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Rôles des polyamines dans l’action anabolique des androgènes?

02/04/2019 | Etudes sur les hormones et Etudes Compléments alimentaires


Expression of Genes that Comprise the Core Molecular Clock are Altered in the Atrophied Skeletal Muscle by Androgen Deprivation
Michael L Rossetti     The FASEB Journal       1 Apr 2019Abstract Number:579.1

Skeletal muscle atrophy increases the risk of morbidity and mortality during various pathological conditions. In males, a decrease in the production and/or bioavailability of androgens (termed hypogonadism) directly contributes to muscle atrophy during various pathological conditions. While it is known that androgens prevent muscle atrophy, the mechanism(s) by which androgens mediate this effect are largely undefined. Our laboratory previously showed that mitochondrial turnover is enhanced in the tibialis anterior (TA) muscle of mice by androgen deprivation induced by castration surgery, and the magnitude of turnover was related to the degree of muscle atrophy.

These data suggest that potentially dysfunctional mitochondria contribute to the muscle atrophy observed following androgen deprivation. To gain a better understanding of that factors that might contribute to changes in mitochondrial quality control during androgen deprived conditions, we subjected total RNA from the TA of sham and castrated mice to microarray analysis. This unbiased approach identified significant changes in expression of genes that comprise the core molecular clock. qRT-PCR confirmed that expression of Brain and Muscle Arntl 1 (Bmal1) was decreased, while expression of Period 1, Period 2, and Period 3 (Per1, 2, & 3) were increased in the TA of castrated mice. When measured across a diurnal cycle, the change in expression of Bmal1, Per1, and Per2 exhibited reduced amplitude under androgen-deprived conditions. Interestingly, strong relationships were observed between the castration-mediated changes of core clock components and the measures of mitochondrial turnover. Specifically, Bmal1 expression was directly related to BCL2/adenovirus E1B 19 kDA protein-interacting protein 3 (BNIP3) protein content (R2 = 0.88), and the expression of core clock components were also directly related to the content of various mitochondrial proteins.

Expression of core clock components were also related to the autophagy marker, p62, and the mass of the TA. Ex post facto analysis of the microarray also identified changes in genes regulating polyamine biosynthesis. As polyamines are known to alter core clock function, we determined whether androgen deprivation altered polyamine content. While castration did not alter Spermine content, there was a significant reduction in the content of Spermidine in the TA of castrated mice.

Overall, these data suggest that reduced Spermidine concentrations may contribute to alterations in the core molecular clock in the skeletal muscle under androgen-deprived conditions, which may in turn contribute to reduced mitochondrial quality control and subsequent muscle atrophy

Quelle efficacité du papier pH pour mesurer l’acidité du sang?

02/04/2019 | Etudes Compléments alimentaires


Accuracy of pH Measurements in Blood-Free Balanced Salt Solutions with and without Bovine Serum Albumin—with Four Devices (ABL80, i-STAT®, pH Paper, and pH Probe)
Josephine E. Hees       The FASEB Journal               1 Apr 2019Abstract Number:544.1

Accurate and precise measurements are vital in research. Discrepancies between the actual values and values measured by a device can have serious implications on the design and results of an experiment. Thus, it is critical to know what devices provide reliable values. The aim of this study was to compare four different devices commonly used to measure pH in the absence and presence of Bovine Serum Albumin (BSA).

A balanced salt solution (NaCl 119 mM, NaHCO3 24 mM, Glucose 5.5 mM, CaCa2 1.6 mM, KCl 4.7 mM, MgSO4 1.17 mM, NaPO4 1.18 mM) with or without 4% BSA was bubbled with different CO2 percentages (2.5%, 3.8%, 5%, 7.5 %, 10%), 30% O2 and N2 as the balance gas using a gas mixer. After a steady state pH was reached, judged by the pH probe, four samples were taken simultaneously, and 3 replicate measurements with each of the four devices were made. The devices used in this study were the ABL 80 FLEX (RADIOMETER, blood gas analyzer), VetScan i-STAT® 1, pH paper (Macherey-Nagel, pH range 6.4 – 8.0) and a pH probe (OAKTON®, pH700). Measured pH values were plotted against the expected pH values for a given concentration of CO2 according to the Henderson–Hasselbalch equation (pH = pKa + log10 ([A−]/[HA]). Linear regression ± SEM was done for each device with and without BSA and the coefficient of determination and regression coefficients were calculated. The mean and difference of each measurement by device were then calculated and used to create Bland-Altman plots (right lower corner in each panel) to assess the agreement of the measuring device with the expected pH.

Except for the pH paper, all devices showed a strong agreement with the expected pH for each CO2 percentage. The addition of BSA to the solution resulted in a trend to more acidic readings and to be even more in agreement with the expected pH for all four devices.

The blood gas analyzer, i-STAT®, and pH probe all proved to be suitable devices for use in measuring the pH of a balanced salt solution in the chosen pH range. The pH paper appeared to be unsuitable to measure the pH within physiological ranges. Additionally, throughout all measurements, the solutions with 4% BSA tended to provide even more accurate values than the solutions without BSA.

Effets directs de l’insuline sur la force?

02/04/2019 | Etudes sur les hormones


Responses to Mechanical and Chemical Stimuli are Augmented by Insulin Administration in Neurons Innervating Skeletal Muscle
Norio Hotta     The FASEB Journal               1 Apr 2019Abstract Number:540.7

Hyperinsulinemia is known to activate the sympathetic nervous system, but the underlying mechanism remains to be elucidated. Mechanical or chemical stimuli to skeletal muscle induce sympathoexcitation via group III and group IV thin-fiber afferents. Evidence suggests that insulin both facilitates translocation of molecular candidates for mechano-gated channels and activates transient receptor potential vanilloid 1 (TRPV1) channels associated with these afferent fibers. We therefore hypothesized that insulin potentiates neural responsiveness to mechanical and chemical stimuli in thin-fiber afferents and the dorsal root ganglia (DRG) that sub-serve these neurons in skeletal muscle.

We investigated the effects of insulin administration on whole-cell current responses to mechanical/chemical stimuli in DRG neurons of normal healthy mice. Further, we examined the impact of insulin on the action potential response to mechanical/chemical stimulation in thin-fiber muscle afferents of normal healthy rats.

We performed whole cell patch-clamp recordings using cultured mice DRG neurons. Mechanical stimuli to the cell surface was applied using a stimulation probe with resultant mechanically activated (MA) currents recorded. DRG neurons were also exposed to 1μM capsaicin. Using a rat muscle-nerve preparation in vitro, we applied 1) a ramp-shaped mechanical stimulation and 2) a 1μM capsaicin stimulation to the neuron’s receptive field and measured the elicited action potential utilizing single-fiber recordings.

In cultured DRG neurons, insulin (500 mU) reduced mechanical threshold from 3.6 ± 0.4 to 2.6 ± 0.3 steps (n=17, P<0.05) and increased MA current from −93±12 to −190±43 pA (n=16, P<0.05). These changes were blocked by pretreatment with the insulin receptor inhibitor GSK1838705. Likewise, the total charge transfer induced by capsaicin activated current (fold change from baseline) was significantly higher after insulin administration (3.3±1.2, n=5) than that of control (0.5±0.2, n=6). Again, this difference was prevented by pretreatment with GSK1838705. In the muscle-nerve preparation, the mechanical threshold of thin-fiber muscle afferents was significantly decreased 10 min after insulin injection (500 mU) from 66±16 to 28±12 mN (n=10, P<0.05). This decrease was eliminated by insulin receptor blockade via GSK1838705. Insulin administration also significantly increased the response magnitude to 1μM capsaicin (from 0.05±0.08 Hz before insulin to 0.70±0.40 Hz after insulin, n=5, P<0.05).

The data demonstrate that insulin sensitizes thin fiber afferents and DRG neurons innervating skeletal muscle. Further, these findings suggest that hyperinsulinemia may induce sympathoexcitation via augmentations in the responsiveness of mechano-gated channels and TRPV1 receptors on skeletal muscle thin-fiber afferents.

Effets du neural gliding sur la souplesse?

30/03/2019 | Echauffement et blessures



K. SMITH AND A. WALDHELM     Journal of Strength and Conditioning Research   VOLUME 33 | NUMBER 2 | FEBRUARY 2019 | e73
University of South Alabama

Introduction: The pre-activity warm-up is a very important
aspect in preparation for competitive sports. Prior research
has demonstrated the ability of a warm-up to influence flexibility, strength and power. Neural gliding is a fairly new intervention used in rehabilitation to improve muscle flexibility and joint
mobility of individuals with musculoskeletal and neuromuscular
injuries but the use of neural gliding in sports performance is

Purpose: The objective of this study is to compare the
effects of neural gliding and dynamic stretching exercises on
hamstring flexibility and athletic performance in collegiate basketball players.

Methods: Eight-teen NCAA Division II basketball players (8 males, 10 females; age: 18.1 6 0.24; height:
1.78 6 0.09 m; weight: 60.0 6 17.2 kg) volunteered for the
study. Data was collect during a single session and block
assignment was used with 9 individuals (4 males, 5 females)
in each group: neural gliding and dynamic stretching. Before
testing each subject performed the same 5 minute warm-up
which included jogging, running and sprinting. Pre-and postintervention testing included bilateral hamstring flexibility using
the active straight leg test, 10 and 40-yard dash, countermovement vertical jump, and 20-yard shuttle run. Between testing
the participants performed a 5 minute exercise protocol which
included bilateral sciatic nerve gliding or a dynamic lower
extremity stretching program. Multiple 2 3 2 (time by group)
repeated measures ANOVAs with p # 0.05 was used to examine differences.

Results: The results did not show a significant
time by group interactions for all 6 measurements and all main
effects were insignificant except for the countermovement vertical jump (F = 15.0, p = 0.005). Post-hoc paired t tests with
Bonferroni correction (p # 0.025) did not show as significant
difference in countermovement vertical jump performance in
both the dynamic stretching (p = 0.250) or the neural gliding
group (p = 0.107).

Conclusions: The results demonstrate that
both neural gliding and dynamic stretching exercises did not
have a significant effect on hamstring flexibility or 4 athletic
performance tests.

Practical Applications: Neural gliding can
be used as part of the pre-participation warm-up without a negative effect on athletic performance, but more research is needed
to truly determine if neural gliding should be part of a warm-up.

Régulation des ribosomes dans l’hypertrophie?

22/03/2019 | Etudes Musculation


Regulation of Ribosome Biogenesis During Skeletal Muscle Hypertrophy
Kim, Hyo-Gun         Exercise and Sport Sciences Reviews: April 2019 - Volume 47 - Issue 2 - p 91–97

An increase in ribosomal capacity is a hallmark of the hypertrophying muscle. We review evidence demonstrating that transcription of ribosomal RNA genes is necessary for the increase in ribosomal capacity, and this is critical for muscle growth in human and animal models of hypertrophy.

Hyperplasie musculaire pour la croissance?

22/03/2019 | Etudes Musculation


Muscle Fiber Splitting Is a Physiological Response to Extreme Loading in Animals
Murach, Kevin A           Exercise and Sport Sciences Reviews: April 2019 - Volume 47 - Issue 2 - p 108–115

Skeletal muscle fiber branching and splitting typically is associated with damage and regeneration and is considered pathological when observed during loading-induced hypertrophy. We hypothesize that fiber splitting is a nonpathological component of extreme loading and hypertrophy, which is primarily supported by evidence in animals, and propose that the mechanisms and consequences of fiber splitting deserve further exploration.

La follistatine agit aussi sur l’insuline

06/03/2019 | Etudes sur les hormones


Mechanisms involved in follistatin-induced increased insulin action in skeletal muscle
Xiuquing Han     bioRxiv posted 5 March 2019

Background: Skeletal muscle wasting is often associated with insulin resistance. A major regulator of muscle mass is the transforming growth factor beta (TGF-beta) superfamily, including activin A, which causes atrophy. TGF-beta superfamily ligands also negatively regulate insulin-sensitive proteins, but whether this pathway contributes to insulin action remains to be determined.

Methods: To elucidate if TGF-beta superfamily ligands regulate insulin action we used an adeno-associated virus gene editing approach to overexpress the activin A inhibitor, follistatin (Fst288) in mouse muscle of lean and diet-induced obese mice. We determined basal and insulin-stimulated 2 deoxy-glucose uptake using isotopic tracers in vivo. Furthermore, to evaluate whether circulating Fst and activin A concentrations are associated with obesity, insulin resistance, and weight loss in humans we analysed serum from morbidly obese subjects before, 1 week, and 1 year after Roux-en-Y gastric bypass (RYGB).

Results: Fst288 muscle overexpression markedly increased in vivo insulin-stimulated (but not basal) glucose uptake (+75 percent) and increased protein expression and intracellular insulin signalling of AKT, TBC1D4, PAK1, and p70S6K. Importantly, Fst288 completely normalized muscle glucose uptake in insulin-resistant diet-induced obese mice. RYGB surgery doubled circulating Fst and reduced Activin A (-24 percent) concentration 1 week after surgery before any significant weight loss in morbidly obese normoglycemic patients, while major weight loss after 1 year did not further change the concentrations.

Conclusions: We here present evidence that Fst is a potent regulator of insulin action in muscle and in addition to AKT and p70S6K, we identify TBC1D1, TBC1D4 and PAK1 as Fst targets. A possible role for Fst in regulating glycemic control is suggested because circulating Fst more than doubled post RYGB surgery, a treatment that markedly improved insulin sensitivity. These findings demonstrate the therapeutic potential of inhibiting TGF-beta superfamily ligands to improve insulin action and Fst s relevance to insulin resistant conditions in mice and humans.

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