advances in the comprehension of these processes has led to the development of therapeutic assays using antioxidant supplementation, which result in inconsistent efficiency, underlying the need for new tools that are aimed at precisely deciphering and targeting ROS networks. This review should provide an overall insight of the redox regulation of skeletal muscle regeneration while highlighting the limits of the use of nonspecific antioxidants to improve muscle function. Antioxid. Redox Signal. 27, 276-310.

Uptake of post‑abortion contraception among women who had ...

African Journals Online (AJOL)

Background: Unexpected or unplanned pregnancy poses a major public health challenge in women of reproductive age, especially in low resource countries. Post‑abortion contraception is one of the key methods of reducing maternal mortality globally. Objectives: This study was conducted to determine the uptake of ...

Global Land Carbon Uptake from Trait Distributions

Science.gov (United States)

Butler, E. E.; Datta, A.; Flores-Moreno, H.; Fazayeli, F.; Chen, M.; Wythers, K. R.; Banerjee, A.; Atkin, O. K.; Kattge, J.; Reich, P. B.

2016-12-01

Historically, functional diversity in land surface models has been represented through a range of plant functional types (PFTs), each of which has a single value for all of its functional traits. Here we expand the diversity of the land surface by using a distribution of trait values for each PFT. The data for these trait distributions is from a sub-set of the global database of plant traits, TRY, and this analysis uses three leaf traits: mass based nitrogen and phosphorus content and specific leaf area, which influence both photosynthesis and respiration. The data are extrapolated into continuous surfaces through two methodologies. The first, a categorical method, classifies the species observed in TRY into satellite estimates of their plant functional type abundances - analogous to how traits are currently assigned to PFTs in land surface models. Second, a Bayesian spatial method which additionally estimates how the distribution of a trait changes in accord with both climate and soil covariates. These two methods produce distinct patterns of diversity which are incorporated into a land surface model to estimate how the range of trait values affects the global land carbon budget.

Cerebellar medulloblastoma presenting with skeletal metastasis

Directory of Open Access Journals (Sweden)

Barai Sukanta

2004-04-01

Full Text Available Medulloblastomas are highly malignant brain tumours, but only rarely produce skeletal metastases. No case of medulloblastoma has been documented to have produced skeletal metastases prior to craniotomy or shunt surgery. A 21-year-old male presented with pain in the hip and lower back with difficulty in walking of 3 months′ duration. Signs of cerebellar dysfunction were present hence a diagnosis of cerebellar neoplasm or skeletal tuberculosis with cerebellar abscess formation was considered. MRI of brain revealed a lesion in the cerebellum suggestive of medulloblastoma. Bone scan revealed multiple sites of skeletal metastases excluding the lumbar vertebrae. MRI of lumbar spine and hip revealed metastases to all lumbar vertebrae and both hips. Computed tomography-guided biopsy was obtained from the L3 vertebra, which revealed metastatic deposits from medulloblastoma. Cerebrospinal fluid cytology showed the presence of medulloblastoma cells. A final diagnosis of cerebellar medulloblastoma with skeletal metastases was made. He underwent craniotomy and histopathology confirmed medulloblastoma.

microRNA-320/RUNX2 axis regulates adipocytic differentiation of human mesenchymal (skeletal) stem cells

DEFF Research Database (Denmark)

Hamam, D; Ali, D; Vishnubalaji, R

2014-01-01

The molecular mechanisms promoting lineage-specific commitment of human mesenchymal (skeletal or stromal) stem cells (hMSCs) into adipocytes (ADs) are not fully understood. Thus, we performed global microRNA (miRNA) and gene expression profiling during adipocytic differentiation of h...... differentiation and accelerated formation of mature ADs in ex vivo cultures. Integrated analysis of bioinformatics and global gene expression profiling in miR-320c overexpressing cells and during adipocytic differentiation of hMSC identified several biologically relevant gene targets for miR-320c including RUNX2...

Composition and biosynthesis of lipids in the healthy human skeletal muscle

International Nuclear Information System (INIS)

Schlenska, K.

1979-01-01

The skeletal muscle samples were ground in a Warburg Apparatus under oxygen, incubated for 20 to 120 min. at 37 0 C together with the three precursors of lipid biosynthesis, and oxygen uptake and 14 Co 2 -formation measured. Both parameters showed increasing values during the incubation time. The total lipid extract was isolated from the labelled skeletal muscle samples and was separated, following chromatographic purification on Sephatex-G 25 with the aid of thin-layer chromatography on silica gel, into the following fractions in order of decreasing concentration: phospholipids, triglycerides, cholesterol, mono- and diglyceride fraction, cholesterol ester fraction. Following in-vitro labelling with the three precursors, of the phospholipid fraction [ 3 H] palmilic and showed the highest, increasing incorporation rate, and [ 14 C] acetate the lowest level and slow rate of incorporation. For the central fat fraction labelling incorporation rate decreased in the order: monoglycerides > diglycerides > triglycerides. [ 14 C] acetate labelling occurred to a greater extent in cholestorol esters than in the cholestorol fraction. These findings indicate a de-novo biosynthesis of fatty acids from acetate and their incorporation in mono-, di-and triglycerides and in cholesterol ester. Moreover, incorporation of palmitic and in these fractions, de-novo synthesis of cholesterol, and incorporation of PO 4 3 - and labelled fatty acids in the phospholipid fraction are also suggested. (orig./MG) [de

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...

Unusual metabolic characteristics in skeletal muscles of transgenic rabbits for human lipoprotein lipase

Directory of Open Access Journals (Sweden)

Viglietta Céline

2004-12-01

Full Text Available Abstract Background The lipoprotein lipase (LPL hydrolyses circulating triacylglycerol-rich lipoproteins. Thereby, LPL acts as a metabolic gate-keeper for fatty acids partitioning between adipose tissue for storage and skeletal muscle primarily for energy use. Transgenic mice that markedly over-express LPL exclusively in muscle, show increases not only in LPL activity, but also in oxidative enzyme activities and in number of mitochondria, together with an impaired glucose tolerance. However, the role of LPL in intracellular nutrient pathways remains uncertain. To examine differences in muscle nutrient uptake and fatty acid oxidative pattern, transgenic rabbits harboring a DNA fragment of the human LPL gene (hLPL and their wild-type littermates were compared for two muscles of different metabolic type, and for perirenal fat. Results Analyses of skeletal muscles and adipose tissue showed the expression of the hLPL DNA fragment in tissues of the hLPL group only. Unexpectedly, the activity level of LPL in both tissues was similar in the two groups. Nevertheless, mitochondrial fatty acid oxidation rate, measured ex vivo using [1-14C]oleate as substrate, was lower in hLPL rabbits than in wild-type rabbits for the two muscles under study. Both insulin-sensitive glucose transporter GLUT4 and muscle fatty acid binding protein (H-FABP contents were higher in hLPL rabbits than in wild-type littermates for the pure oxidative semimembranosus proprius muscle, but differences between groups did not reach significance when considering the fast-twitch glycolytic longissimus muscle. Variations in both glucose uptake potential, intra-cytoplasmic binding of fatty acids, and lipid oxidation rate observed in hLPL rabbits compared with their wild-type littermates, were not followed by any modifications in tissue lipid content, body fat, and plasma levels in energy-yielding metabolites. Conclusions Expression of intracellular binding proteins for both fatty acids and

Simple physics-based models of compensatory plant water uptake: concepts and eco-hydrological consequences

Directory of Open Access Journals (Sweden)

N. J. Jarvis

2011-11-01

Full Text Available Many land surface schemes and simulation models of plant growth designed for practical use employ simple empirical sub-models of root water uptake that cannot adequately reflect the critical role water uptake from sparsely rooted deep subsoil plays in meeting atmospheric transpiration demand in water-limited environments, especially in the presence of shallow groundwater. A failure to account for this so-called "compensatory" water uptake may have serious consequences for both local and global modeling of water and energy fluxes, carbon balances and climate. Some purely empirical compensatory root water uptake models have been proposed, but they are of limited use in global modeling exercises since their parameters cannot be related to measurable soil and vegetation properties. A parsimonious physics-based model of uptake compensation has been developed that requires no more parameters than empirical approaches. This model is described and some aspects of its behavior are illustrated with the help of example simulations. These analyses demonstrate that hydraulic lift can be considered as an extreme form of compensation and that the degree of compensation is principally a function of soil capillarity and the ratio of total effective root length to potential transpiration. Thus, uptake compensation increases as root to leaf area ratios increase, since potential transpiration depends on leaf area. Results of "scenario" simulations for two case studies, one at the local scale (riparian vegetation growing above shallow water tables in seasonally dry or arid climates and one at a global scale (water balances across an aridity gradient in the continental USA, are presented to illustrate biases in model predictions that arise when water uptake compensation is neglected. In the first case, it is shown that only a compensated model can match the strong relationships between water table depth and leaf area and transpiration observed in riparian forest

Spot light on skeletal muscles: optogenetic stimulation to understand and restore skeletal muscle function.

Science.gov (United States)

van Bremen, Tobias; Send, Thorsten; Sasse, Philipp; Bruegmann, Tobias

2017-08-01

Damage of peripheral nerves results in paralysis of skeletal muscle. Currently, the only treatment option to restore proper function is electrical stimulation of the innervating nerve or of the skeletal muscles directly. However this approach has low spatial and temporal precision leading to co-activation of antagonistic muscles and lacks cell-type selectivity resulting in pain or discomfort by stimulation of sensible nerves. In contrast to electrical stimulation, optogenetic methods enable spatially confined and cell-type selective stimulation of cells expressing the light sensitive channel Channelrhodopsin-2 with precise temporal control over the membrane potential. Herein we summarize the current knowledge about the use of this technology to control skeletal muscle function with the focus on the direct, non-neuronal stimulation of muscle fibers. The high temporal flexibility of using light pulses allows new stimulation patterns to investigate skeletal muscle physiology. Furthermore, the high spatial precision of focused illumination was shown to be beneficial for selective stimulation of distinct nearby muscle groups. Finally, the cell-type specific expression of the light-sensitive effector proteins in muscle fibers will allow pain-free stimulation and open new options for clinical treatments. Therefore, we believe that direct optogenetic stimulation of skeletal muscles is a very potent method for basic scientists that also harbors several distinct advantages over electrical stimulation to be considered for clinical use in the future.

Activation-induced resetting of cerebral oxygen and glucose uptake in the rat

DEFF Research Database (Denmark)

Madsen, P L; Linde, R; Hasselbalch, S G

1998-01-01

In the clinical setting it has been shown that activation will increase cerebral glucose uptake in excess of cerebral oxygen uptake. To study this phenomenon further, this study presents an experimental setup that enables precise determination of the ratio between cerebral uptake of glucose...... and oxygen in the awake rat. Global CBF was measured by the Kety-Schmidt technique, and the ratio between cerebral uptake rates for oxygen, glucose, and lactate was calculated from cerebral arterial-venous differences. During baseline conditions, rats were kept in a closed box designed to minimize...... interference. During baseline conditions CBF was 1.08 +/- 0.25 mL x g(-1) x minute(-1), and the cerebral oxygen to glucose uptake ratio was 5.5. Activation was induced by opening the sheltering box for 6 minutes. Activation increased CBF to 1.81 mL x g(-1) x minute(-1). During activation cerebral glucose...

Skeletal dosimetry models for alpha-particles for use in molecular radiotherapy

Science.gov (United States)

Watchman, Christopher J.

Molecular radiotherapy is a cancer treatment methodology whereby a radionuclide is combined with a biologically active molecule to preferentially target cancer cells. Alpha-particle emitting radionuclides show significant potential for use in molecular radiotherapy due to the short range of the alpha-particles in tissue and their high rates of energy deposition. Current radiation dosimetry models used to assess alpha emitter dose in the skeleton were developed originally for occupational applications. In medical dosimetry, individual variability in uptake, translocation and other biological factors can result in poor correlation of clinical outcome with marrow dose estimates determined using existing skeletal models. Methods presented in this work were developed in response to the need for dosimetry models which account for these biological and patient-specific factors. Dosimetry models are presented for trabecular bone alpha particle dosimetry as well as a model for cortical bone dosimetry. These radiation transport models are the 3D chord-based infinite spongiosa transport model (3D-CBIST) and the chord-based infinite cortical transport model (CBICT), respectively. Absorbed fraction data for several skeletal tissues for several subjects are presented. Each modeling strategy accounts for biological parameters, such as bone marrow cellularity, not previously incorporated into alpha-particle skeletal dosimetry models used in radiation protection. Using these data a study investigating the variability in alpha-particle absorbed fractions in the human skeleton is also presented. Data is also offered relating skeletal tissue masses in individual bone sites for a range of ages. These data are necessary for dose calculations and have previously only been available as whole body tissue masses. A revised 3D-CBIST model is also presented which allows for changes in endosteum thickness to account for revised target cell location of tissues involved in the radiological

Traumatic skeletal changes

International Nuclear Information System (INIS)

Troeger, J.; Schofer, O.

1985-01-01

Skeleton scintiscanning is indicated in the following cases: (1) Suspected bone injury after clinical examination, the radiograph of the skeletal region in question contributing findings that either do not confirm suspision, or make not clear whether the changes observed are traumatic. (2) Polytrauma. (3) When the accident scenario reported by the persons taking care of the child does not sufficiently explain the skeletal changes observed, or when these persons expressly deny the possibility of a trauma being the cause of findings observed. (4) Suspected or proven battered-child syndrome. (orig./MG) [de

Positron-labeled antioxidant 6-deoxy-6-[{sup 18}F]fluoro-L-ascorbic acid: Increased uptake in transient global ischemic rat brain

Energy Technology Data Exchange (ETDEWEB)

Yamamoto, Fumihiko; Shibata, Shigenobu; Watanabe, Shigenori; Masuda, Kouji; Maeda, Minoru

1996-05-01

The in vivo uptake and distribution of 6-deoxy-6-[{sup 18}F]fluoro-L-ascorbic acid ({sup 18}F-DFA) were investigated in rat brains following postischemic reperfusion. Global cerebral ischemia was induced in male Wistar rats for 20 min by occlusion of four major arteries. Two time points were chosen for {sup 18}F-DFA injection to rats subjected to cerebral ischemia, at the start of recirculation and 5 days following recirculation. The rats were then killed at 2 h after tail-vein administration of {sup 18}F-DFA and tissue radioactivity concentration was determined. Increased uptake of radioactivity in particular brain regions, including the cerebral cortex, hypothalamus, and amygdala following injection of {sup 18}F-DFA, compared to the sham-operated control, was observed 5 days after reperfusion. Similar results were also obtained in in vitro experiments using brain slices. Abnormal in vivo accumulation of {sup 45}Ca, a marker of regional postischemic injury, was observed in these brain regions in tissue dissection experiments. Furthermore, metabolite analysis of nonradioactive DFA using {sup 19}F-NMR showed that DFA remained intact in the postischemic reperfusion brain. The present results indicate that {sup 18}F-DFA increasingly accumulates in damaged regions of postischemic reperfusion brain.

Skeletal sarcoidosis; Skelettsarkoidose

Energy Technology Data Exchange (ETDEWEB)

Freyschmidt, J. [Klinikum Bremen-Mitte, Beratungsstelle und Referenzzentrum fuer Osteoradiologie, Bremen (Germany); Freyschmidt, P. [Dermatologische Gemeinschaftspraxis, Schwalmstadt (Germany)

2016-10-15

Presentation of the etiology, pathology, clinical course, radiology and differential diagnostics of skeletal sarcoidosis. Noncaseating epithelioid cell granulomas can trigger solitary, multiple or disseminated osteolysis, reactive osteosclerosis and/or granulomatous synovitis. The incidence of sarcoidosis is 10-12 per 100,000 inhabitants per year. Skeletal involvement is approximately 14 %. Skeletal involvement occurs almost exclusively in the stage of lymph node and pulmonary manifestation. Most cases of skeletal involvement are clinically asymptomatic. In the case of synovial involvement, unspecific joint complaints (arthralgia) or less commonly arthritis can occur. Typical skin alterations can be diagnostically significant. Punch out lesions osteolysis, coarse destruction and osteosclerosis can occur, which are best visualized with projection radiography and/or computed tomography. Pure bone marrow foci without interaction with the bone can only be detected with magnetic resonance imaging (MRI) and more recently with positron emission tomography (PET), mostly as incidental findings. There is a predeliction for the hand and trunk skeleton. Skeletal tuberculosis, metastases, multiple myeloma, Langerhans cell histiocytosis and sarcoid-like reactions in solid tumors must be differentiated. The key factors for correct diagnosis are thorax radiography, thorax CT and dermatological manifestations. (orig.) [German] Darstellung von Aetiologie, Pathologie, Klinik, Radiologie und Differenzialdiagnose der Skelettsarkoidose. Nichtverkaesende Epitheloidzellgranulome koennen solitaere, multiple oder disseminierte Osteolysen, reaktive Osteosklerosen und/oder eine granulomatoese Synovialitis ausloesen. Inzidenz der Sarkoidose: 10-12/100.000 Einwohner/Jahr. Skelettbeteiligung ca. 14 %. Skelettbeteiligungen kommen fast ausschliesslich im Stadium einer Lymphknoten- und pulmonalen Manifestation vor. Die meisten Skelettbeteiligungen verlaufen klinisch stumm. Bei synovialer

Role of mesoscale eddies in the global ocean uptake of anthropogenic CO{sub 2}; Role des tourbillons de meso-echelle oceaniques dans la distribution et les flux air-mer de CO{sub 2} anthropique a l'echelle globale

Energy Technology Data Exchange (ETDEWEB)

Zouhair, Lachkar

2007-02-15

Mesoscale eddies play a fundamental role in ocean dynamics particularly in the Southern Ocean. Global-scale tracer simulations are typically made at coarse resolution without explicitly modeling eddies. Here we ask what role do eddies play in ocean uptake, storage, and meridional transport of anthropogenic CO{sub 2}, CFC-11 and bomb {delta}{sup 14}C. We made global anthropogenic transient tracer simulations in coarse-resolution, ORCA2, and eddy-permitting, ORCA05 and ORCA025, versions of the ocean modelling system NEMO. We focus on the Southern Ocean where tracer air-sea fluxes are largest. Eddies have little effect on bomb {delta}{sup 14}C uptake and storage. Yet for CFC-11 and anthropogenic CO{sub 2}, increased eddy activity reduces southern extra-tropical uptake by 28% and 25% respectively, thereby providing better agreement with observations. It is shown that the discrepancies in the equilibration times between the three tracers determine their respective sensitivities to the model horizontal resolution. Applying Gent and McWilliams (1990) (GM) parameterization of eddies in the non-eddying version of the model does improve results, but not enough. An in-depth investigation of the mechanisms by which eddies affect the uptake of the transient tracers shows that including mesoscale eddies leads to an overall reduction in the Antarctic Intermediate Water (AAIW) ventilation, and modifies substantially the spatial distribution of their source regions. This investigation reveals also that the GM parameterization still overestimates the ventilation and the subduction of AAIW in the Indian Ocean where the simulated mixed layer is particularly deep during the winter. This work suggests that most current coarse-resolution models may overestimate the ventilation of AAIW in the Indian sector of the Southern Ocean. This study shows also that the use of the GM parameterization may be of limited utility where mixed layer is relatively deep and confirms the general need for a

Pelvic radiograph in skeletal dysplasias: An approach

Directory of Open Access Journals (Sweden)

Manisha Jana

2017-01-01

Full Text Available The bony pelvis is constituted by the ilium, ischium, pubis, and sacrum. The pelvic radiograph is an important component of the skeletal survey performed in suspected skeletal dysplasia. Most of the common skeletal dysplasias have either minor or major radiological abnormalities; hence, knowledge of the normal radiological appearance of bony pelvis is vital for recognizing the early signs of various skeletal dysplasias. This article discusses many common and some uncommon radiological findings on pelvic radiographs along with the specific dysplasia in which they are seen; common differential diagnostic considerations are also discussed.

The role of adipose tissue and excess of fatty acids in the induction of insulin resistance in skeletal muscle

Directory of Open Access Journals (Sweden)

Agnieszka Błachnio-Zabielska

2016-11-01

Full Text Available Skeletal muscle is the main tissue responsible for insulin-stimulated glucose uptake. Consumption of a high-fat diet rich in saturated fats (HFD and obesity are associated with accumulation of intramuscular lipids that leads to several disorders, e.g. insulin resistance (IRes and type 2 diabetes (T2D. The mechanism underlying the induction of IRes is still unknown. It was speculated that accumulation of intramuscular triacylglycerols (TAG is linked to induction of IRes. Now, research focuses on bioactive lipids: long-chain acyl-CoA (LCACoA, diacylglycerols (DAG and ceramides (Cer. It has been demonstrated that accumulation of each of the above-mentioned lipid classes negatively affects the insulin signaling pathway. It is not clear which of those lipids play the most important role in HFD-induced skeletal muscle IRes. The aim of the present work is to present the current knowledge of the role of adipose tissue and excess of fatty acids in the induction of insulin resistance.

Spinal meningeal uptake of technetium-99m methylene diphosphonate in meningeal seeding by malignant lymphoma

International Nuclear Information System (INIS)

Siegal, T.; Or, R.; Matzner, Y.; Samuels, L.D.

1980-01-01

Definite diagnosis of meningeal seeding by systemic cancer relies on the presence of malignant cells in the cerebrospinal fluid (CSF). In the absence of such cells in the CSF, only two other tests strongly suggest the diagnosis - a CT scan and a myelogram. This paper reports a case in which the diagnosis was strongly suggested by an unusual uptake of Tc-99m methylene diphosphonate by the leptomeninges during a skeletal scan and later established by the presence of malignant cells in the CSF. The radionuclide scan may be an additional diagnostic test in some cases with meningeal seeding by systemic cancer

Retrospective review to determine the utility of follow-up skeletal surveys in child abuse evaluations when the initial skeletal survey is normal

Directory of Open Access Journals (Sweden)

Kachelmeyer Andrea

2011-09-01

Full Text Available Abstract Objective The AAP recommends that a follow-up skeletal survey be obtained for all children Methods A retrospective review of radiology records from September 1, 1998 - January 31, 2007 was conducted. Suspected victims of child abuse who were Results Forty-seven children had a negative initial skeletal survey and were included for analysis. The mean age was 6.9 months (SD 5.7; the mean number of days between skeletal surveys was 18.7 (SD 10.1 Four children (8.5% had signs of healing bone trauma on a follow-up skeletal survey. Three of these children (75% had healing rib fractures and one child had a healing proximal humerus fracture. The findings on the follow-up skeletal survey yielded forensically important information in all 4 cases and strengthened the diagnosis of non-accidental trauma. Conclusion 8.5 percent of children with negative initial skeletal surveys had forensically important findings on follow-up skeletal survey that increased the certainty of the diagnosis of non-accidental trauma. A follow-up skeletal survey can be useful even when the initial skeletal survey is negative.

Does Elevated CO2 Alter Silica Uptake in Trees?

Directory of Open Access Journals (Sweden)

Robinson W. Fulweiler

2015-01-01

Full Text Available Human activities have greatly altered global carbon (C and N (N cycling. In fact, atmospheric concentrations of carbon dioxide (CO2 have increased 40% over the last century and the amount of N cycling in the biosphere has more than doubled. In an effort to understand how plants will respond to continued global carbon dioxide fertilization, long-term free-air CO2 enrichment (FACE experiments have been conducted at sites around the globe. Here we examine how atmospheric CO2 enrichment and N fertilization affects the uptake of silicon (Si in the Duke Forest, North Carolina, a stand dominated by Pinus taeda (loblolly pine, and five hardwood species. Specifically, we measured foliar biogenic silica (BSi concentrations in five deciduous and one coniferous species across three treatments: CO2 enrichment, N enrichment, and N and CO2 enrichment. We found no consistent trends in foliar Si concentration under elevated CO2, N fertilization, or combined elevated CO2 and N fertilization. However, two-thirds of the tree species studied here have Si foliar concentrations greater than well-known Si accumulators, such as grasses. Based on net primary production values and aboveground Si concentrations in these trees, we calculated forest Si uptake rates under control and elevated CO2 concentrations. Due largely to increased primary production, elevated CO2 enhanced the magnitude of Si uptake between 20% and 26%, likely intensifying the terrestrial silica pump. This uptake of Si by forests has important implications for Si export from terrestrial systems, with the potential to impact C sequestration and higher trophic levels in downstream ecosystems.

Expression profiling of skeletal muscle following acute and chronic β2-adrenergic stimulation: implications for hypertrophy, metabolism and circadian rhythm

Directory of Open Access Journals (Sweden)

Lynch Gordon S

2009-09-01

administration also appeared to influence some genes associated with the peripheral regulation of circadian rhythm (including nuclear factor interleukin 3 regulated, D site albumin promoter binding protein, and cryptochrome 2. Conclusion This is the first study to utilize gene expression profiling to examine global gene expression in response to acute β2-AR agonist treatment of skeletal muscle. In summary, systemic administration of a β2-AR agonist had a profound effect on global gene expression in skeletal muscle. In terms of hypertrophy, β2-AR agonist treatment altered the expression of several genes associated with myostatin signaling, a previously unreported effect of β-AR signaling in skeletal muscle. This study also demonstrates a β2-AR agonist regulation of circadian rhythm genes, indicating crosstalk between β-AR signaling and circadian cycling in skeletal muscle. Gene expression alterations discovered in this study provides insight into many of the underlying changes in gene expression that mediate β-AR induced skeletal muscle hypertrophy and altered metabolism.

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.)

Substantial global carbon uptake by cement carbonation

OpenAIRE

Xi, Fengming; Davis, Steven J.; Ciais, Philippe; Crawford-Brown, Douglas; Guan, Dabo; Pade, Claus; Shi, Tiemao; Syddall, Mark; Lv, Jie; Ji, Lanzhu; Bing, Longfei; Wang, Jiaoyue; Wei, Wei; Yang, Keun-Hyeok; Lagerblad, Björn

2016-01-01

Calcination of carbonate rocks during the manufacture of cement produced 5% of global CO2 emissions from all industrial process and fossil-fuel combustion in 20131, 2. Considerable attention has been paid to quantifying these industrial process emissions from cement production2, 3, but the natural reversal of the process—carbonation—has received little attention in carbon cycle studies. Here, we use new and existing data on cement materials during cement service life, demolition, and secondar...

Comparison of second molar eruption patterns in patients with skeletal Class II and skeletal Class I malocclusions.

Science.gov (United States)

Brin, Ilana; Camasuvi, Semin; Dali, Nasser; Aizenbud, Dror

2006-12-01

The eruptive positions of the second molars in Class I and Class II malocclusions were studied. Pretreatment records of 221 patients with a mean age of 11.3 years were evaluated. About 19% of them had skeletal Class I, 31% had skeletal maxillary Class II, and 50% had skeletal mandibular Class II malocclusions. The mean values of the dental and chronologic ages of the subjects were similar. The eruptive positions in relation to a reference line, the developmental stages of the patients' second molars and dental ages were recorded from the panoramic roentgenograms. The distribution of the various developmental stages in each malocclusion group was similar, and no association between skeletal malocclusion and dental developmental stage of the second molars was encountered. The eruptive position of the maxillary second molars was more occlusal only in the oldest maxillary Class II group, above 12 years of age (P = .02). These results support, in part, previous reports suggesting that the maxillary second molars may erupt earlier in patients with skeletal maxillary Class II malocclusions.

Skeletal muscle contraction-induced vasodilation in the microcirculation.

Science.gov (United States)

Hong, Kwang-Seok; Kim, Kijeong

2017-10-01

Maximal whole body exercise leads skeletal muscle blood flow to markedly increase to match metabolic demands, a phenomenon termed exercise hyperaemia that is accomplished by increasing vasodilation. However, local vasodilatory mechanisms in response to skeletal muscle contraction remain uncertain. This review highlights metabolic vasodilators released from contracting skeletal muscle, endothelium, or blood cells. As a considerable skeletal muscle vasodilation potentially results in hypotension, sympathetic nerve activity needs to be augmented to elevate cardiac output and blood pressure during dynamic exercise. However, since the enhanced sympathetic vasoconstriction restrains skeletal muscle blood flow, intramuscular arteries have an indispensable ability to blunt sympathetic activity for exercise hyperaemia. In addition, we discuss that mechanical compression of the intramuscular vasculature contributes to causing the initial phase of increasing vasodilation following a single muscle contraction. We have also chosen to focus on conducted (or ascending) electrical signals that evoke vasodilation of proximal feed arteries to elevate blood flow in the microcirculation of skeletal muscle. Endothelial hyperpolarization originating within distal arterioles ascends into the proximal feed arteries, thereby increasing total blood flow in contracting skeletal muscle. This brief review summarizes molecular mechanisms underlying the regulation of skeletal muscle blood flow to a single or sustained muscle contraction.

Myostatin in relation to physical activity and dysglycaemia and its effect on energy metabolism in human skeletal muscle cells.

Science.gov (United States)

Hjorth, M; Pourteymour, S; Görgens, S W; Langleite, T M; Lee, S; Holen, T; Gulseth, H L; Birkeland, K I; Jensen, J; Drevon, C A; Norheim, F

2016-05-01

Some health benefits of exercise may be explained by an altered secretion of myokines. Because previous focus has been on upregulated myokines, we screened for downregulated myokines and identified myostatin. We studied the expression of myostatin in relation to exercise and dysglycaemia in skeletal muscle, adipose tissue and plasma. We further examined some effects of myostatin on energy metabolism in primary human muscle cells and Simpson-Golabi-Behmel syndrome (SGBS) adipocytes. Sedentary men with or without dysglycaemia underwent a 45-min acute bicycle test before and after 12 weeks of combined endurance and strength training. Blood samples and biopsies from m. vastus lateralis and adipose tissue were collected. Myostatin mRNA expression was reduced in skeletal muscle after acute as well as long-term exercise and was even further downregulated by acute exercise on top of 12-week training. Furthermore, the expression of myostatin at baseline correlated negatively with insulin sensitivity. Myostatin expression in the adipose tissue increased after 12 weeks of training and correlated positively with insulin sensitivity markers. In cultured muscle cells but not in SGBS cells, myostatin promoted an insulin-independent increase in glucose uptake. Furthermore, muscle cells incubated with myostatin had an enhanced rate of glucose oxidation and lactate production. Myostatin was differentially expressed in the muscle and adipose tissue in relation to physical activity and dysglycaemia. Recombinant myostatin increased the consumption of glucose in human skeletal muscle cells, suggesting a complex regulatory role of myostatin in skeletal muscle homeostasis. © 2015 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

The skeletal endocannabinoid system: clinical and experimental insights.

Science.gov (United States)

Raphael, Bitya; Gabet, Yankel

2016-05-01

Recently, there has been a rapidly growing interest in the role of cannabinoids in the regulation of skeletal remodeling and bone mass, addressed in basic, translational and clinical research. Since the first publications in 2005, there are more than 1000 publications addressing the skeletal endocannabinoid system. This review focuses on the roles of the endocannabinoid system in skeletal biology via the cannabinoid receptors CB1, CB2 and others. Endocannabinoids play important roles in bone formation, bone resorption and skeletal growth, and are sometimes age, gender, species and strain dependent. Controversies in the literature and potential therapeutic approaches targeting the endocannabinoid system in skeletal disorders are also discussed.

GLP-1 increases microvascular recruitment but not glucose uptake in human and rat skeletal muscle

DEFF Research Database (Denmark)

Sjøberg, Kim Anker; Holst, Jens Juul; Rattigan, Stephen

2014-01-01

The insulinotropic gut hormone, glucagon-like-peptide-1 (GLP-1) has been proposed to have effects on vascular function and glucose disposal. However, whether GLP-1 is able to increase microvascular recruitment (MVR) in humans has not been investigated. GLP-1 was infused in the femoral artery...... in overnight fasted healthy young men. Microvascular recruitment was measured with real time contrast-enhanced ultrasound and leg glucose uptake by the leg balance technique with and without inhibition of the insulinotropic response of GLP-1 by co-infusion of octreotide. As a positive control, MVR and leg...

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...

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....

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...

A Mathematical Model of Oxygen Transport in Skeletal Muscle During Hindlimb Unloading

Science.gov (United States)

Causey, Laura; Lewandowski, Beth E.; Weinbaum, Sheldon

2014-01-01

During hindlimb unloading (HU) dramatic fluid shifts occur within minutes of the suspension, leading to a less precise matching of blood flow to O2 demands of skeletal muscle. Vascular resistance directs blood away from certain muscles, such as the soleus (SOL). The muscle volume gradually reduces in these muscles so that eventually the relative blood flow returns to normal. It is generally believed that muscle volume change is not due to O2 depletion, but a consequence of disuse. However, the volume of the unloaded rat muscle declines over the course of weeks, whereas the redistribution of blood flow occurs immediately. Using a Krogh Cylinder Model, the distribution of O2 was predicted in two skeletal muscles: SOL and gastrocnemius (GAS). Effects of the muscle blood flow, volume, capillary density, and O2 uptake, are included to calculate the pO2 at rest and after 10 min and 15 days of unloading. The model predicts that 32 percent of the SOL muscle tissue has a pO2 1.25 mm Hg within 10 min, whereas the GAS maintains normal O2 levels, and that equilibrium is reached only as the SOL muscle cells degenerate. The results provide evidence that there is an inadequate O2 supply to the mitochondria in the SOL muscle after 10 min HU.

Skeletal shape correspondence via entropy minimization

Science.gov (United States)

Tu, Liyun; Styner, Martin; Vicory, Jared; Paniagua, Beatriz; Prieto, Juan Carlos; Yang, Dan; Pizer, Stephen M.

2015-03-01

Purpose: Improving the shape statistics of medical image objects by generating correspondence of interior skeletal points. Data: Synthetic objects and real world lateral ventricles segmented from MR images. Method(s): Each object's interior is modeled by a skeletal representation called the s-rep, which is a quadrilaterally sampled, folded 2-sided skeletal sheet with spoke vectors proceeding from the sheet to the boundary. The skeleton is divided into three parts: up-side, down-side and fold-curve. The spokes on each part are treated separately and, using spoke interpolation, are shifted along their skeletal parts in each training sample so as to tighten the probability distribution on those spokes' geometric properties while sampling the object interior regularly. As with the surface-based correspondence method of Cates et al., entropy is used to measure both the probability distribution tightness and sampling regularity. The spokes' geometric properties are skeletal position, spoke length and spoke direction. The properties used to measure the regularity are the volumetric subregions bounded by the spokes, their quadrilateral sub-area and edge lengths on the skeletal surface and on the boundary. Results: Evaluation on synthetic and real world lateral ventricles demonstrated improvement in the performance of statistics using the resulting probability distributions, as compared to methods based on boundary models. The evaluation measures used were generalization, specificity, and compactness. Conclusions: S-rep models with the proposed improved correspondence provide significantly enhanced statistics as compared to standard boundary models.

[Molecular mechanisms of skeletal muscle hypertrophy].

Science.gov (United States)

Astratenkova, I V; Rogozkin, V A

2014-06-01

Enzymes Akt, AMPK, mTOR, S6K and PGC-1a coactivator take part in skeletal muscles in the regulation of synthesis of proteins. The expression of these proteins is regulated by growth factors, hormones, nutrients, mechanical loading and leads to an increase in muscle mass and skeletal muscle hypertrophy. The review presents the results of studies published in the past four years, which expand knowledge on the effects of various factors on protein synthesis in skeletal muscle. The attention is focused on the achievements that reveal and clarify the signaling pathways involved in the regulation of protein synthesis in skeletal muscle. The central place is taken by mTOR enzyme which controls and regulates the main stages of the cascade of reactions of muscle proteins providing synthesis in the conditions of human life. coactivator PGC-1a.

(-)-Epicatechin administration and exercising skeletal muscle vascular control and microvascular oxygenation in healthy rats.

Science.gov (United States)

Copp, Steven W; Inagaki, Tadakatsu; White, Michael J; Hirai, Daniel M; Ferguson, Scott K; Holdsworth, Clark T; Sims, Gabrielle E; Poole, David C; Musch, Timothy I

2013-01-15

Consumption of the dietary flavanol (-)-epicatechin (EPI) is associated with enhanced endothelial function and augmented skeletal muscle capillarity and mitochondrial volume density. The potential for EPI to improve peripheral vascular function and muscle oxygenation during exercise is unknown. We tested the hypothesis that EPI administration in healthy rats would improve treadmill exercise performance secondary to elevated skeletal muscle blood flow and vascular conductance [VC, blood flow/mean arterial pressure (MAP)] and improved skeletal muscle microvascular oxygenation. Rats received water (control, n = 12) or 4 mg/kg EPI (n = 12) via oral gavage daily for 24 days. Exercise endurance capacity and peak O(2) uptake (Vo(2) peak) were measured via treadmill runs to exhaustion. MAP (arterial catheter) and blood flow (radiolabeled microspheres) were measured and VC was calculated during submaximal treadmill exercise (25 m/min, 5% grade). Spinotrapezius muscle microvascular O(2) pressure (Po(2mv)) was measured (phosphorescence quenching) during electrically induced twitch (1 Hz) contractions. In conscious rats, EPI administration resulted in lower (↓~5%) resting (P = 0.03) and exercising (P = 0.04) MAP. There were no differences in exercise endurance capacity, Vo(2) peak, total exercising hindlimb blood flow (control, 154 ± 13; and EPI, 159 ± 8 ml·min(-1)·100 g(-1), P = 0.68), or VC (control, 1.13 ± 0.10; and EPI, 1.24 ± 0.08 ml·min(-1)·100 g(-1)·mmHg(-1), P = 0.21) between groups. Following anesthesia, EPI resulted in lower MAP (↓~16%) but did not impact resting Po(2mv) or any kinetics parameters (P > 0.05 for all) during muscle contractions compared with control. EPI administration (4 mg·kg(-1)·day(-1)) improved modestly cardiovascular function (i.e., ↓MAP) with no impact on exercise performance, total exercising skeletal muscle blood flow and VC, or contracting muscle microvascular oxygenation in healthy rats.

Arsenic uptake and phytoremediation potential by arbuscular mycorrhizal fungi

Science.gov (United States)

Xinhua He; Erik Lilleskov

2014-01-01

Arsenic (As) contamination of soils and water is a global problem because of its impacts on ecosystems and human health. Various approaches have been attempted for As remediation, with limited success. Arbuscular mycorrhizal (AM) fungi play vital roles in the uptake of water and essential nutrients, especially phosphorus (P), and hence enhance plant performance and...

Large uncertainty in carbon uptake potential of land-based climate-change mitigation efforts.

Science.gov (United States)

Krause, Andreas; Pugh, Thomas A M; Bayer, Anita D; Li, Wei; Leung, Felix; Bondeau, Alberte; Doelman, Jonathan C; Humpenöder, Florian; Anthoni, Peter; Bodirsky, Benjamin L; Ciais, Philippe; Müller, Christoph; Murray-Tortarolo, Guillermo; Olin, Stefan; Popp, Alexander; Sitch, Stephen; Stehfest, Elke; Arneth, Almut

2018-07-01

Most climate mitigation scenarios involve negative emissions, especially those that aim to limit global temperature increase to 2°C or less. However, the carbon uptake potential in land-based climate change mitigation efforts is highly uncertain. Here, we address this uncertainty by using two land-based mitigation scenarios from two land-use models (IMAGE and MAgPIE) as input to four dynamic global vegetation models (DGVMs; LPJ-GUESS, ORCHIDEE, JULES, LPJmL). Each of the four combinations of land-use models and mitigation scenarios aimed for a cumulative carbon uptake of ~130 GtC by the end of the century, achieved either via the cultivation of bioenergy crops combined with carbon capture and storage (BECCS) or avoided deforestation and afforestation (ADAFF). Results suggest large uncertainty in simulated future land demand and carbon uptake rates, depending on the assumptions related to land use and land management in the models. Total cumulative carbon uptake in the DGVMs is highly variable across mitigation scenarios, ranging between 19 and 130 GtC by year 2099. Only one out of the 16 combinations of mitigation scenarios and DGVMs achieves an equivalent or higher carbon uptake than achieved in the land-use models. The large differences in carbon uptake between the DGVMs and their discrepancy against the carbon uptake in IMAGE and MAgPIE are mainly due to different model assumptions regarding bioenergy crop yields and due to the simulation of soil carbon response to land-use change. Differences between land-use models and DGVMs regarding forest biomass and the rate of forest regrowth also have an impact, albeit smaller, on the results. Given the low confidence in simulated carbon uptake for a given land-based mitigation scenario, and that negative emissions simulated by the DGVMs are typically lower than assumed in scenarios consistent with the 2°C target, relying on negative emissions to mitigate climate change is a highly uncertain strategy. © 2018 John

Archform comparisons between skeletal class II and III malocclusions.

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Wei Zou

Full Text Available The purpose of this cross-sectional research was to explore the relationship of the mandibular dental and basal bone archforms between severe Skeletal Class II (SC2 and Skeletal Class III (SC3 malocclusions. We also compared intercanine and intermolar widths in these two malocclusion types. Thirty-three virtual pretreatment mandibular models (Skeletal Class III group and Thirty-five Skeletal Class II group pretreatment models were created with a laser scanning system. FA (the midpoint of the facial axis of the clinical crownand WALA points (the most prominent point on the soft-tissue ridgewere employed to produce dental and basal bone archforms, respectively. Gained scatter diagrams of the samples were processed by nonlinear regression analysis via SPSS 17.0. The mandibular dental and basal bone intercanine and intermolar widths were significantly greater in the Skeletal Class III group compared to the Skeletal Class II group. In both groups, a moderate correlation existed between dental and basal bone arch widths in the canine region, and a high correlation existed between dental and basal bone arch widths in the molar region. The coefficient of correlation of the Skeletal Class III group was greater than the Skeletal Class II group. Fourth degree, even order power functions were used as best-fit functions to fit the scatter plots. The radius of curvature was larger in Skeletal Class III malocclusions compared to Skeletal Class II malocclusions (rWALA3>rWALA2>rFA3>rFA2. In conclusion, mandibular dental and basal intercanine and intermolar widths were significantly different between the two groups. Compared with Skeletal Class II subjects, the mandibular archform was more flat for Skeletal Class III subjects.

Ameliorative effects of polyunsaturated fatty acids against palmitic acid-induced insulin resistance in L6 skeletal muscle cells

Directory of Open Access Journals (Sweden)

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.

Generalized skeletal pathology: Results of radionuclide studies

International Nuclear Information System (INIS)

Fueger, G.F.; Aigner, R.

1987-01-01

Generalized pathological changes may involve the skeleton systematically (bone tissue, bone marrow) or at multiple sites involving destruction or infiltration. Appropriate radionuclide studies include total-body bone or bone marrow scintigraphy, absorptiometry (osteodensitometry) and the 24 h whole-body retention measurement. Established radioindicators are 99m-Tc-(hydroxy)methylendiphosphonate (HMDP or MDP) and 99m-Tc-human serumalbumin-nanocolloid. Absorptiometry of the forearm, extended by computer-assisted transaxial tomography, may be expected to prove as the most efficient method of bone density measurement. The 24 h whole-body retention measurement is useful for the diagnosis and follow-up of metabolic and endocrine osteopathies, if the very same osteotropic 99m-Tc-chelate is used. Whole-body bone scintigraphy today is one of the most important radionuclide studies for diagnosis and follow-up of skeletal metastases. Scintigraphy provides evidence of skeletal metastases several months earlier than radiological examinations. In about 40 percent of patients with cancer of the prostate, scintigraphy provided positive findings of skeletal metastases in the absence of both pain and increased levels of phosphatase. In patients with a history of malignancy, 60 percent of solitary findings on skeletal scintigraphy are metastases. The frequency of false negative findings obtained by whole-body skeletal scintigraphy are metastases. The frequency of false negative findings obtained by whole-body skeletal scintigraphy ranges from 2 to 4%. Compared to skeletal scintigraphy, bone marrow scintigraphy frequently yields significant additional findings in cases of plasmocytoma, histiocytoma, lymphoma and haemoblastoses. (orig.) [de

Thyroid Hormone Signaling in Male Mouse Skeletal Muscle Is Largely Independent of D2 in Myocytes

Science.gov (United States)

Werneck-de-Castro, Joao P.; Fonseca, Tatiana L.; Ignacio, Daniele L.; Fernandes, Gustavo W.; Andrade-Feraud, Cristina M.; Lartey, Lattoya J.; Ribeiro, Marcelo B.; Ribeiro, Miriam O.; Gereben, Balazs

2015-01-01

The type 2 deiodinase (D2) activates the prohormone T4 to T3. D2 is expressed in skeletal muscle (SKM), and its global inactivation (GLOB-D2KO mice) reportedly leads to skeletal muscle hypothyroidism and impaired differentiation. Here floxed Dio2 mice were crossed with mice expressing Cre-recombinase under the myosin light chain 1f (cre-MLC) to disrupt D2 expression in the late developmental stages of skeletal myocytes (SKM-D2KO). This led to a loss of approximately 50% in D2 activity in neonatal and adult SKM-D2KO skeletal muscle and about 75% in isolated SKM-D2KO myocytes. To test the impact of Dio2 disruption, we measured soleus T3 content and found it to be normal. We also looked at the expression of T3-responsive genes in skeletal muscle, ie, myosin heavy chain I, α-actin, myosin light chain, tropomyosin, and serca 1 and 2, which was preserved in neonatal SKM-D2KO hindlimb muscles, at a time that coincides with a peak of D2 activity in control animals. In adult soleus the baseline level of D2 activity was about 6-fold lower, and in the SKM-D2KO soleus, the expression of only one of five T3-responsive genes was reduced. Despite this, adult SKM-D2KO animals performed indistinguishably from controls on a treadmill test, running for approximately 16 minutes and reached a speed of about 23 m/min; muscle strength was about 0.3 mN/m·g body weight in SKM-D2KO and control ankle muscles. In conclusion, there are multiple sources of D2 in the mouse SKM, and its role is limited in postnatal skeletal muscle fibers. PMID:26214036

Skeletal Stem Cells: Origins, Functions and Uncertainties.

Science.gov (United States)

Mohamed, Fatma F; Franceschi, Renny T

2017-12-01

The development and maintenance of the skeleton requires a steady source of skeletal progenitors to provide the osteoblasts and chondrocytes necessary for bone and cartilage growth and development. The current model for skeletal stem cells (SSCs) posits that SSC/progenitor cells are present in bone marrow (BM) and other osteogenic sites such as cranial sutures where they undergo self-renewal and differentiation to give rise to the main skeletal tissues. SSCs hold great promise for understanding skeletal biology and genetic diseases of bone as well as for the advancement of bone tissue engineering and regenerative medicine strategies. In the past few years, a considerable effort has been devoted to identifying and purifying skeletal stem cells and determining their contribution to bone formation and homeostasis. Here, we review recent progress in this area with particular emphasis on the discovery of specific SSC markers, their use in tracking the progression of cell populations along specific lineages and the regulation of SSCs in both the appendicular and cranial skeleton.

Skeletal MR imaging: Correlation with skeletal scintigraphy

International Nuclear Information System (INIS)

Colletti, P.M.; Raval, J.K.; Ford, P.V.; Benson, R.C.; Kerr, R.M.; Boswell, W.D.; Siegel, M.E.; Ralls, P.W.

1987-01-01

Skeletal MR images bone marrow while skeletal scintigraphy uses bone metabolism to demonstrate abnormalities. The purpose of this paper is to correlate these MR and scintigraphic findings. T1 and T2 MR images at 0.5 T were correlated with planar bone scintigraphy (RN) using Tc-99m MDP in 56 patients. Of 23 cases with suspected spinal metastases, 19 were positive by MR imaging, 16 by RN. Individual lesions were shown better by MR imaging in five and by RN in two. These two cases had scoliosis, a potential difficulty with MR imaging. In 14 cases of suspected avascular necrosis (AVN), MR imaging was positive in 13 while RN was positive in ten. One negative case by RN had bilateral AVN by MR imaging. Four skull lesions shown easily by RN were seen only in retrospect on MR images. MR imaging is advantageous in evaluating bones with predominant marrow such as vertebrae or the femoral head, while RN is superior in areas primarily composed of cortical bone such as the skull

Insulin acutely improves mitochondrial function of rat and human skeletal muscle by increasing coupling efficiency of oxidative phosphorylation.

Science.gov (United States)

Nisr, Raid B; Affourtit, Charles

2014-02-01

Insulin is essential for the regulation of fuel metabolism and triggers the uptake of glucose by skeletal muscle. The imported glucose is either stored or broken down, as insulin stimulates glycogenesis and ATP synthesis. The mechanism by which ATP production is increased is incompletely understood at present and, generally, relatively little functional information is available on the effect of insulin on mitochondrial function. In this paper we have exploited extracellular flux technology to investigate insulin effects on the bioenergetics of rat (L6) and human skeletal muscle myoblasts and myotubes. We demonstrate that a 20-min insulin exposure significantly increases (i) the cell respiratory control ratio, (ii) the coupling efficiency of oxidative phosphorylation, and (iii) the glucose sensitivity of anaerobic glycolysis. The improvement of mitochondrial function is explained by an insulin-induced immediate decrease of mitochondrial proton leak. Palmitate exposure annuls the beneficial mitochondrial effects of insulin. Our data improve the mechanistic understanding of insulin-stimulated ATP synthesis, and reveal a hitherto undisclosed insulin sensitivity of cellular bioenergetics that suggests a novel way of detecting insulin responsiveness of cells. © 2013.

Insulin acutely improves mitochondrial function of rat and human skeletal muscle by increasing coupling efficiency of oxidative phosphorylation☆

Science.gov (United States)

Nisr, Raid B.; Affourtit, Charles

2014-01-01

Insulin is essential for the regulation of fuel metabolism and triggers the uptake of glucose by skeletal muscle. The imported glucose is either stored or broken down, as insulin stimulates glycogenesis and ATP synthesis. The mechanism by which ATP production is increased is incompletely understood at present and, generally, relatively little functional information is available on the effect of insulin on mitochondrial function. In this paper we have exploited extracellular flux technology to investigate insulin effects on the bioenergetics of rat (L6) and human skeletal muscle myoblasts and myotubes. We demonstrate that a 20-min insulin exposure significantly increases (i) the cell respiratory control ratio, (ii) the coupling efficiency of oxidative phosphorylation, and (iii) the glucose sensitivity of anaerobic glycolysis. The improvement of mitochondrial function is explained by an insulin-induced immediate decrease of mitochondrial proton leak. Palmitate exposure annuls the beneficial mitochondrial effects of insulin. Our data improve the mechanistic understanding of insulin-stimulated ATP synthesis, and reveal a hitherto undisclosed insulin sensitivity of cellular bioenergetics that suggests a novel way of detecting insulin responsiveness of cells. PMID:24212054

Activation of AMPK improves inflammation and insulin resistance in adipose tissue and skeletal muscle from pregnant women.

Science.gov (United States)

Liong, Stella; Lappas, Martha

2015-12-01

Gestational diabetes mellitus (GDM) is characterised by maternal peripheral insulin resistance and inflammation. Sterile inflammation and bacterial infection are key mediators of this enhanced inflammatory response. Adenosine monophosphate (AMP)-activated kinase (AMPK), which is decreased in insulin resistant states, possesses potent pro-inflammatory actions. There are, however, no studies on the role of AMPK in pregnancies complicated by GDM. Thus, the aims of this study were (i) to compare the expression of AMPK in adipose tissue and skeletal muscle from women with GDM and normal glucose-tolerant (NGT) pregnant women; and (ii) to investigate the effect of AMPK activation on inflammation and insulin resistance induced by the bacterial endotoxin lipopolysaccharide (LPS) and the pro-inflammatory cytokine IL-1β. When compared to NGT pregnant women, AMPKα activity was significantly lower in women with GDM as evidenced by a decrease in threonine phosphorylation of AMPKα. Activation of AMPK, using two pharmacologically distinct compounds, AICAR or phenformin, significantly suppressed LPS- or IL-1β-induced gene expression and secretion of pro-inflammatory cytokine IL-6, the chemokines IL-8 and MCP-1, and COX-2 and subsequent prostaglandin release from adipose tissue and skeletal muscle. In addition, activators of AMPK decreased skeletal muscle insulin resistance induced by LPS or IL-1β as evidenced by increased insulin-stimulated phosphorylation of IRS-1, GLUT-4 expression and glucose uptake. These findings suggest that AMPK may play an important role in inflammation and insulin resistance.

Reduced expression of nuclear-encoded genes involved in mitochondrial oxidative metabolism in skeletal muscle of insulin-resistant women with polycystic ovary syndrome

DEFF Research Database (Denmark)

Skov, Vibe; Glintborg, Dorte; Knudsen, Steen

2007-01-01

Insulin resistance in skeletal muscle is a major risk factor for the development of type 2 diabetes in women with polycystic ovary syndrome (PCOS). In patients with type 2 diabetes, insulin resistance in skeletal muscle is associated with abnormalities in insulin signaling, fatty acid metabolism......, and mitochondrial oxidative phosphorylation (OXPHOS). In PCOS patients, the molecular mechanisms of insulin resistance are, however, less well characterized. To identify biological pathways of importance for the pathogenesis of insulin resistance in PCOS, we compared gene expression in skeletal muscle...... of metabolically characterized PCOS patients (n = 16) and healthy control subjects (n = 13) using two different approaches for global pathway analysis: gene set enrichment analysis (GSEA 1.0) and gene map annotator and pathway profiler (GenMAPP 2.0). We demonstrate that impaired insulin-stimulated total, oxidative...

Determinants of relative skeletal maturity in South African children.

Science.gov (United States)

Hawley, Nicola L; Rousham, Emily K; Johnson, William; Norris, Shane A; Pettifor, John M; Cameron, Noël

2012-01-01

The variation of skeletal maturity about chronological age is a sensitive indicator of population health. Age appropriate or advanced skeletal maturity is a reflection of adequate environmental and social conditions, whereas delayed maturation suggests inadequate conditions for optimal development. There remains a paucity of data, however, to indicate which specific biological and environmental factors are associated with advancement or delay in skeletal maturity. The present study utilises longitudinal data from the South African Birth to Twenty (Bt20) study to indentify predictors of relative skeletal maturity (RSM) in early adolescence. A total of 244 black South African children (n=131 male) were included in this analysis. Skeletal maturity at age 9/10 years was assessed using the Tanner and Whitehouse III RUS technique. Longitudinal data on growth, socio-economic position and pubertal development were entered into sex-specific multivariable general linear regression models with relative skeletal maturity (skeletal age-chronological age) as the outcome. At 9/10 years of age males showed an average of 0.66 years delay in skeletal maturation relative to chronological age. Females showed an average of 1.00 year delay relative to chronological age. In males, being taller at 2 years (pdetermining the rate of skeletal maturation during childhood independently of current stature. Copyright © 2011 Elsevier Inc. All rights reserved.

Age-related normal uptake of {sup 99m}Tc-MDP in the lower spine

Energy Technology Data Exchange (ETDEWEB)

Sundkvist, G.M.G. [Dept. of Clinical Physiology, Centralsjukhuset, Kristianstad (Sweden); Lilja, B. [Dept. of Clinical Physiology, Universitetssjukhuset MAS, Malmoe (Sweden); Mattsson, S. [Dept. of Radiation Physics, Universitetssjukhuset MAS, Malmoe (Sweden)

1997-03-01

Aim: The uptake of {sup 99m}Tc-MDP in the lower spine was quantified in connection with ordinary bone scintigraphy. Methods: Fifty-seven women and seventy-two men (aged 20-69 y), with no signs of metabolic or malignant disease and no history of back pain or atraumatic fractures, were included in the study. Results: The women showed an increase in {sup 99m}Tc-MDP uptake from the age of 20 y to about 45 y with a decrease from the time of menopause. In contrast to women, the uptake in men showed a slight decrease from the age of 20 y to about 50 y and thereafter a more marked decrease was seen. The major difference between men and women is the high premenopausal uptake in the female skeleton. Conclusion: An understanding of age-related changes in {sup 99m}Tc-MDP uptake, which are indices of the skeletal metabolism, is of importance especially in prevention and treatment of osteoporosis, a common disorder in postmenopausal women. (orig.) [Deutsch] Ziel: In Verbindung mit einer routinemaessigen Skelettszintigraphie wurde die Speicherung von {sup 99m}Tc-MDP in der unteren Wirbelsaeule quantifiziert. Methoden: 57 Frauen und 22 Maenner (Alter von 20-69 Jahren) ohne metabolische oder boesartige Erkrankungen sowie ohne Rueckenschmerzen oder Wirbelsinterungen wurden in die Studien aufgenommen. Ergebnisse: Bei Frauen zeigte sich ein Anstieg der {sup 99m}Tc-MDP-Speicherung zwischen den Altersabschnitten 20 bis 45 Jahre und dann ein Abfall waehrend der Menopause. Im Gegensatz hierzu zeigte sich bei Maennern ein leichter Abfall der Speicherung vom 20. bis 50. Lebensjahr und danach eine noch staerkere Abnahme. Der Hauptunterschied zwischen den Geschlechtern ist die relativ hohe Speicherung im weiblichen Skelett praemenopausal. Schlussfolgerung: Das Verstaendnis der Altersbeziehungen der {sup 99m}Tc-MDP-Speicherung als Indikator des Knochenstoffwechsels ist fuer Praevention und Behandlung der postmenopausalen Osteoporose wichtig. (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...

The impact of endurance exercise on global and AMPK gene-specific DNA methylation

Energy Technology Data Exchange (ETDEWEB)

King-Himmelreich, Tanya S.; Schramm, Stefanie; Wolters, Miriam C.; Schmetzer, Julia; Möser, Christine V.; Knothe, Claudia [pharmazentrum frankfurt/ZAFES, Institut für Klinische Pharmakologie, Klinikum der Goethe-Universität Frankfurt, Theodor Stern Kai 7, 60590, Frankfurt am Main (Germany); Resch, Eduard [Fraunhofer Institute for Molecular Biology and Applied Ecology (IME), Project Group for Translational Medicine & Pharmacology (TMP), 60596, Frankfurt/Main (Germany); Peil, Johannes [Sports Clinic, Bad Nauheim, MCI GmbH, In der Aue 30-32, 61231, Bad Nauheim (Germany); Geisslinger, Gerd [pharmazentrum frankfurt/ZAFES, Institut für Klinische Pharmakologie, Klinikum der Goethe-Universität Frankfurt, Theodor Stern Kai 7, 60590, Frankfurt am Main (Germany); Fraunhofer Institute for Molecular Biology and Applied Ecology (IME), Project Group for Translational Medicine & Pharmacology (TMP), 60596, Frankfurt/Main (Germany); Niederberger, Ellen, E-mail: e.niederberger@em.uni-frankfurt.de [pharmazentrum frankfurt/ZAFES, Institut für Klinische Pharmakologie, Klinikum der Goethe-Universität Frankfurt, Theodor Stern Kai 7, 60590, Frankfurt am Main (Germany)

2016-05-27

Alterations in gene expression as a consequence of physical exercise are frequently described. The mechanism of these regulations might depend on epigenetic changes in global or gene-specific DNA methylation levels. The AMP-activated protein kinase (AMPK) plays a key role in maintenance of energy homeostasis and is activated by increases in the AMP/ATP ratio as occurring in skeletal muscles after sporting activity. To analyze whether exercise has an impact on the methylation status of the AMPK promoter, we determined the AMPK methylation status in human blood samples from patients before and after sporting activity in the context of rehabilitation as well as in skeletal muscles of trained and untrained mice. Further, we examined long interspersed nuclear element 1 (LINE-1) as indicator of global DNA methylation changes. Our results revealed that light sporting activity in mice and humans does not alter global DNA methylation but has an effect on methylation of specific CpG sites in the AMPKα2 gene. These regulations were associated with a reduced AMPKα2 mRNA and protein expression in muscle tissue, pointing at a contribution of the methylation status to AMPK expression. Taken together, these results suggest that exercise influences AMPKα2 gene methylation in human blood and eminently in the skeletal muscle of mice and therefore might repress AMPKα2 gene expression. -- Highlights: •AMPK gene methylation increases after moderate endurance exercise in humans and mice. •AMPKα mRNA and protein decrease after moderate endurance exercise in mice. •Global DNA methylation is not affected under the same conditions.

The impact of endurance exercise on global and AMPK gene-specific DNA methylation

International Nuclear Information System (INIS)

King-Himmelreich, Tanya S.; Schramm, Stefanie; Wolters, Miriam C.; Schmetzer, Julia; Möser, Christine V.; Knothe, Claudia; Resch, Eduard; Peil, Johannes; Geisslinger, Gerd; Niederberger, Ellen

2016-01-01

Alterations in gene expression as a consequence of physical exercise are frequently described. The mechanism of these regulations might depend on epigenetic changes in global or gene-specific DNA methylation levels. The AMP-activated protein kinase (AMPK) plays a key role in maintenance of energy homeostasis and is activated by increases in the AMP/ATP ratio as occurring in skeletal muscles after sporting activity. To analyze whether exercise has an impact on the methylation status of the AMPK promoter, we determined the AMPK methylation status in human blood samples from patients before and after sporting activity in the context of rehabilitation as well as in skeletal muscles of trained and untrained mice. Further, we examined long interspersed nuclear element 1 (LINE-1) as indicator of global DNA methylation changes. Our results revealed that light sporting activity in mice and humans does not alter global DNA methylation but has an effect on methylation of specific CpG sites in the AMPKα2 gene. These regulations were associated with a reduced AMPKα2 mRNA and protein expression in muscle tissue, pointing at a contribution of the methylation status to AMPK expression. Taken together, these results suggest that exercise influences AMPKα2 gene methylation in human blood and eminently in the skeletal muscle of mice and therefore might repress AMPKα2 gene expression. -- Highlights: •AMPK gene methylation increases after moderate endurance exercise in humans and mice. •AMPKα mRNA and protein decrease after moderate endurance exercise in mice. •Global DNA methylation is not affected under the same conditions.

Comparison of standardized uptake values measured on 18F-NaF PET/CT scans using three different tube current intensities

OpenAIRE

Agnes Araujo Valadares; Paulo Schiavom Duarte; Eduardo Bechtloff Woellner; George Barberio Coura-Filho; Marcelo Tatit Sapienza; Carlos Alberto Buchpiguel

2015-01-01

Objective: To analyze standardized uptake values (SUVs) using three different tube current intensities for attenuation correction on 18FNaF PET/CT scans. Materials and Methods: A total of 254 18F-NaF PET/CT studies were analyzed using 10, 20 and 30 mAs. The SUVs were calculated in volumes of interest (VOIs) drawn on three skeletal regions, namely, right proximal humeral diaphysis (RH), right proximal femoral diaphysis (RF), and first lumbar vertebra (LV1) in a total of 712 VOIs. The analyses ...

Aberrant and alternative splicing in skeletal system disease.

Science.gov (United States)

Fan, Xin; Tang, Liling

2013-10-01

The main function of skeletal system is to support the body and help movement. A variety of factors can lead to skeletal system disease, including age, exercise, and of course genetic makeup and expression. Pre-mRNA splicing plays a crucial role in gene expression, by creating multiple protein variants with different biological functions. The recent studies show that several skeletal system diseases are related to pre-mRNA splicing. This review focuses on the relationship between pre-mRNA splicing and skeletal system disease. On the one hand, splice site mutation that leads to aberrant splicing often causes genetic skeletal system disease, like COL1A1, SEDL and LRP5. On the other hand, alternative splicing without genomic mutation may generate some marker protein isoforms, for example, FN, VEGF and CD44. Therefore, understanding the relationship between pre-mRNA splicing and skeletal system disease will aid in uncovering the mechanism of disease and contribute to the future development of gene therapy. © 2013 Elsevier B.V. All rights reserved.

[Skeletal anchorage in the past, today and tomorrow].

Science.gov (United States)

Melsen, Birte; Dalstra, Michel

2017-03-01

Skeletal anchorage was not introduced as an alternative to conventional anchorage modalities. The first skeletal anchorage was a ligature through a hole in the infrazygomatic crest. This was replaced by surgical screws and finally the TADs, which were optimized with respect to the material and morphology, were developed. A bracket-like head allows for the use of the mini-implant as indirect anchorage, but should not be a tool for lost control resulting from badly planned biomechanics or failing compliance. Skeletal anchorage should serve as an adjunct to correct biomechanics, to enable treatments that could not be performed prior to the introduction of skeletal anchorage. The aim of this study was to test the hypothesis that temporary anchorage mini-screws help maintain bone density, height and width of alveolar processes in the extraction sites, and thus prevent the thinning of the alveolar ridge usually observed. In adult patients with degenerated dentitions the application of skeletal anchorage can allow for the displacement of teeth where no anchorage units are present, but also for the redevelopment and maintenance of atrophic alveolar bone. The basis for the optimal use of skeletal anchorage is that the correct line of action for the desired tooth displacement is defined and the necessary force system constructed either with the skeletal anchorage as direct or as indirect anchorage. After a period, during which osseointegrated implants were used as anchorage for tooth movement and bone maintenance, it was accepted that the mini-implants could serve also as anchorage for skeletal displacements avoiding loading of teeth. © EDP Sciences, SFODF, 2017.

Knee radiography in the diagnosis of skeletal dysplasias

International Nuclear Information System (INIS)

Kwee, Thomas C.; Beek, Frederik J.A.; Nievelstein, Rutger A.J.; Beemer, Frits A.

2006-01-01

Flattening of the epiphyses of long bones is seen in several skeletal dysplasias and standardized measurements on a radiograph of the knee to detect skeletal dysplasias using this feature have been described. Since then only two other studies in which this method was used have been published, and both included only a small number of children and neither had a control group. In addition, the Dutch National Working Group on Skeletal Dysplasias began to have doubts about the reliability of the method. We therefore decided to re-evaluate its accuracy in a population of children with and without a skeletal dysplasia. To determine the diagnostic value of standardized measurements on conventional AP radiographs of the knee in children with a skeletal dysplasia. Subjects and methods: We measured the distal femoral metaphysis and epiphysis according to the published method on conventional AP radiographs of the knee in 45 healthy children and 52 children with a skeletal dysplasia. We compared graphically the height of the distal femoral epiphysis with its width and with the width of the femoral metaphysis. Receiver operating characteristic (ROC) curves were calculated for each group of children. All graphs showed a considerable overlap between children with a skeletal dysplasia and healthy children. The size of the area under the ROC curves for the different groups was small, varying between 0.567 and 0.653. This method does not discriminate between children with a skeletal dysplasia and healthy children. We therefore consider it to be of little diagnostic value. (orig.)

Mechanical modeling of skeletal muscle functioning

NARCIS (Netherlands)

van der Linden, B.J.J.J.

1998-01-01

For movement of body or body segments is combined effort needed of the central nervous system and the muscular-skeletal system. This thesis deals with the mechanical functioning of skeletal muscle. That muscles come in a large variety of geometries, suggest the existence of a relation between muscle

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.

A unified anatomy ontology of the vertebrate skeletal system.

Directory of Open Access Journals (Sweden)

Wasila M Dahdul

Full Text Available The skeleton is of fundamental importance in research in comparative vertebrate morphology, paleontology, biomechanics, developmental biology, and systematics. Motivated by research questions that require computational access to and comparative reasoning across the diverse skeletal phenotypes of vertebrates, we developed a module of anatomical concepts for the skeletal system, the Vertebrate Skeletal Anatomy Ontology (VSAO, to accommodate and unify the existing skeletal terminologies for the species-specific (mouse, the frog Xenopus, zebrafish and multispecies (teleost, amphibian vertebrate anatomy ontologies. Previous differences between these terminologies prevented even simple queries across databases pertaining to vertebrate morphology. This module of upper-level and specific skeletal terms currently includes 223 defined terms and 179 synonyms that integrate skeletal cells, tissues, biological processes, organs (skeletal elements such as bones and cartilages, and subdivisions of the skeletal system. The VSAO is designed to integrate with other ontologies, including the Common Anatomy Reference Ontology (CARO, Gene Ontology (GO, Uberon, and Cell Ontology (CL, and it is freely available to the community to be updated with additional terms required for research. Its structure accommodates anatomical variation among vertebrate species in development, structure, and composition. Annotation of diverse vertebrate phenotypes with this ontology will enable novel inquiries across the full spectrum of phenotypic diversity.

A unified anatomy ontology of the vertebrate skeletal system.

Science.gov (United States)

Dahdul, Wasila M; Balhoff, James P; Blackburn, David C; Diehl, Alexander D; Haendel, Melissa A; Hall, Brian K; Lapp, Hilmar; Lundberg, John G; Mungall, Christopher J; Ringwald, Martin; Segerdell, Erik; Van Slyke, Ceri E; Vickaryous, Matthew K; Westerfield, Monte; Mabee, Paula M

2012-01-01

The skeleton is of fundamental importance in research in comparative vertebrate morphology, paleontology, biomechanics, developmental biology, and systematics. Motivated by research questions that require computational access to and comparative reasoning across the diverse skeletal phenotypes of vertebrates, we developed a module of anatomical concepts for the skeletal system, the Vertebrate Skeletal Anatomy Ontology (VSAO), to accommodate and unify the existing skeletal terminologies for the species-specific (mouse, the frog Xenopus, zebrafish) and multispecies (teleost, amphibian) vertebrate anatomy ontologies. Previous differences between these terminologies prevented even simple queries across databases pertaining to vertebrate morphology. This module of upper-level and specific skeletal terms currently includes 223 defined terms and 179 synonyms that integrate skeletal cells, tissues, biological processes, organs (skeletal elements such as bones and cartilages), and subdivisions of the skeletal system. The VSAO is designed to integrate with other ontologies, including the Common Anatomy Reference Ontology (CARO), Gene Ontology (GO), Uberon, and Cell Ontology (CL), and it is freely available to the community to be updated with additional terms required for research. Its structure accommodates anatomical variation among vertebrate species in development, structure, and composition. Annotation of diverse vertebrate phenotypes with this ontology will enable novel inquiries across the full spectrum of phenotypic diversity.

A Unified Anatomy Ontology of the Vertebrate Skeletal System

Science.gov (United States)

Dahdul, Wasila M.; Balhoff, James P.; Blackburn, David C.; Diehl, Alexander D.; Haendel, Melissa A.; Hall, Brian K.; Lapp, Hilmar; Lundberg, John G.; Mungall, Christopher J.; Ringwald, Martin; Segerdell, Erik; Van Slyke, Ceri E.; Vickaryous, Matthew K.; Westerfield, Monte; Mabee, Paula M.

2012-01-01

The skeleton is of fundamental importance in research in comparative vertebrate morphology, paleontology, biomechanics, developmental biology, and systematics. Motivated by research questions that require computational access to and comparative reasoning across the diverse skeletal phenotypes of vertebrates, we developed a module of anatomical concepts for the skeletal system, the Vertebrate Skeletal Anatomy Ontology (VSAO), to accommodate and unify the existing skeletal terminologies for the species-specific (mouse, the frog Xenopus, zebrafish) and multispecies (teleost, amphibian) vertebrate anatomy ontologies. Previous differences between these terminologies prevented even simple queries across databases pertaining to vertebrate morphology. This module of upper-level and specific skeletal terms currently includes 223 defined terms and 179 synonyms that integrate skeletal cells, tissues, biological processes, organs (skeletal elements such as bones and cartilages), and subdivisions of the skeletal system. The VSAO is designed to integrate with other ontologies, including the Common Anatomy Reference Ontology (CARO), Gene Ontology (GO), Uberon, and Cell Ontology (CL), and it is freely available to the community to be updated with additional terms required for research. Its structure accommodates anatomical variation among vertebrate species in development, structure, and composition. Annotation of diverse vertebrate phenotypes with this ontology will enable novel inquiries across the full spectrum of phenotypic diversity. PMID:23251424

Cadmium-109 uptake by tumors derived from Balb C/3T3 cell lines with varying degrees of the transformed phenotype

International Nuclear Information System (INIS)

Morton, K.; Alazraki, N.; Winge, D.; Lynch, R.E.

1986-01-01

To determine if tumors are rich in metallothionein, the authors measured the vivo uptake of subcutaneously-injected carrier-free cadmium-109 in tumors and in normal tissues of Balb/C mice. The tumors were grown in the mice from cultured Balb/3T3 cells transformed by the Moloney murine sarcoma virus. Uptake of cadmium-109 per gram of tissue was greatest for liver, kidney, and spleen. However, tumor uptake of cadmium-109 was markedly greater than that in blood, skeletal muscle, bones, intestine or adipose tissue. B Sephadex G-75 chromatography, the radioactivity in tumor and in liver lysates eluted with cytochrome-C, a molecule similar in molecular weight to metal-lothionein. To determine if metallothionein levels are related to the degree of malignancy of tumors, cadmium-109 uptake in the tumors from the virally-transformed cells was compared to that in tumors from non-transformed Balb/3T3 cells and two derivative chemically transformed cell lines. There was strong correlation between the substrate-independent growth in soft agarose of the four cell lines, the rate of growth of the corresponding tumors, and the amount of cadmium-109 uptake in the tumors. The authors conclude that metallothionein levels may be elevated in tumors as a function of the degree of expression of the transformed phenotype

Omega-3 Fatty Acids and Skeletal Muscle Health

Directory of Open Access Journals (Sweden)

Stewart Jeromson

2015-11-01

Full Text Available Skeletal muscle is a plastic tissue capable of adapting and mal-adapting to physical activity and diet. The response of skeletal muscle to adaptive stimuli, such as exercise, can be modified by the prior nutritional status of the muscle. The influence of nutrition on skeletal muscle has the potential to substantially impact physical function and whole body metabolism. Animal and cell based models show that omega-3 fatty acids, in particular those of marine origin, can influence skeletal muscle metabolism. Furthermore, recent human studies demonstrate that omega-3 fatty acids of marine origin can influence the exercise and nutritional response of skeletal muscle. These studies show that the prior omega-3 status influences not only the metabolic response of muscle to nutrition, but also the functional response to a period of exercise training. Omega-3 fatty acids of marine origin therefore have the potential to alter the trajectory of a number of human diseases including the physical decline associated with aging. We explore the potential molecular mechanisms by which omega-3 fatty acids may act in skeletal muscle, considering the n-3/n-6 ratio, inflammation and lipidomic remodelling as possible mechanisms of action. Finally, we suggest some avenues for further research to clarify how omega-3 fatty acids may be exerting their biological action in skeletal muscle.

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

Improving representation of nitrogen uptake, allocation, and carbon assimilation in the Community Land Model

Science.gov (United States)

Ghimire, B.; Riley, W. J.; Koven, C.

2013-12-01

Nitrogen is the most important nutrient limiting plant carbon assimilation and growth, and is required for production of photosynthetic enzymes, growth and maintenance respiration, and maintaining cell structure. The forecasted rise in plant available nitrogen through atmospheric nitrogen deposition and the release of locked soil nitrogen by permafrost thaw in high latitude ecosystems is likely to result in an increase in plant productivity. However a mechanistic representation of plant nitrogen dynamics is lacking in earth system models. Most earth system models ignore the dynamic nature of plant nutrient uptake and allocation, and further lack tight coupling of below- and above-ground processes. In these models, the increase in nitrogen uptake does not translate to a corresponding increase in photosynthesis parameters, such as maximum Rubisco capacity and electron transfer rate. We present an improved modeling framework implemented in the Community Land Model version 4.5 (CLM4.5) for dynamic plant nutrient uptake, and allocation to different plant parts, including leaf enzymes. This modeling framework relies on imposing a more realistic flexible carbon to nitrogen stoichiometric ratio for different plant parts. The model mechanistically responds to plant nitrogen uptake and leaf allocation though changes in photosynthesis parameters. We produce global simulations, and examine the impacts of the improved nitrogen cycling. The improved model is evaluated against multiple observations including TRY database of global plant traits, nitrogen fertilization observations and 15N tracer studies. Global simulations with this new version of CLM4.5 showed better agreement with the observations than the default CLM4.5-CN model, and captured the underlying mechanisms associated with plant nitrogen cycle.

Activation of the skeletal alpha-actin promoter during muscle regeneration.

Science.gov (United States)

Marsh, D R; Carson, J A; Stewart, L N; Booth, F W

1998-11-01

Little is known concerning promoter regulation of genes in regenerating skeletal muscles. In young rats, recovery of muscle mass and protein content is complete within 21 days. During the initial 5-10 days of regeneration, mRNA abundance for IGF-I, myogenin and MyoD have been shown to be dramatically increased. The skeletal alpha-actin promoter contains E box and serum response element (SRE) regulatory regions which are directly or indirectly activated by myogenin (or MyoD) and IGF-I proteins, respectively. We hypothesized that the skeletal alpha-actin promoter activity would increase during muscle regeneration, and that this induction would occur before muscle protein content returned to normal. Total protein content and the percentage content of skeletal alpha-actin protein was diminished at 4 and 8 days and re-accumulation had largely occurred by 16 days post-bupivacaine injection. Skeletal alpha-actin mRNA per whole muscle was decreased at day 8, and thereafter returned to control values. During regeneration at day 8, luciferase activity (a reporter of promoter activity) directed by -424 skeletal alpha-actin and -99 skeletal alpha-actin promoter constructs was increased by 700% and 250% respectively; however, at day 16, skeletal alpha-actin promoter activities were similar to control values. Thus, initial activation of the skeletal alpha-actin promoter is associated with regeneration of skeletal muscle, despite not being sustained during the later stages of regrowth. The proximal SRE of the skeletal alpha-actin promoter was not sufficient to confer a regeneration-induced promoter activation, despite increased serum response factor protein binding to this regulatory element in electrophoretic mobility shift assays. Skeletal alpha-actin promoter induction during regeneration is due to a combination of regulatory elements, at least including the SRE and E box.

Thyroid uptake of I-131 during anti-thyroid drug treatment

International Nuclear Information System (INIS)

Hoque, M.; Alam, F.; Haque, F.S.; Karim, M.A.; Fariduddin, M.

2004-01-01

Hyperthyroidism is a global ailment and its treatment is very promising either by ant-thyroid drug or by radioiodine. Iodine-131 uptake test is very important for evaluation of hyperthyroid in respect to its therapy and to exclude thyroiditis. This study was performed to observe the thyroid uptake pattern during intake of anti-thyroid medicine and workout the possibility to start I-131 therapy just after withdraw of antithyroid drug without waiting few days. In this study total 252 patient's I-131 uptake test is performed. Among the patient 135 (53.57%) were female, 117 (64.43%) were male. All this patients were hyperthyroid both clinically and biochemically. Thyroid uptake was taken to all patients at 24 hours after oral administration of 5 to 10 micro-curie of I -131. Uptake was taken by an uptake system and recorded as percentage uptake. These patients are grouped into three categories. Group-A-newly diagnosed cases, who have not taken antithyroid drug or I-131 therapy, there were 82 patients in this group, and their mean uptake was 37.12 ±18.5%. Group B - this group of patients were studied during intake of antithyroid medicine, there were 130 patients in this group and their mean uptake was 34.34±16.0%. Group-B patients were further divided in two sub-groups, patients having antithyroid drug for 1 to 3 weeks (group-B 1), group B1 have mean uptake 37±21% and those were taking antithyroid for 3 weeks to 2 years (group-B2), group B2 have uptake 34.34±20%. Group C- these patients are taken from those patients who had withdrawn antithyroid drug for 3 days to 3 months, there were 40 such patients. Group C further divided into two sub-group, group-C1 (stopped for 3-10 days) and group C2 (stopped for 11 days to 3 months). Group C1 had mean uptake 38±16% and group C2 had mean uptake 35±19%. From this study it is observed that Iodine-131 uptake percentage of untreated hyperthyroid; during antithyroid drug treatment and after withdraw of antithyroid drug almost

Upon the triple phase skeletal scintigraphy in traumatology

International Nuclear Information System (INIS)

Spitz, W.

1988-01-01

A broadly established indication catalogue for skeletal scintigraphy in traumatology is resulting from about 1500 skeletal scans. Aside from the exclusion of any osseous lesion, from the differentiation of uncertain X-ray findings, from the determination of the extent of osseous lesions in polytraumatic conditions and from the assessment of the relative fracture age, the follow-up after trauma and therapeutical intervention, the demonstration of battered child syndromes and of soft tissue lesions are of special importance with regard to these topics. For all that, the high sensitivity of the 3-phase skeletal scintigraphy for every enhancement of osseous turnover represents the elementary prerequisite for the employment of this non-invasive technique as an ideal screening method in traumatological diagnostics. The experiences from the past years have resulted in an increased frequency of skeletal scintigraphic studies to a similarly high level, as it is already established in the majority of institutions with respect to oncological problems, In the development of efficient and cost favourable diagnostic strategies with only little burden to the patient, skeletal scintigraphy will in future play an important role within the palette of modern skeletal diagnostics in traumatology. (orig.) [de

Skeletal Muscle Cell Induction from Pluripotent Stem Cells

Directory of Open Access Journals (Sweden)

Yusaku Kodaka

2017-01-01

Full Text Available Embryonic stem cells (ESCs and induced pluripotent stem cells (iPSCs have the potential to differentiate into various types of cells including skeletal muscle cells. The approach of converting ESCs/iPSCs into skeletal muscle cells offers hope for patients afflicted with the skeletal muscle diseases such as the Duchenne muscular dystrophy (DMD. Patient-derived iPSCs are an especially ideal cell source to obtain an unlimited number of myogenic cells that escape immune rejection after engraftment. Currently, there are several approaches to induce differentiation of ESCs and iPSCs to skeletal muscle. A key to the generation of skeletal muscle cells from ESCs/iPSCs is the mimicking of embryonic mesodermal induction followed by myogenic induction. Thus, current approaches of skeletal muscle cell induction of ESCs/iPSCs utilize techniques including overexpression of myogenic transcription factors such as MyoD or Pax3, using small molecules to induce mesodermal cells followed by myogenic progenitor cells, and utilizing epigenetic myogenic memory existing in muscle cell-derived iPSCs. This review summarizes the current methods used in myogenic differentiation and highlights areas of recent improvement.

Evaluating two-dimensional skeletal structure parameters using radiological bone morphometric analysis

International Nuclear Information System (INIS)

Asa, Kensuke; Sakurai, Takashi; Kashima, Isamu; Kumasaka, Satsuki

2005-01-01

The objectives of this study was to investigate the reliability of two-dimensional (2D) skeletal structure parameters obtained using radiological bone morphometric analysis. The 2D skeletal parameters in the regions of interest (ROIs) were measured on computed radiography (CR) images of first phalanges from racehorses, using radiological bone morphometric analysis. Cancellous bone blocks were made from the phalanges in the same position as the ROI determined on CR images. Three-dimensional (3D) trabecular parameters were measured using micro-computed tomography (μCT). The correlations between the 2D skeletal parameters and 3D trabecular parameters were evaluated in relation to the measured bone strength. The following 2D skeletal structure parameters were correlated with bone strength (r=0.61-0.69): skeletal perimeter (Sk.Pm), skeletal number (Sk.N), skeletal separation (Sk.Sp), skeletal spacing (Sk.Spac), fractal dimension (FD), and skeletal pattern factor (SkPf). The 3D trabecular structure parameters were closely correlated with bone strength (r=0.74-0.86). The 2D skeletal parameters Sk.N, Sk.Pm, FD, SkPf, and Sk.Spac were correlated with the 3D trabecular parameters (r=0.61-0.70). The 2D skeletal parameters obtained using radiological bone morphometric analysis may be useful indicators of trabecular strength. (author)

Skeletal muscle proteomic signature and metabolic impairment in pulmonary hypertension.

Science.gov (United States)

Malenfant, Simon; Potus, François; Fournier, Frédéric; Breuils-Bonnet, Sandra; Pflieger, Aude; Bourassa, Sylvie; Tremblay, Ève; Nehmé, Benjamin; Droit, Arnaud; Bonnet, Sébastien; Provencher, Steeve

2015-05-01

Exercise limitation comes from a close interaction between cardiovascular and skeletal muscle impairments. To better understand the implication of possible peripheral oxidative metabolism dysfunction, we studied the proteomic signature of skeletal muscle in pulmonary arterial hypertension (PAH). Eight idiopathic PAH patients and eight matched healthy sedentary subjects were evaluated for exercise capacity, skeletal muscle proteomic profile, metabolism, and mitochondrial function. Skeletal muscle proteins were extracted, and fractioned peptides were tagged using an iTRAQ protocol. Proteomic analyses have documented a total of 9 downregulated proteins in PAH skeletal muscles and 10 upregulated proteins compared to healthy subjects. Most of the downregulated proteins were related to mitochondrial structure and function. Focusing on skeletal muscle metabolism and mitochondrial health, PAH patients presented a decreased expression of oxidative enzymes (pyruvate dehydrogenase, p metabolism in PAH skeletal muscles. We provide evidences that impaired mitochondrial and metabolic functions found in the lungs and the right ventricle are also present in skeletal muscles of patients. • Proteomic and metabolic analysis show abnormal oxidative metabolism in PAH skeletal muscle. • EM of PAH patients reveals abnormal mitochondrial structure and distribution. • Abnormal mitochondrial health and function contribute to exercise impairments of PAH. • PAH may be considered a vascular affliction of heart and lungs with major impact on peripheral muscles.

Skeletal muscle interleukin-6 regulates metabolic factors in iWAT during HFD and exercise training

DEFF Research Database (Denmark)

Knudsen, Jakob Grunnet; Bertholdt, Lærke; Joensen, Ella

2015-01-01

in combination with exercise training (HFD ExTr) for 16 weeks. RESULTS: Total fat mass increased (P mass than HFD Floxed mice. Accordingly, iWAT glucose transporter 4 (GLUT4) protein content, 5'AMP......OBJECTIVE: To investigate the role of skeletal muscle (SkM) interleukin (IL)-6 in the regulation of adipose tissue metabolism. METHODS: Muscle-specific IL-6 knockout (IL-6 MKO) and IL-6(loxP/loxP) (Floxed) mice were subjected to standard rodent diet (Chow), high-fat diet (HFD), or HFD.......05) in HFD IL-6 MKO than HFD Floxed mice, and pyruvate dehydrogenase E1α (PDH-E1α) protein content was higher (P mass through regulation of glucose uptake capacity as well as lipogenic...

Comparative uptake of gamma-emitting fission product nuclides by plants

International Nuclear Information System (INIS)

D'souza, T.J.; Mistry, K.B.

1974-01-01

The comparative uptake of long-lived gamma-emitting fission product nuclides 106 Ru, 125 Sb, 137 Cs and 144 Ce, present in global fallout from nuclear explosions, by maize (Zea mays L) plants was examined in water culture experiments. Over identical duration of plant growth, the extent of accumulation of the radionuclides in aerial tissues was in the following decreasing order: 137 Cs >, 125 Sb >, 106 Ru > and 144 Ce. In roots, however, the retention of 144 Ce and 106 Ru was greater than that of 137 Cs and 125 Sb. Complementary studies with maize and rice (Oryza sativa L) grown on two contrasting soil types, namely, laterite and black clay loam indicated that 137 Cs uptake by plants was markedly greater than that of the other radionuclides in both soil types. Plant uptake of 106 Ru and 125 Sb was significantly higher than that of 144 Ce in the black soil. In the laterite, however, 144 Ce uptake far exceeded that of 106 Ru and 125 Sb. In general, maize removed higher amounts of the radionuclides than rice from both soil types. (author)

Measurement of skeletal muscle collagen breakdown by microdialysis

DEFF Research Database (Denmark)

Miller, B F; Ellis, D; Robinson, M M

2011-01-01

Exercise increases the synthesis of collagen in the extracellular matrix of skeletal muscle. Breakdown of skeletal muscle collagen has not yet been determined because of technical limitations. The purpose of the present study was to use local sampling to determine skeletal muscle collagen breakdown...... collagen breakdown 17–21 h post-exercise, and our measurement of OHP using GC–MS was in agreement with traditional assays....

A metabolic link to skeletal muscle wasting and regeneration

Directory of Open Access Journals (Sweden)

René eKoopman

2014-02-01

Full Text Available Due to its essential role in movement, insulating the internal organs, generating heat to maintain core body temperature, and acting as a major energy storage depot, any impairment to skeletal muscle structure and function may lead to an increase in both morbidity and mortality. In the context of skeletal muscle, altered metabolism is directly associated with numerous pathologies and disorders, including diabetes, and obesity, while many skeletal muscle pathologies have secondary changes in metabolism, including cancer cachexia, sarcopenia and the muscular dystrophies. Furthermore, the importance of cellular metabolism in the regulation of skeletal muscle stem cells is beginning to receive significant attention. Thus, it is clear that skeletal muscle metabolism is intricately linked to the regulation of skeletal muscle mass and regeneration. The aim of this review is to discuss some of the recent findings linking a change in metabolism to changes in skeletal muscle mass, as well as describing some of the recent studies in developmental, cancer and stem-cell biology that have identified a role for cellular metabolism in the regulation of stem cell function, a process termed ‘metabolic reprogramming’.

Disease-Induced Skeletal Muscle Atrophy and Fatigue

NARCIS (Netherlands)

Powers, Scott K.; Lynch, Gordon S.; Murphy, Kate T.; Reid, Michael B.; Zijdewind, Inge

2016-01-01

Numerous health problems including acute critical illness, cancer, diseases associated with chronic inflammation, and neurological disorders often result in skeletal muscle weakness and fatigue. Disease-related muscle atrophy and fatigue is an important clinical problem because acquired skeletal

The HO-1/CO system regulates mitochondrial-capillary density relationships in human skeletal muscle.

Science.gov (United States)

Pecorella, Shelly R H; Potter, Jennifer V F; Cherry, Anne D; Peacher, Dionne F; Welty-Wolf, Karen E; Moon, Richard E; Piantadosi, Claude A; Suliman, Hagir B

2015-10-15

The heme oxygenase-1 (HO-1)/carbon monoxide (CO) system induces mitochondrial biogenesis, but its biological impact in human skeletal muscle is uncertain. The enzyme system generates CO, which stimulates mitochondrial proliferation in normal muscle. Here we examined whether CO breathing can be used to produce a coordinated metabolic and vascular response in human skeletal muscle. In 19 healthy subjects, we performed vastus lateralis muscle biopsies and tested one-legged maximal O2 uptake (V̇o2max) before and after breathing air or CO (200 ppm) for 1 h daily for 5 days. In response to CO, there was robust HO-1 induction along with increased mRNA levels for nuclear-encoded mitochondrial transcription factor A (Tfam), cytochrome c, cytochrome oxidase subunit IV (COX IV), and mitochondrial-encoded COX I and NADH dehydrogenase subunit 1 (NDI). CO breathing did not increase V̇o2max (1.96 ± 0.51 pre-CO, 1.87 ± 0.50 post-CO l/min; P = not significant) but did increase muscle citrate synthase, mitochondrial density (139.0 ± 34.9 pre-CO, 219.0 ± 36.2 post-CO; no. of mitochondrial profiles/field), myoglobin content and glucose transporter (GLUT4) protein level and led to GLUT4 localization to the myocyte membrane, all consistent with expansion of the tissue O2 transport system. These responses were attended by increased cluster of differentiation 31 (CD31)-positive muscle capillaries (1.78 ± 0.16 pre-CO, 2.37 ± 0.59 post-CO; capillaries/muscle fiber), implying the enrichment of microvascular O2 reserve. The findings support that induction of the HO-1/CO system by CO not only improves muscle mitochondrial density, but regulates myoglobin content, GLUT4 localization, and capillarity in accordance with current concepts of skeletal muscle plasticity. Copyright © 2015 the American Physiological Society.

The relationship between the hypokalaemic response to adrenaline, beta-adrenoceptors, and Na(+)-K+ pumps in skeletal and cardiac muscle membranes in the rabbit

International Nuclear Information System (INIS)

Elfellah, M.S.; Reid, J.L.

1990-01-01

The hypokalaemic response to adrenaline and the involvement of beta-adrenoceptors and Na(+)-K+ pumps were investigated in control rabbits and animals chronically pretreated with adrenaline. The hypokalaemic response to acute intravenous infusion of adrenaline was significantly reduced when rabbits were chronically pretreated with adrenaline for 10 days. Chronic pretreatment of rabbits with adrenaline significantly reduced the densities for [125I]cyanopindolol and [3H]ouabain binding sites in skeletal muscle and heart. Furthermore, there was a strong positive correlation (r = 0.97, p less than 0.001) between the Bmax for ICYP and [3H]ouabain, in the rabbit heart. Ouabain-sensitive 86Rb uptake and the activity of 3-O-methylfluorescein phosphate phosphatase were used to assess the function of the Na(+)-K+ pump in skeletal and cardiac muscle. There was no significant difference in these functional indices of the Na(+)-K+ pump between the control and adrenaline-pretreated animals, in skeletal or cardiac muscle. Thus, downregulation of the [3H]ouabain binding sites did not appear to be accompanied by reduced function of the Na(+)-K+ pump. Additional investigations are required to confirm further the dissociation between the function of the pump and the ouabain binding sites

A three-dimensional analysis of skeletal and dental characteristics in skeletal class III patients with facial asymmetry.

Science.gov (United States)

Yu, Jinfeng; Hu, Yun; Huang, Mingna; Chen, Jun; Ding, Xiaoqian; Zheng, Leilei

2018-03-15

To evaluate the skeletal and dental characteristics in skeletal class III patients with facial asymmetry and to analyse the relationships among various parts of the stomatognathic system to provide a theoretical basis for clinical practice. Asymmetric cone-beam computed tomography data acquired from 56 patients were evaluated using Mimics 10.0 and 3-Matic software. Skeletal and dental measurements were performed to assess the three-dimensional differences between two sides. Pearson correlation analysis was used to determine the correlations among measurements. Linear measurements, such as ramal height, mandible body length, ramal height above the sigmoid notch (RHASN), maxillary height, condylar height, buccal and total cancellous bone thickness, and measurements of condylar size, were significantly larger on the nondeviated side than on the deviated side (P orthodontic camouflage has limitations and potential risks. A combination of orthodontics and orthognathic surgery may be the advisable choice in patients with a menton deviation greater than 4 mm. An important association between vertical skeletal disharmony and dental compensation was also observed.

Effects of administration route, dietary condition, and blood glucose level on kinetics and uptake of 18F-FDG in mice.

Science.gov (United States)

Wong, Koon-Pong; Sha, Wei; Zhang, Xiaoli; Huang, Sung-Cheng

2011-05-01

The effects of dietary condition and blood glucose level on the kinetics and uptake of (18)F-FDG in mice were systematically investigated using intraperitoneal and tail-vein injection. Dynamic PET was performed for 60 min on 23 isoflurane-anesthetized male C57BL/6 mice after intravenous (n = 11) or intraperitoneal (n = 12) injection of (18)F-FDG. Five and 6 mice in the intravenous and intraperitoneal groups, respectively, were kept fasting overnight (18 ± 2 h), and the others were fed ad libitum. Serial blood samples were collected from the femoral artery to measure (18)F-FDG and glucose concentrations. Image data were reconstructed using filtered backprojection with CT-based attenuation correction. The standardized uptake value (SUV) was estimated from the 45- to 60-min image. The metabolic rate of glucose (MRGlu) and (18)F-FDG uptake constant (K(i)) were derived by Patlak graphical analysis. In the brain, SUV and K(i) were significantly higher in fasting mice with intraperitoneal injection, but MRGlu did not differ significantly under different dietary states and administration routes. Cerebral K(i) was inversely related to elevated blood glucose levels, irrespective of administration route or dietary state. In myocardium, SUV, K(i), and MRGlu were significantly lower in fasting than in nonfasting mice for both routes of injection. Myocardial SUV and K(i) were strongly dependent on the dietary state, and K(i) did not correlate with the blood glucose level. Similar results were obtained for skeletal muscle, although the differences were not as pronounced. Intraperitoneal injection is a valid alternative route, providing pharmacokinetic data equivalent to data from tail-vein injection for small-animal (18)F-FDG PET. Cerebral K(i) varies inversely with blood glucose level, but the measured cerebral MRGlu does not correlate with blood glucose level or dietary condition. Conversely, the K(i) values of the myocardium and skeletal muscle are strongly dependent on

Is skeletal anchorage changing the limit of orthodontics?

DEFF Research Database (Denmark)

Melsen, Birte

2007-01-01

The limits for orthodontic treatment are often set by the lack of suitable anchorage. The mini-implant is used where conventional anchorage cannot be applied; not as a replacement for conventional anchorage. In patients with lack of teeth and reduced periodontium, skeletal anchorage allows...... and can be loaded immediately. The course will be addressed the following topics: Are the mini-implants replacing conventional anchorage? Why are orthodontic mini-implants necessary? The development of the skeletal anchorage systems The biological basis for the skeletal anchorage systems...... The characteristics of the different skeletal anchorage systems The insertion procedure The indications for the use of orthodontic mini-implants Treatment planning in relation to the use of mini-implants Case presentations...

Methods for the determination of skeletal muscle blood flow: development, strengths and limitations

DEFF Research Database (Denmark)

Gliemann, Lasse; Mortensen, Stefan P.; Hellsten, Ylva

2018-01-01

Since the first measurements of limb blood flow at rest and during nerve stimulation were conducted in the late 1800s, a number of methods have been developed for the determination of limb and skeletal muscle blood flow in humans. The methods, which have been applied in the study of aspects...... such as blood flow regulation, oxygen uptake and metabolism, differ in terms of strengths and degree of limitations but most have advantages for specific settings. The purpose of this review is to describe the origin and the basic principles of the methods, important aspects and requirements of the procedures....... One of the earliest methods, venous occlusion plethysmography, is a noninvasive method which still is extensively used and which provides similar values as other more direct blood flow methods such as ultrasound Doppler. The constant infusion thermodilution method remains the most appropriate...

Thyroid uptake test

International Nuclear Information System (INIS)

Ganatra, R.D.

1992-01-01

The uptake of radioiodine by the thyroid gland is altered by the iodine content of diet or drugs. American diet has a high iodine content because each slice of the white bread contains nearly 150μg of iodine due to the bleaching process employed in the production of the bread. This carrier content of iodine reduces the uptake so much, that the normal American uptakes are usually three to four times lower than the uptakes in the developing countries. The other drawback of the thyroid uptake test is that it is affected by the iodine containing drugs. Anti-diarrhoea medications are quire common in the developing countries and many of them contain iodine moiety. Without a reliable drug history, a low thyroid uptake value may lead to a misleading conclusion

Knowledge sharing in global health research - the impact, uptake and cost of open access to scholarly literature.

Science.gov (United States)

Smith, Elise; Haustein, Stefanie; Mongeon, Philippe; Shu, Fei; Ridde, Valéry; Larivière, Vincent

2017-08-29

In 1982, the Annals of Virology published a paper showing how Liberia has a highly endemic potential of Ebola warning health authorities of the risk for potential outbreaks; this journal is only available by subscription. Limiting the accessibility of such knowledge may have reduced information propagation toward public health actors who were indeed surprised by and unprepared for the 2014 epidemic. Open access (OA) publication can allow for increased access to global health research (GHR). Our study aims to assess the use, cost and impact of OA diffusion in the context of GHR. A total of 3366 research articles indexed under the Medical Heading Subject Heading "Global Health" published between 2010 and 2014 were retrieved using PubMed to (1) quantify the uptake of various types of OA, (2) estimate the article processing charges (APCs) of OA, and (3) analyse the relationship between different types of OA, their scholarly impact and gross national income per capita of citing countries. Most GHR publications are not available directly on the journal's website (69%). Further, 60.8% of researchers do not self-archive their work even when it is free and in keeping with journal policy. The total amount paid for APCs was estimated at US$1.7 million for 627 papers, with authors paying on average US$2732 per publication; 94% of APCs were paid to journals owned by the ten most prominent publication houses from high-income countries. Researchers from low- and middle-income countries are generally citing less expensive types of OA, while researchers in high-income countries are citing the most expensive OA. Although OA may help in building global research capacity in GHR, the majority of publications remain subscription only. It is logical and cost-efficient for institutions and researchers to promote OA by self-archiving publications of restricted access, as it not only allows research to be cited by a broader audience, it also augments citation rates. Although OA does not

The Effects of Temperature and CO2-induced Acidification on Skeletal Morphology of the Tropical Reef-building Coral Siderastrea siderea

Science.gov (United States)

Cobleigh, K.

2016-02-01

Coral reefs are threatened by increasing sea surface temperatures and decreasing surface seawater pH. Although numerous experimental studies have examined the effects of these global scale stressors on corals, few have quantified the effects of temperature and acidification on coral skeletal morphology. We conducted controlled laboratory experiments to investigate the effects of temperature (25, 28, 32°C) and CO2-induced ocean acidification (pCO2 = 324, 477, 604, 2553 µatm) on skeletal morphology of the highly resilient Caribbean reef-building coral Siderastrea siderea over a 95-day interval. Post-treatment S. siderea corallites from nearshore, backreef, and forereef colonies were imaged via stereo microscopy to evaluate impact of warming and acidification on corallite height and infilling. Both an increase and decrease in temperature relative to the control (i.e., near-present-day temperatures) resulted in increased corallite height but decreased skeletal infilling. In contrast, corals reared under the lowest (i.e., pre-industrial) and highest pCO2 treatments (i.e., extreme pCO2) exhibited both decreased corallite height and skeletal infilling relative to the control. We observed no difference in corallite height or infilling across reef zones, either within or across treatments. Interestingly, the warming projected for the end of the 21st century (32°C) resulted in increased corallite height and reduced corallite infilling. Acidification projected for the same interval (pCO2 = 604 µatm) also resulted in increased corallite height and decreased infilling. Collectively, our results suggest that these two global stressors will result in S. siderea corallites that are taller yet less infilled by the end of the 21st century. Changes in S. siderea arising from warming and acificiation may exacerbate observed declines in coral health across Caribbean reef systems.

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.

Forest Transpiration: Resolving Species-Specific Root Water Uptake Patterns

Science.gov (United States)

Blume, T.; Heidbuechel, I.; Simard, S.; Guntner, A.; Weiler, M.; Stewart, R. D.

2016-12-01

Transpiration and its spatio-temporal variability are still not fully understood, despite their importance for the global water cycle. This is in part due to our inability to measure transpiration comprehensively. Transpiration is usually either estimated with empirical equations based on climatic variables and crop factors, by measuring sap velocities, estimating sap wood area and scaling up to the forest stand based on a number of assumptions or by measuring the integral signal across a footprint with eddy flux towers. All these methods are focused on the cumulated loss of water to the atmosphere and do not provide information on where this water is coming from. In this study, spatio-temporal variability of root water uptake was investigated in a forest in the northeastern German lowlands. The soils are sandy and the depth of the unsaturated zone ranges from 1 to 30 m. We estimated root water uptake from different soil depths, from 0.1 m down to 2 m, based on diurnal fluctuations in soil moisture content during rain-free days. The 15 field sites cover different topographic positions and forest stands: 4 pure stands of both mature and young beech and pine and 9 mixed stands. The resulting daily data set of root water uptake shows that the forest stands differ in total amounts as well as in uptake depth distributions. Temporal dynamics of signal strength within the profile suggest a locally shifting spatial distribution of uptake that changes with water availability. The relationship of these depth-resolved uptake rates to overall soil water availability varies considerably between tree species. Using the physically-based soil hydrological model HYDRUS we investigated to what extent the observed patterns in uptake can be related to soil physical relationships alone and where tree species-specific aspects come into play. We furthermore used the model to test assumptions and estimate uncertainties of this soil moisture based estimation of plant water uptake. The

Insulin accelerates global and mitochondrial protein synthesis rates in neonatal muscle during sepsis

Science.gov (United States)

In neonatal pigs, sepsis decreases protein synthesis in skeletal muscle by decreasing translation initiation. However, insulin stimulates muscle protein synthesis despite persistent repression of translation initiation signaling. To determine whether the insulin-induced increase in global rates of m...

Skeletal stem cells in space and time

DEFF Research Database (Denmark)

Kassem, Moustapha; Bianco, Paolo

2015-01-01

The nature, biological characteristics, and contribution to organ physiology of skeletal stem cells are not completely determined. Chan et al. and Worthley et al. demonstrate that a stem cell for skeletal tissues, and a system of more restricted, downstream progenitors, can be identified in mice...

Cardiac, Skeletal, and smooth muscle mitochondrial respiration

DEFF Research Database (Denmark)

Park, Song-Young; Gifford, Jayson R; Andtbacka, Robert H I

2014-01-01

, skeletal, and smooth muscle was harvested from a total of 22 subjects (53±6 yrs) and mitochondrial respiration assessed in permeabilized fibers. Complex I+II, state 3 respiration, an index of oxidative phosphorylation capacity, fell progressively from cardiac, skeletal, to smooth muscle (54±1; 39±4; 15......±1 pmol•s(-1)•mg (-1), prespiration rates were normalized by CS (respiration...... per mitochondrial content), oxidative phosphorylation capacity was no longer different between the three muscle types. Interestingly, Complex I state 2 normalized for CS activity, an index of non-phosphorylating respiration per mitochondrial content, increased progressively from cardiac, skeletal...

Impact of blood glucose, diabetes, insulin, and obesity on standardized uptake values in tumors and healthy organs on 18F-FDG PET/CT

International Nuclear Information System (INIS)

Büsing, Karen A.; Schönberg, Stefan O.; Brade, Joachim; Wasser, Klaus

2013-01-01

Introduction: Chronically altered glucose metabolism interferes with 18 F-FDG uptake in malignant tissue and healthy organs and may therefore lower tumor detection in 18 F-FDG PET/CT. The present study assesses the impact of elevated blood glucose levels (BGL), diabetes, insulin treatment, and obesity on 18 F-FDG uptake in tumors and biodistribution in normal organ tissues. Methods: 18 F-FDG PET/CT was analyzed in 90 patients with BGL ranging from 50 to 372 mg/dl. Of those, 29 patients were diabetic and 21 patients had received insulin prior to PET/CT; 28 patients were obese with a body mass index > 25. The maximum standardized uptake value (SUV max ) of normal organs and the main tumor site was measured. Differences in SUV max in patients with and without elevated BGLs, diabetes, insulin treatment, and obesity were compared and analyzed for statistical significance. Results: Increased BGLs were associated with decreased cerebral FDG uptake and increased uptake in skeletal muscle. Diabetes and insulin diminished this effect, whereas obesity slightly enhanced the outcome. Diabetes and insulin also increased the average SUV max in muscle cells and fat, whereas the mean cerebral SUV max was reduced. Obesity decreased tracer uptake in several healthy organs by up to 30%. Tumoral uptake was not significantly influenced by BGL, diabetes, insulin, or obesity. Conclusions: Changes in BGLs, diabetes, insulin, and obesity affect the FDG biodistribution in muscular tissue and the brain. Although tumoral uptake is not significantly impaired, these findings may influence the tumor detection rate and are therefore essential for diagnosis and follow-up of malignant diseases

Primary sacrococcygeal chordoma with unusual skeletal muscle metastasis

Directory of Open Access Journals (Sweden)

Lisa Vu, MD

2014-01-01

Full Text Available Chordomas are rare neoplasms that do not often metastasize. Of the small percent that do metastasize, they very infrequently involve skeletal muscle. Only a few cases of skeletal muscle metastases have been reported in the literature. We report an unusual case of a patient with a primary sacrococcygeal chordoma who experienced a long period of remission but who subsequently developed recurrence and multiple metastatic lesions to skeletal muscles including the deltoid, triceps, and pectineus.

An analysis of correlation between occlusion classification and skeletal pattern

International Nuclear Information System (INIS)

Lu Xinhua; Cai Bin; Wang Dawei; Wu Liping

2003-01-01

Objective: To study the correlation between dental relationship and skeletal pattern of individuals. Methods: 194 cases were selected and classified by angle classification, incisor relationship and skeletal pattern respectively. The correlation of angle classification and incisor relationship to skeletal pattern was analyzed with SPSS 10.0. Results: The values of correlation index (Kappa) were 0.379 and 0.494 respectively. Conclusion: The incisor relationship is more consistent with skeletal pattern than angle classification

[Effects of lycopene on the skeletal system].

Science.gov (United States)

Sołtysiak, Patrycja; Folwarczna, Joanna

2015-02-21

Antioxidant substances of plant origin, such as lycopene, may favorably affect the skeletal system. Lycopene is a carotenoid pigment, responsible for characteristic red color of tomatoes. It is believed that lycopene may play a role in the prevention of various diseases; despite theoretical premises and results of experimental studies, the effectiveness of lycopene has not yet been clearly demonstrated in studies carried out in humans. The aim of the study was to present the current state of knowledge on the effects of lycopene on the osseous tissue in in vitro and in vivo experimental models and on the skeletal system in humans. Results of the studies indicate that lycopene may inhibit bone resorption. Favorable effects of high doses of lycopene on the rat skeletal system in experimental conditions, including the model of osteoporosis induced by estrogen deficiency, have been demonstrated. The few epidemiological and clinical studies, although not fully conclusive, suggest a possible beneficial effect of lycopene present in the diet on the skeletal system.

Dynamics of the Skeletal Muscle Secretome during Myoblast Differentiation

DEFF Research Database (Denmark)

Henningsen, Jeanette; Rigbolt, Kristoffer T G; Blagoev, Blagoy

2010-01-01

During recent years, increased efforts have focused on elucidating the secretory function of skeletal muscle. Through secreted molecules, skeletal muscle affects local muscle biology in an auto/paracrine manner as well as having systemic effects on other tissues. Here we used a quantitative...... proteomics platform to investigate the factors secreted during the differentiation of murine C2C12 skeletal muscle cells. Using triple encoding stable isotope labeling by amino acids in cell culture, we compared the secretomes at three different time points of muscle differentiation and followed the dynamics...... of the skeletal muscle as a prominent secretory organ. In addition to previously reported molecules, we identified many secreted proteins that have not previously been shown to be released from skeletal muscle cells nor shown to be differentially released during the process of myogenesis. We found 188...

Skeletal Muscle-specific G Protein-coupled Receptor Kinase 2 Ablation Alters Isolated Skeletal Muscle Mechanics and Enhances Clenbuterol-stimulated Hypertrophy.

Science.gov (United States)

Woodall, Benjamin P; Woodall, Meryl C; Luongo, Timothy S; Grisanti, Laurel A; Tilley, Douglas G; Elrod, John W; Koch, Walter J

2016-10-14

GRK2, a G protein-coupled receptor kinase, plays a critical role in cardiac physiology. Adrenergic receptors are the primary target for GRK2 activity in the heart; phosphorylation by GRK2 leads to desensitization of these receptors. As such, levels of GRK2 activity in the heart directly correlate with cardiac contractile function. Furthermore, increased expression of GRK2 after cardiac insult exacerbates injury and speeds progression to heart failure. Despite the importance of this kinase in both the physiology and pathophysiology of the heart, relatively little is known about the role of GRK2 in skeletal muscle function and disease. In this study we generated a novel skeletal muscle-specific GRK2 knock-out (KO) mouse (MLC-Cre:GRK2 fl/fl ) to gain a better understanding of the role of GRK2 in skeletal muscle physiology. In isolated muscle mechanics testing, GRK2 ablation caused a significant decrease in the specific force of contraction of the fast-twitch extensor digitorum longus muscle yet had no effect on the slow-twitch soleus muscle. Despite these effects in isolated muscle, exercise capacity was not altered in MLC-Cre:GRK2 fl/fl mice compared with wild-type controls. Skeletal muscle hypertrophy stimulated by clenbuterol, a β 2 -adrenergic receptor (β 2 AR) agonist, was significantly enhanced in MLC-Cre:GRK2 fl/fl mice; mechanistically, this seems to be due to increased clenbuterol-stimulated pro-hypertrophic Akt signaling in the GRK2 KO skeletal muscle. In summary, our study provides the first insights into the role of GRK2 in skeletal muscle physiology and points to a role for GRK2 as a modulator of contractile properties in skeletal muscle as well as β 2 AR-induced hypertrophy. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Skeletal Muscle-specific G Protein-coupled Receptor Kinase 2 Ablation Alters Isolated Skeletal Muscle Mechanics and Enhances Clenbuterol-stimulated Hypertrophy*

Science.gov (United States)

Woodall, Benjamin P.; Woodall, Meryl C.; Luongo, Timothy S.; Grisanti, Laurel A.; Tilley, Douglas G.; Elrod, John W.; Koch, Walter J.

2016-01-01

GRK2, a G protein-coupled receptor kinase, plays a critical role in cardiac physiology. Adrenergic receptors are the primary target for GRK2 activity in the heart; phosphorylation by GRK2 leads to desensitization of these receptors. As such, levels of GRK2 activity in the heart directly correlate with cardiac contractile function. Furthermore, increased expression of GRK2 after cardiac insult exacerbates injury and speeds progression to heart failure. Despite the importance of this kinase in both the physiology and pathophysiology of the heart, relatively little is known about the role of GRK2 in skeletal muscle function and disease. In this study we generated a novel skeletal muscle-specific GRK2 knock-out (KO) mouse (MLC-Cre:GRK2fl/fl) to gain a better understanding of the role of GRK2 in skeletal muscle physiology. In isolated muscle mechanics testing, GRK2 ablation caused a significant decrease in the specific force of contraction of the fast-twitch extensor digitorum longus muscle yet had no effect on the slow-twitch soleus muscle. Despite these effects in isolated muscle, exercise capacity was not altered in MLC-Cre:GRK2fl/fl mice compared with wild-type controls. Skeletal muscle hypertrophy stimulated by clenbuterol, a β2-adrenergic receptor (β2AR) agonist, was significantly enhanced in MLC-Cre:GRK2fl/fl mice; mechanistically, this seems to be due to increased clenbuterol-stimulated pro-hypertrophic Akt signaling in the GRK2 KO skeletal muscle. In summary, our study provides the first insights into the role of GRK2 in skeletal muscle physiology and points to a role for GRK2 as a modulator of contractile properties in skeletal muscle as well as β2AR-induced hypertrophy. PMID:27566547

Correlation of chronological, skeletal, and dental age in North Indian population

Directory of Open Access Journals (Sweden)

Madhurima Nanda

2017-01-01

Full Text Available Aim and Objectives: The aim of the study was to find out the correlation between chronological, dental, and skeletal age. Materials and Methods: Lateral cephalograms and orthopantomograms of 100 subjects of age ranging 9–14 years were obtained for the estimation of skeletal and dental age. Dental age was assessed using Demirjian's method; skeletal age was assessed using the new improved version of the cervical vertebral maturation method given by Baccetti, Franchi, and McNamara. Statistical analysis was carried out. Student's t-test and Spearman's coefficient correlation were used to assess the relation between chronological, skeletal, and dental age. Results: The Spearman's correlation coefficient was 0.777 (P < 0.001 between chronological and dental age, 0.516 (P < 0.001 between chronological and skeletal age, and 0.563 (P < 0.001 between dental and skeletal age. Conclusion: There is a good correlation between chronological and dental age in North Indian population which was higher for males as compared to females. A moderate correlation was found between chronological and skeletal age as well as between dental and skeletal age.

Plant uptake of dual-labeled organic N biased by inorganic C uptake

DEFF Research Database (Denmark)

Rasmussen, Jim; Sauheitl, Leopold; Eriksen, Jørgen

2010-01-01

glycine or CO2-3 , but found no differences in uptake rates between these C-sources. The uptake of inorganic C to the shoot tissue was higher for maize grown in full light compared to shading, which indicates a passive uptake of inorganic C with water. We conclude that uptake of inorganic C produced...

Molecular Signals and Skeletal Muscle Adaptation to Exercise

Directory of Open Access Journals (Sweden)

Mark Wilson

2013-09-01

Full Text Available The phenotypic plasticity of skeletal muscle affords a considerable degree of adaptability not seen in other bodily tissues. The mechanical properties of skeletal muscle are highly dependent on loading conditions. The extent of skeletal muscle plasticity is distinctly highlighted by a loss of muscle mass, or atrophy, after a period of reduced weight-bearing activity, for example during periods of extended bed rest, space flight and in spinal cord injury. On the other hand, increased mechanical loading, or resistance training, induces muscle growth, or hypertrophy. Endurance exercise performance is also dependent on the adaptability of skeletal muscle, especially muscles that contribute to posture, locomotion and the mechanics of breathing.  However, the molecular pathways governing skeletal muscle adaptations are yet to be satisfactorily delineated and require further investigation. Researchers in the areas of exercise physiology, physiotherapy and sports medicine are endeavoring to translate experimental knowledge into effective, innovative treatments and regimens in order to improve physical performance and health in both elite athletes and the general community. The efficacy of the translation of molecular biological paradigms in experimental exercise physiology has long been underappreciated. Indeed, molecular biology tools can now be used to answer questions regarding skeletal muscle adaptation in response to exercise and provide new frameworks to improve physical performance. Furthermore, transgenic animal models, knockout animal models and in vivo studies provide tools to test questions concerned with how exercise initiates adaptive changes in gene expression. In light of these perceived deficiencies, an attempt is made here to elucidate the molecular mechanisms of skeletal muscle adaptation to exercise. An examination will be made of the functional capacity of skeletal muscle to respond to a variety of exercise conditions, namely

Molecular Signals and Skeletal Muscle Adaptation to Exercise

Directory of Open Access Journals (Sweden)

Mark Wilson

2013-08-01

Full Text Available The phenotypic plasticity of skeletal muscle affords a considerable degree of adaptability not seen in other bodily tissues. The mechanical properties of skeletal muscle are highly dependent on loading conditions. The extent of skeletal muscle plasticity is distinctly highlighted by a loss of muscle mass, or atrophy, after a period of reduced weight-bearing activity, for example during periods of extended bed rest, space flight and in spinal cord injury. On the other hand, increased mechanical loading, or resistance training, induces muscle growth, or hypertrophy. Endurance exercise performance is also dependent on the adaptability of skeletal muscle, especially muscles that contribute to posture, locomotion and the mechanics of breathing. However, the molecular pathways governing skeletal muscle adaptations are yet to be satisfactorily delineated and require further investigation. Researchers in the areas of exercise physiology, physiotherapy and sports medicine are endeavoring to translate experimental knowledge into effective, innovative treatments and regimens in order to improve physical performance and health in both elite athletes and the general community. The efficacy of the translation of molecular biological paradigms in experimental exercise physiology has long been underappreciated. Indeed, molecular biology tools can now be used to answer questions regarding skeletal muscle adaptation in response to exercise and provide new frameworks to improve physical performance. Furthermore, transgenic animal models, knockout animal models and in vivo studies provide tools to test questions concerned with how exercise initiates adaptive changes in gene expression. In light of these perceived deficiencies, an attempt is made here to elucidate the molecular mechanisms of skeletal muscle adaptation to exercise. An examination will be made of the functional capacity of skeletal muscle to respond to a variety of exercise conditions, namely

Unusual Features of Extraarticular Skeletal Tuberculosis: New Classification and Differential Diagnosis

International Nuclear Information System (INIS)

Kim, Kun Sang; Park, Soo Soung

1983-01-01

Twenty two cases of extra articular skeletal tuberculosis which showed unusual radiological features are reported and classified into several categories with discussion on the differential diagnosis. Radiological patterns of skeletal tuberculosis is so variable that with any kind of skeletal changes the possibility of the skeletal tuberculosis should not be excluded between of lack of its classical patterns.

Purinergic receptors expressed in human skeletal muscle fibres

DEFF Research Database (Denmark)

Bornø, A; Ploug, Thorkil; Bune, L T

2012-01-01

distribution of purinergic receptors in skeletal muscle fibres. We speculate that the intracellular localization of purinergic receptors may reflect a role in regulation of muscle metabolism; further studies are nevertheless needed to determine the function of the purinergic system in skeletal muscle cells.......Purinergic receptors are present in most tissues and thought to be involved in various signalling pathways, including neural signalling, cell metabolism and local regulation of the microcirculation in skeletal muscles. The present study aims to determine the distribution and intracellular content...... of purinergic receptors in skeletal muscle fibres in patients with type 2 diabetes and age-matched controls. Muscle biopsies from vastus lateralis were obtained from six type 2 diabetic patients and seven age-matched controls. Purinergic receptors were analysed using light and confocal microscopy...

Global Warming: Physics and Facts

International Nuclear Information System (INIS)

Levi, B.G.; Hafemeister, D.; Scribner, R.

1992-01-01

This report contains papers on: A tutorial on global atmospheric energetics and the greenhouse effect; global climate models: what and how; comparison of general circulation models; climate and the earth's radiation budget; temperature and sea level change; short-term climate variability and predictions; the great ocean conveyor; trace gases in the atmosphere: temporal and spatial trends; the geochemical carbon cycle and the uptake of fossil fuel CO 2 ; forestry and global warming; the physical and policy linkages; policy implications of greenhouse warming; options for lowering US carbon dioxide emissions; options for reducing carbon dioxide emissions; and science and diplomacy: a new partnership to protect the environment

Health Occupations Module. The Skeletal System--I.

Science.gov (United States)

Temple Univ., Philadelphia, PA. Div. of Vocational Education.

This module on the skeletal system is one of eight modules designed for individualized instruction in health occupations education programs at both the secondary and postsecondary levels. This module contains an introduction to the module topic, three objectives (e.g., define the skeletal system and list its functions), and three learning…

The essence of biophysical cues in skeletal muscle tissue engineering

NARCIS (Netherlands)

Langelaan, M.L.P.

2010-01-01

Skeletal muscle is an appealing topic for tissue engineering because of its variety in applications. Evidently, tissue engineered skeletal muscle can be used in the field of regenerative medicine to repair muscular defects or dystrophies. Engineered skeletal muscle constructs can also be used as a

Role of Akirin in Skeletal Myogenesis

Directory of Open Access Journals (Sweden)

Dingbiao Long

2013-02-01

Full Text Available Akirin is a recently discovered nuclear factor that plays an important role in innate immune responses. Beyond its role in innate immune responses, Akirin has recently been shown to play an important role in skeletal myogenesis. In this article, we will briefly review the structure and tissue distribution of Akirin and discuss recent advances in our understanding of its role and signal pathway in skeletal myogenesis.

On the relations between the oceanic uptake of CO2 and its carbon isotopes

International Nuclear Information System (INIS)

Heimann, M.; Maier-Reimer, E.

1994-01-01

The recent proposals to estimate the oceanic uptake of CO 2 by monitoring the oceanic change in 13 C/ 12 C isotope ratio or the air-sea 13 C/ 12 C isotopic disequilibrium is reviewed. Because the history of atmospheric CO 2 and 13 CO 2 since preindustrial times is almost the same, the oceanic penetration depth of both tracers must be the same. This dynamic constraint permits the establishment of yet a third method to estimate the global ocean uptake of CO 2 from 13 C measurements. Using available observations in conjunction with canonical values for the global carbon cycle parameters the three methods yield inconsistent oceanic CO 2 uptake rates for the time period 1970-1990, ranging from 0 to over 3 GtC year -1 . However, uncertainties in the available carbon cycle data must be taken into account. Using a non-linear estimation procedure, a consistent scenario with an oceanic CO 2 uptake rate of 2.2±0.8 GtC year -1 can be established. The method also permits an investigation of the sensitivities of the different approaches. An analysis of the results of two three-dimensional simulations with the Hamburg Model of the Oceanic Carbon Cycle shows that the 13 C isotope indeed tracks the oceanic penetration of anthropogenic CO 2 . Because of its different time history, bomb produced radiocarbon, as measured at the time of GEOSECS, correlates much less well to excess carbon. (orig.)

Exercise Training-Induced Adaptations Associated with Increases in Skeletal Muscle Glycogen Content

Science.gov (United States)

Manabe, Yasuko; Gollisch, Katja S.C.; Holton, Laura; Kim, Young–Bum; Brandauer, Josef; Fujii, Nobuharu L.; Hirshman, Michael F.; Goodyear, Laurie J.

2012-01-01

Chronic exercise training results in numerous skeletal muscle adaptations, including increases in insulin sensitivity and glycogen content. To understand the mechanism for increased muscle glycogen, we studied the effects of exercise training on glycogen regulatory proteins in rat skeletal muscle. Female Sprague Dawley rats performed voluntary wheel running for 1, 4, or 7 weeks. After 7 weeks of training, insulin-stimulated glucose uptake was increased in epitrochlearis muscle. Compared to sedentary control rats, muscle glycogen did not change after 1 week of training, but increased significantly after 4 and 7 weeks. The increases in muscle glycogen were accompanied by elevated glycogen synthase activity and protein expression. To assess the regulation of glycogen synthase, we examined its major activator, protein phosphatase 1 (PP1), and its major deactivator, glycogen synthase kinase 3 (GSK3). Consistent with glycogen synthase activity, PP1 activity was unchanged after 1 week of training but significantly increased after 4 and 7 weeks of training. Protein expression of RGL(GM), another regulatory PP1 subunit, significantly decreased after 4 and 7 weeks of training. Unlike PP1, GSK3 phosphorylation did not follow the pattern of glycogen synthase activity. The ~40% decrease in GSK-3α phosphorylation after 1 week of exercise training persisted until 7 weeks and may function as a negative feedback to elevated glycogen. Our findings suggest that exercise training-induced increases in muscle glycogen content could be regulated by multiple mechanisms including enhanced insulin sensitivity, glycogen synthase expression, allosteric activation of glycogen synthase and PP1activity. PMID:23206309

Membranous lipodystrophy: skeletal findings on CT and MRI

Energy Technology Data Exchange (ETDEWEB)

Nwawka, O.K.; Schneider, Robert; Mintz, Douglas N. [Hospital for Special Surgery, Department of Radiology and Imaging, New York, NY (United States); Bansal, Manjula [Hospital for Special Surgery, Department of Pathology and Laboratory Medicine, New York, NY (United States); Lane, Joseph [Hospital for Special Surgery, Department of Orthopedic Surgery, New York, NY (United States)

2014-10-15

Membranous lipodystrophy, also known as Nasu-Hakola disease, is a rare hereditary condition with manifestations in the nervous and skeletal systems. The radiographic appearance of skeletal lesions has been well described in the literature. However, CT and MRI findings of lesions in the bone have not been documented to date. This report describes the radiographic, CT, MRI, and histopathologic skeletal findings in a case of membranous lipodystrophy. With corroborative pathologic findings, a diagnosis of membranous lipodystrophy on imaging allows for appropriate clinical management of disease manifestations. (orig.)

Skeletal traction and intramedullary nailing cost-effectiveness

African Journals Online (AJOL)

In the operative group 24 patients had union with one delayed union while in the traction group 12 patients had union, 9 with mal union and 4 delayed union. Conclusion: Intramedullary nailing is more cost-effective than skeletal traction. It met the dominant strategy, because it was significantly less costly than skeletal ...

Persistent resetting of the cerebral oxygen/glucose uptake ratio by brain activation

DEFF Research Database (Denmark)

Madsen, P L; Hasselbalch, S G; Hagemann, L P

1995-01-01

fraction of the activation-induced excess glucose uptake. These data confirm earlier reports that brain activation can induce resetting of the cerebral oxygen/glucose consumption ratio, and indicate that the resetting persists for a long period after cerebral activation has been terminated and physiologic......Global cerebral blood flow (CBF), global cerebral metabolic rates for oxygen (CMRO2), and for glucose (CMRglc), and lactate efflux were measured during rest and during cerebral activation induced by the Wisconsin card sorting test. Measurements were performed in healthy volunteers using the Kety......-Schmidt technique. Global CMRO2 was unchanged during cerebral activation, whereas global CBF and global CMRglc both increased by 12%, reducing the molar ratio of oxygen to glucose consumption from 6.0 during baseline conditions to 5.4 during activation. Data obtained in the period following cerebral activation...

mTOR as a Key Regulator in Maintaining Skeletal Muscle Mass

Directory of Open Access Journals (Sweden)

Mee-Sup Yoon

2017-10-01

Full Text Available Maintenance of skeletal muscle mass is regulated by the balance between anabolic and catabolic processes. Mammalian target of rapamycin (mTOR is an evolutionarily conserved serine/threonine kinase, and is known to play vital roles in protein synthesis. Recent findings have continued to refine our understanding of the function of mTOR in maintaining skeletal muscle mass. mTOR controls the anabolic and catabolic signaling of skeletal muscle mass, resulting in the modulation of muscle hypertrophy and muscle wastage. This review will highlight the fundamental role of mTOR in skeletal muscle growth by summarizing the phenotype of skeletal-specific mTOR deficiency. In addition, the evidence that mTOR is a dual regulator of anabolism and catabolism in skeletal muscle mass will be discussed. A full understanding of mTOR signaling in the maintenance of skeletal muscle mass could help to develop mTOR-targeted therapeutics to prevent muscle wasting.

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.

Revised budget for the oceanic uptake of anthropogenic carbon dioxide

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Sarmiento, J.L.; Sundquist, E.T.

1992-01-01

TRACER-CALIBRATED models of the total uptake of anthropogenic CO2 by the world's oceans give estimates of about 2 gigatonnes carbon per year1, significantly larger than a recent estimate2 of 0.3-0.8 Gt C yr-1 for the synoptic air-to-sea CO2 influx. Although both estimates require that the global CO2 budget must be balanced by a large unknown terrestrial sink, the latter estimate implies a much larger terrestrial sink, and challenges the ocean model calculations on which previous CO2 budgets were based. The discrepancy is due in part to the net flux of carbon to the ocean by rivers and rain, which must be added to the synoptic air-to-sea CO2 flux to obtain the total oceanic uptake of anthropogenic CO2. Here we estimate the magnitude of this correction and of several other recently proposed adjustments to the synoptic air-sea CO2 exchange. These combined adjustments minimize the apparent inconsistency, and restore estimates of the terrestrial sink to values implied by the modelled oceanic uptake.

Skeletal maturity assessment using mandibular canine calcification stages

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Vildana Džemidžić

2016-11-01

Full Text Available Objective. The aims of this study were: to investigate the relationship between mandibular canine calcification stages and skeletal maturity; and to evaluate whether the mandibular canine calcification stages may be used as a reliable diagnostic tool for skeletal maturity assessment. Materials and methods. This study included 151 subjects: 81 females and 70 males, with ages ranging from 9 to 16 years (mean age: 12.29±1.86 years. The inclusion criteria for subjects were as follows: age between 9 and 16 years; good general health without any hormonal, nutritional, growth or dental development problems. Subjects who were undergoing or had previously received orthodontic treatment were not included in this study. The calcification stages of the left permanent mandibular canine were assessed according to the method of Demirjian, on panoramic radiographs. Assessment of skeletal maturity was carried out using the cervical vertebral maturation index (CVMI, as proposed by the Hassel-Farman method, on lateral cephalograms. The correlation between the calcification stages of mandibular canine and skeletal maturity was estimated separately for male and female subjects. Results. Correlation coefficients between calcification stages of mandibular canine and skeletal maturity were 0.895 for male and 0.701 for female subjects. Conclusions. A significant correlation was found between the calcification stages of the mandibular canine and skeletal maturity. The calcification stages of the mandibular canine show a satisfactory diagnostic performance only for assessment of pre-pubertal growth phase.

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

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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.

Regulation of the sodium-potassium pump in cultured rat skeletal myotubes by intracellular sodium ions

International Nuclear Information System (INIS)

Brodie, C.; Sampson, S.R.

1989-01-01

The properties of the Na-K pump and some of the factors controlling its amount and function were studied in rat myotubes in culture. The number of Na-K pump sites was quantified by measuring the amount of [ 3 H]ouabain bound to whole-cell preparations. Activity of the pump was determined by measurement of ouabain-sensitive 86 Rb-uptake and component of membrane potential. Chronic treatment of myotubes with tetrodotoxin (TTX), which lowers [Na]i, decreased the number of Na-K pumps, the ouabain-sensitive 86Rb uptake, and the size of the electrogenic pump component of Em. In contrast, chronic treatment with either ouabain or veratridine, which increases [Na+]i, resulted in an elevated level of Na-K pump sites. This effect was blocked by inhibitors of protein synthesis. Neither rates of degradation nor affinity of pump sites in cells treated with TTX, veratridine, or ouabain differred from those in control cells. The number and activity of Na-K pump sites were unaffected by chronic elevation in [Ca]i or chronic depolarization. We conclude that alterations in the level in intracellular Na ions play the major role in regulation of Na-K pump synthesis in cultured mammalian skeletal muscle

PGC-1α-mediated adaptations in skeletal muscle

DEFF Research Database (Denmark)

Olesen, Jesper; Kiilerich, Kristian; Pilegaard, Henriette

2010-01-01

multiple pathways and functions underline the potential importance of PGC-1alpha in skeletal muscle adaptations in humans. The absence of exercise-induced PGC-1alpha-mediated gene regulation during a physical inactive lifestyle is suggested to lead to reduced oxidative capacity of skeletal muscle...... involved in angiogenesis and the anti-oxidant defence as well as to affect expression of inflammatory markers. Exercise increases PGC-1alpha transcription and potentially PGC-1alpha activity through post-translational modifications, and concomitant PGC-1alpha-mediated gene regulation is suggested...... to be an underlying mechanism for adaptations in skeletal muscle, when exercise is repeated. The current review presents some of the key findings in PGC-1alpha-mediated regulation of metabolically related, anti-oxidant and inflammatory proteins in skeletal muscle in the basal state and in response to exercise...

Gestational diabetes is characterized by reduced mitochondrial protein expression and altered calcium signaling proteins in skeletal muscle.

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Kristen E Boyle

Full Text Available The rising prevalence of gestational diabetes mellitus (GDM affects up to 18% of pregnant women with immediate and long-term metabolic consequences for both mother and infant. Abnormal glucose uptake and lipid oxidation are hallmark features of GDM prompting us to use an exploratory proteomics approach to investigate the cellular mechanisms underlying differences in skeletal muscle metabolism between obese pregnant women with GDM (OGDM and obese pregnant women with normal glucose tolerance (ONGT. Functional validation was performed in a second cohort of obese OGDM and ONGT pregnant women. Quantitative proteomic analysis in rectus abdominus skeletal muscle tissue collected at delivery revealed reduced protein content of mitochondrial complex I (C-I subunits (NDUFS3, NDUFV2 and altered content of proteins involved in calcium homeostasis/signaling (calcineurin A, α1-syntrophin, annexin A4 in OGDM (n = 6 vs. ONGT (n = 6. Follow-up analyses showed reduced enzymatic activity of mitochondrial complexes C-I, C-III, and C-IV (-60-75% in the OGDM (n = 8 compared with ONGT (n = 10 subjects, though no differences were observed for mitochondrial complex protein content. Upstream regulators of mitochondrial biogenesis and oxidative phosphorylation were not different between groups. However, AMPK phosphorylation was dramatically reduced by 75% in the OGDM women. These data suggest that GDM is associated with reduced skeletal muscle oxidative phosphorylation and disordered calcium homeostasis. These relationships deserve further attention as they may represent novel risk factors for development of GDM and may have implications on the effectiveness of physical activity interventions on both treatment strategies for GDM and for prevention of type 2 diabetes postpartum.

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.

Ocean uptake of carbon dioxide

International Nuclear Information System (INIS)

Peng, Tsung-Hung; Takahashi, Taro

1993-01-01

Factors controlling the capacity of the ocean for taking up anthropogenic C0 2 include carbon chemistry, distribution of alkalinity, pCO 2 and total concentration of dissolved C0 2 , sea-air pCO 2 difference, gas exchange rate across the sea-air interface, biological carbon pump, ocean water circulation and mixing, and dissolution of carbonate in deep sea sediments. A general review of these processes is given and models of ocean-atmosphere system based on our understanding of these regulating processes axe used to estimate the magnitude of C0 2 uptake by the ocean. We conclude that the ocean can absorb up to 35% of the fossil fuel emission. Direct measurements show that 55% Of C0 2 from fossil fuel burning remains in the atmosphere. The remaining 10% is not accounted for by atmospheric increases and ocean uptake. In addition, it is estimated that an amount equivalent to 30% of recent annual fossil fuel emissions is released into the atmosphere as a result of deforestation and farming. To balance global carbon budget, a sizable carbon sink besides the ocean is needed. Storage of carbon in terrestrial biosphere as a result of C0 2 fertilization is a potential candidate for such missing carbon sinks

Exercise Promotes Healthy Aging of Skeletal Muscle.

Science.gov (United States)

Cartee, Gregory D; Hepple, Russell T; Bamman, Marcas M; Zierath, Juleen R

2016-06-14

Primary aging is the progressive and inevitable process of bodily deterioration during adulthood. In skeletal muscle, primary aging causes defective mitochondrial energetics and reduced muscle mass. Secondary aging refers to additional deleterious structural and functional age-related changes caused by diseases and lifestyle factors. Secondary aging can exacerbate deficits in mitochondrial function and muscle mass, concomitant with the development of skeletal muscle insulin resistance. Exercise opposes deleterious effects of secondary aging by preventing the decline in mitochondrial respiration, mitigating aging-related loss of muscle mass and enhancing insulin sensitivity. This review focuses on mechanisms by which exercise promotes "healthy aging" by inducing modifications in skeletal muscle. Copyright © 2016 Elsevier Inc. All rights reserved.

Cryopreservation of human skeletal muscle impairs mitochondrial function

DEFF Research Database (Denmark)

Larsen, Steen; Wright-Paradis, C; Gnaiger, E

2012-01-01

functionality after long term cryopreservation (1 year). Skeletal muscle samples were preserved in dimethyl sulfoxide (DMSO) for later analysis. Human skeletal muscle fibres were thawed and permeabilised with saponin, and mitochondrial respiration was measured by high-resolution respirometry. The capacity...

Orthodontics-surgical combination therapy for Class III skeletal malocclusion

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M S Ravi

2012-01-01

Full Text Available The correction of skeletal Class III malocclusion with severe mandibular prognathism in an adult individual requires surgical and Othodontic combination therapy. The inter disciplinary approach is the treatment of choice in most of the skeletal malocclusions. A case report of an adult individual with Class III malocclusion, having mandibular excess in sagittal and vertical plane and treated with orthodontics,, bilateral sagittal split osteotomy and Le - Forte I osteotomy for the correction of skeletal, dental and soft tissue discrepancies is herewith presented. The surgical-orthodontic combination therapy has resulted in near-normal skeletal, dental and soft tissue relationship, with marked improvement in the facial esthetics in turn, has helped the patient to improve the self-confidence level.

Erythropoietin receptor in human skeletal muscle and the effects of acute and long-term injections with recombinant human erythropoietin on the skeletal muscle

DEFF Research Database (Denmark)

Lundby, Carsten; Hellsten, Ylva; Jensen, Mie B. F.

2008-01-01

The presence and potential physiological role of the erythropoietin receptor (Epo-R) were examined in human skeletal muscle. In this study we demonstrate that Epo-R is present in the endothelium, smooth muscle cells, and in fractions of the sarcolemma of skeletal muscle fibers. To study...... the potential effects of Epo in human skeletal muscle, two separate studies were conducted: one to study the acute effects of a single Epo injection on skeletal muscle gene expression and plasma hormones and another to study the effects of long-term (14 wk) Epo treatment on skeletal muscle structure. Subjects...... was studied in subjects (n = 8) who received long-term Epo administration, and muscle biopsies were obtained before and after. Epo treatment did not alter mean fiber area (0.84 +/- 0.2 vs. 0.72 +/- 0.3 mm(2)), capillaries per fiber (4.3 +/- 0.5 vs. 4.4 +/- 1.3), or number of proliferating endothelial cells...

Overexpression of SMPX in adult skeletal muscle does not change skeletal muscle fiber type or size.

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Einar Eftestøl

Full Text Available Mechanical factors such as stretch are thought to be important in the regulation of muscle phenotype. Small muscle protein X-linked (SMPX is upregulated by stretch in skeletal muscle and has been suggested to serve both as a transcription factor and a mechanosensor, possibly giving rise to changes in both fiber size and fiber type. We have used in vivo confocal imaging to study the subcellular localization of SMPX in skeletal muscle fibers of adult rats using a SMPX-EGFP fusion protein. The fusion protein was localized predominantly in repetitive double stripes flanking the Z-disc, and was excluded from all nuclei. This localization would be consistent with SMPX being a mechanoreceptor, but not with SMPX playing a role as a transcription factor. In vivo overexpression of ectopic SMPX in skeletal muscle of adult mice gave no significant changes in fiber type distribution or cross sectional area, thus a role of SMPX in regulating muscle phenotype remains unclear.

TAK1 regulates skeletal muscle mass and mitochondrial function

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Hindi, Sajedah M.; Sato, Shuichi; Xiong, Guangyan; Bohnert, Kyle R.; Gibb, Andrew A.; Gallot, Yann S.; McMillan, Joseph D.; Hill, Bradford G.

2018-01-01

Skeletal muscle mass is regulated by a complex array of signaling pathways. TGF-β–activated kinase 1 (TAK1) is an important signaling protein, which regulates context-dependent activation of multiple intracellular pathways. However, the role of TAK1 in the regulation of skeletal muscle mass remains unknown. Here, we report that inducible inactivation of TAK1 causes severe muscle wasting, leading to kyphosis, in both young and adult mice.. Inactivation of TAK1 inhibits protein synthesis and induces proteolysis, potentially through upregulating the activity of the ubiquitin-proteasome system and autophagy. Phosphorylation and enzymatic activity of AMPK are increased, whereas levels of phosphorylated mTOR and p38 MAPK are diminished upon inducible inactivation of TAK1 in skeletal muscle. In addition, targeted inactivation of TAK1 leads to the accumulation of dysfunctional mitochondria and oxidative stress in skeletal muscle of adult mice. Inhibition of TAK1 does not attenuate denervation-induced muscle wasting in adult mice. Finally, TAK1 activity is highly upregulated during overload-induced skeletal muscle growth, and inactivation of TAK1 prevents myofiber hypertrophy in response to functional overload. Overall, our study demonstrates that TAK1 is a key regulator of skeletal muscle mass and oxidative metabolism. PMID:29415881