311 research outputs found
0341: AMPK exerts an insulin-sensitizing effect on cardiac glucose uptake by multiple molecular mechanisms including cytoskeleton reorganization
BackgroundInsulin-resistant cardiomyocytes are characterized by a decreased ability of insulin to stimulate glucose uptake. We have previously shown that the activation of AMPK by metformin or phenformin restores insulin-sensitivity in insulin-resistant cardiomyocytes. The aim of our present work is to understand by which molecular mechanisms AMPK exerts its insulin sensitizing effect. In this study we focused on the mTOR/p70S6K pathway and on cytoskeleton reorganization. mTOR/p70S6K, which is known to be inhibited by AMPK, is able to reduce insulin signaling via a negative feedback loop involving serine phosphorylation of IRS-1. On the other hand, cytoskeleton reorganization, which is a known target of AMPK, is responsible for the translocation of the glucose transporter GLUT4 to the plasma membrane.MethodsAdult rat cardiomyocytes were primary cultured and treated with different agents including insulin, AMPK activator (phenformin), mTOR inhibitor rapamycin and/or actin cytoskeleton inhibitor latrunculin B. Glucose uptake was assessed by detritiation of 2-3H-glucose.ResultsFirst, we tested if rapamycin was able to mimic AMPK activators. Similarly to phenformin, rapamycin increased the insulin-dependent phosphorylation of Akt involved in the regulation of glucose uptake. Despite the ability of rapamycin to induce this Akt over-phosphorylation, rapamycin was not able to restore the insulin-dependent stimulation of glucose uptake like phenformin did. On the other hand, latrunculin B abolished the insulin-sensitizing action of phenformin on glucose uptake, in insulin-sensitive as well as in insulinresistant cells.Conclusionsactin cytoskeleton reorganization but not mTOR/p70S6K, is involved in the insulin-sensitizing effect of AMPK on cardiac glucose uptake. The role played by Small G proteins, known to be involved in the regulation of actin cytoskeleton is under investigation
Control of gluconeogenesis and of enzymes of glycogen metabolism in isolated rat hepatocytes. A parallel study of the effect of phenylephrine and of glucagon
Fructose-induced increase in intracellular free Mg2+ ion concentration in rat hepatocytes: relation with the enzymes of glycogen metabolism
Mutagenesis of charged residues in a conserved sequence in the 2-kinase domain of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase
The Io, Europa and Ganymede auroral footprints at Jupiter in the ultraviolet: positions and equatorial lead angles
Jupiter's satellite auroral footprints are a consequence of the interaction
between the Jovian magnetic field with co-rotating iogenic plasma and the
Galilean moons. The disturbances created near the moons propagate as Alfv\'en
waves along the magnetic field lines. The position of the moons is therefore
"Alfv\'enically" connected to their respective auroral footprint. The angular
separation from the instantaneous magnetic footprint can be estimated by the
so-called lead angle. That lead angle varies periodically as a function of
orbital longitude, since the time for the Alfv\'en waves to reach the Jovian
ionosphere varies accordingly. Using spectral images of the Main Alfv\'en Wing
auroral spots collected by Juno-UVS during the first forty-three orbits, this
work provides the first empirical model of the Io, Europa and Ganymede
equatorial lead angles for the northern and southern hemispheres. Alfv\'en
travel times between the three innermost Galilean moons to Jupiter's northern
and southern hemispheres are estimated from the lead angle measurements. We
also demonstrate the accuracy of the mapping from the Juno magnetic field
reference model (JRM33) at the completion of the prime mission for M-shells
extending to at least 15RJ . Finally, we shows how the added knowledge of the
lead angle can improve the interpretation of the moon-induced decametric
emissions.Comment: 20 pages, 8 figures, Accepted for publication in Journal of
Geophysical Research: Space Physics on 20 April 202
Cytosolic PLA2 is required for CTL-mediated immunopathology of celiac disease via NKG2D and IL-15
IL-15 and NKG2D promote autoimmunity and celiac disease by arming cytotoxic T lymphocytes (CTLs) to cause tissue destruction. However, the downstream signaling events underlying these functional properties remain unclear. Here, we identify cytosolic phospholipase A2 (cPLA2) as a central molecule in NKG2D-mediated cytolysis in CTLs. Furthermore, we report that NKG2D induces, upon recognition of MIC+ target cells, the release of arachidonic acid (AA) by CTLs to promote tissue inflammation in association with target killing. Interestingly, IL-15, which licenses NKG2D-mediated lymphokine killer activity in CTLs, cooperates with NKG2D to induce cPLA2 activation and AA release. Finally, cPLA2 activation in intraepithelial CTLs of celiac patients provides an in vivo pathophysiological dimension to cPLA2 activation in CTLs. These results reveal an unrecognized link between NKG2D and tissue inflammation, which may underlie the emerging role of NKG2D in various immunopathological conditions and define new therapeutic targets
Training during the COVID-19 lockdown : knowledge, beliefs, and practices of 12,526 athletes from 142 countries and six continents
OBJECTIVE Our objective was to explore the training-related knowledge, beliefs, and practices of athletes and the influence of
lockdowns in response to the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome
coronavirus 2 (SARS-CoV-2).
METHODS Athletes (n = 12,526, comprising 13% world class, 21% international, 36% national, 24% state, and 6% recreational)
completed an online survey that was available from 17 May to 5 July 2020 and explored their training behaviors (training
knowledge, beliefs/attitudes, and practices), including specific questions on their training intensity, frequency, and session
duration before and during lockdown (March–June 2020).
RESULTS Overall, 85% of athletes wanted to “maintain training,” and 79% disagreed with the statement that it is “okay to not
train during lockdown,” with a greater prevalence for both in higher-level athletes. In total, 60% of athletes considered “coaching
by correspondence (remote coaching)” to be sufficient (highest amongst world-class athletes). During lockdown, < 40%
were able to maintain sport-specific training (e.g., long endurance [39%], interval training [35%], weightlifting [33%], most (83%) training for “general fitness and health maintenance” during lockdown. Athletes trained alone (80%) and focused
on bodyweight (65%) and cardiovascular (59%) exercise/training during lockdown. Compared with before lockdown, most
athletes reported reduced training frequency (from between five and seven sessions per week to four or fewer), shorter training
sessions (from ≥ 60 to < 60 min), and lower sport-specific intensity (~ 38% reduction), irrespective of athlete classification.
CONCLUSIONS COVID-19-related lockdowns saw marked reductions in athletic training specificity, intensity, frequency, and
duration, with notable within-sample differences (by athlete classification). Higher classification athletes had the strongest
desire to “maintain” training and the greatest opposition to “not training” during lockdowns. These higher classification
athletes retained training specificity to a greater degree than others, probably because of preferential access to limited training
resources. More higher classification athletes considered “coaching by correspondence” as sufficient than did lower
classification athletes. These lockdown-mediated changes in training were not conducive to maintenance or progression of
athletes’ physical capacities and were also likely detrimental to athletes’ mental health. These data can be used by policy
makers, athletes, and their multidisciplinary teams to modulate their practice, with a degree of individualization, in the
current and continued pandemic-related scenario. Furthermore, the data may drive training-related educational resources
for athletes and their multidisciplinary teams. Such upskilling would provide athletes with evidence to inform their training
modifications in response to germane situations (e.g., COVID related, injury, and illness).A specific funding was provided by the National Sports Institute
of Malaysia for this study.The National Sports Institute of Malaysia.https://www.springer.com/journal/40279am2023Sports Medicin
- …