Audrey Ginion

Catholic University of Louvain, Лувен-ла-Нев, Walloon, Belgium

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Publications (27)88.95 Total impact

  • Archives of Cardiovascular Diseases Supplements 04/2015; 7(2). DOI:10.1016/S1878-6480(15)30022-7

  • Archives of Cardiovascular Diseases Supplements 04/2015; 7(2):190-191. DOI:10.1016/S1878-6480(15)30161-0

  • Diabetes & Metabolism 03/2015; 41:A26. DOI:10.1016/S1262-3636(15)30091-4 · 3.27 Impact Factor
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    ABSTRACT: AMP-activated protein kinase (AMPK), a key cellular sensor of energy, regulates metabolic homeostasis and plays a protective role in the ischemic or diabetic heart. Stimulation of cardiac glucose uptake contributes to this AMPK-mediated protection. The small molecule AMPK activator A-769662, which binds and directly activates AMPK, has recently been characterized. A-769662-dependent AMPK activation protects the heart against an ischemia/reperfusion episode but is unable to stimulate skeletal muscle glucose uptake. Here, we tried to reconcile these conflicting findings by investigating the impact of A-769662 on cardiac AMPK signaling and glucose uptake. We showed that A-769662 promoted AMPK activation resulting in the phosphorylation of several downstream targets, but was incapable of stimulating glucose uptake in cultured cardiomyocytes and perfused heart. The lack of glucose uptake stimulation can be explained by A-769662's narrow specificity, since it selectively activates cardiac AMPK heterotrimeric complexes containing α2/β1 subunits, the others being presumably required for this metabolic outcome. However, when combined with classical AMPK activators, such as metformin, phenformin, oligomycin or hypoxia, which impact AMPK heterotrimers more broadly via elevation of cellular AMP level, A-769662 induced more profound AMPK phosphorylation and subsequent glucose uptake stimulation. The synergistic effect of A-769662 under such ischemia-mimetic conditions protected cardiomyocytes against ROS production and cell death. In conclusion, despite the fact that A-769662 activates AMPK, it alone does not significantly stimulate glucose uptake. However, strikingly, its ability of potentiating the action on other AMPK activators makes it a potentially useful participant in the protective role of AMPK in the heart.
    AJP Heart and Circulatory Physiology 04/2014; 306(12). DOI:10.1152/ajpheart.00965.2013 · 3.84 Impact Factor

  • Archives of Cardiovascular Diseases Supplements 04/2014; 6:57. DOI:10.1016/S1878-6480(14)71419-3
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    ABSTRACT: Background It was demonstrated that branched-chain amino acids like leucine induce insulin resistance in muscle and adipose tissues. The mechanism proposed to explain leucine action involves mTOR/p70S6K signaling. This pathway can be activated by leucine and is implicated in the stimulation of an insulin negative feedback loop. Knowing that insulin-resistance participates in diabetic cardiomyopathy, we were interested in studying leucine effect in cardiomyocytes. Methods Primary cultured adult rat cardiomyocytes were pretreated with different concentrations of leucine (from 1 to 10 mM) during different periods of time (up to 20h) before being exposed to insulin (3x10−9 M, 30 min). Results In absence of leucine, insulin induced a 6-fold increase in glucose uptake (0.31+/−0.04 vs. 0.05+/−0.01 μmoles/mg.h). This correlated with the increase in phosphorylation state of PKB and AS160, both known to regulate glucose transport downstream of insulin. Pre-incubation with leucine for 1 h stimulated mTOR/p70S6K pathway resulting in the inhibiting phosphorylation of IRS-1 located in the proximal insulin signaling pathway. This is accompanied by a significant decrease in PKB and AS160 phosphorylation but, surprisingly, insulin-stimulated glucose uptake was preserved (0.31+/–0.05 μmoles/mg.h). On the other hand, a longer incubation (14h) with leucine induced a drastic decrease in glucose transport (0.056+/–0.01 μmoles/mg.h). The mTOR/p70S6K inhibitor rapamycin did not prevent this inhibition. Moreover, the non-metabolized leucine analog BCH was able to stimulate mTOR/p70S6K pathway but had no effect on the insulin-mediated stimulation of glucose uptake. By contrast, intermediates of leucine catabolism, alpha-ketoisocaproate, acetoacetate and betahydroxybutyrate, inhibited glucose uptake similarly to leucine. Conclusion Leucine catabolism reduces insulin-dependent glucose transport independently of insulin signaling.
    Archives of Cardiovascular Diseases Supplements 04/2014; 6:13. DOI:10.1016/S1878-6480(14)71296-0

  • Diabetes & Metabolism 03/2014; 40:A64. DOI:10.1016/S1262-3636(14)72442-5 · 3.27 Impact Factor

  • Diabetes & Metabolism 03/2014; 40:A65. DOI:10.1016/S1262-3636(14)72444-9 · 3.27 Impact Factor
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    ABSTRACT: Mesenchymal stem cells (MSCs) are widely used for cell therapy, particularly for the treatment of ischemic heart disease. Mechanisms underlying control of their metabolism and proliferation capacity, critical elements for their survival and differentiation, have not been fully characterized. AMP-activated protein kinase (AMPK) is a key regulator known to metabolically protect cardiomyocytes against ischemic injuries and, more generally, to inhibit cell proliferation. We hypothesized that AMPK plays a role in control of MSC metabolism and proliferation.Methods and ResultsMSCs isolated from murine bone marrow exclusively expressed the AMPKα1 catalytic subunit. In contrast to cardiomyocytes, a chronic exposure of MSCs to hypoxia failed to induce cell death despite the absence of AMPK activation. This hypoxic tolerance was the consequence of a preference of MSC towards glycolytic metabolism independently of oxygen availability and AMPK signalling. On the other hand, A-769662, a well-characterized AMPK activator, was able to induce a robust and sustained AMPK activation. We showed that A-769662-induced AMPK activation inhibited MSC proliferation. Proliferation was not arrested in MSCs derived from AMPKα1-knockout mice, providing genetic evidence that AMPK is essential for this process. Among AMPK downstream targets proposed to regulate cell proliferation, we showed that neither the p70 ribosomal S6 protein kinase/eukaryotic elongation factor 2-dependent protein synthesis pathway nor p21 was involved, whereas p27 expression was increased by A-769662. Silencing p27 expression partially prevented the A-769662-dependent inhibition of MSC proliferation. MSCs resist hypoxia independently of AMPK whereas chronic AMPK activation inhibits MSC proliferation, p27 being involved in this regulation.
    Cardiovascular Research 10/2013; 101(1). DOI:10.1093/cvr/cvt227 · 5.94 Impact Factor
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    ABSTRACT: The Onecut (OC) family of transcription factors comprises three members in mammals, namely HNF-6 (or OC-1), OC-2 and OC-3. During embryonic development, these transcriptional activators control cell differentiation in pancreas, in liver and in the nervous system. Adult Hnf6 mutant mice exhibit locomotion defects characterized by hindlimb muscle weakness, abnormal gait and defective balance and coordination. Indeed, HNF-6 is required in spinal motor neurons for proper formation of the hindlimb neuromuscular junctions, which likely explain muscle weakness observed in corresponding mutant animals. The goal of the present study was to determine the cause of the balance and coordination defects in Hnf6 mutant mice. Coordination and balance deficits were quantified by rotarod and runway tests. Hnf6 mutant animals showed an increase in the fall frequency from the beam and were unable to stay on the rotarod even at low speed, indicating a severe balance and coordination deficit. To identify the origin of this abnormality, we assessed whether the development of the main CNS structure involved in the control of balance and coordination, namely the cerebellum, was affected by the absence of HNF-6. Firstly, we observed that Hnf6 was expressed transiently during the first week after birth in the Purkinje cells of wild type newborn mice. Secondly, we showed that, in Hnf6-/- mice, the organization of Purkinje cells became abnormal during a second phase of their development. Indeed, Purkinje cells were produced normally but part of them failed to reorganize as a regular continuous monolayer at the interface between the molecular and the granular layer of the cerebellum. Thus, the Onecut factor HNF-6 contributes to the reorganization of Purkinje cells during a late phase of cerebellar development.
    Molecular and Cellular Neuroscience 05/2013; 56. DOI:10.1016/j.mcn.2013.05.001 · 3.84 Impact Factor
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    ABSTRACT: Eukaryotic elongation factor 2 (eEF-2) and mammalian target of rapamycin (mTOR)-p70 ribosomal protein S6 kinase (p70S6K) signaling pathways control protein synthesis and are inhibited during myocardial ischemia. Intracellular acidosis and AMP-activated protein kinase (AMPK) activation, both occurring during ischemia, have been proposed to participate in this inhibition. We evaluated the contribution of AMPKα2, the main cardiac AMPK catalytic subunit isoform, in eEF2 and mTOR-p70S6K regulation using AMPKα2 KO mice. Hearts were perfused ex vivo with or without insulin, and then submitted or not to ischemia. Insulin pre-incubation was necessary to activate mTOR-p70S6K and evaluate their subsequent inhibition by ischemia. Ischemia decreased insulin-induced mTOR-p70S6K phosphorylation in WT and AMPKα2 KO mice to a similar extent. This AMPKα2-independent p70S6K inhibition correlated well with the inhibition of PKB/Akt, located upstream of mTOR-p70S6K and can be mimicked in cardiomyocytes by decreasing pH. By contrast, ischemia-induced inhibitory phosphorylation of eEF-2 was drastically reduced in AMPKα2 KO mice. Interestingly, AMPKα2 also played a role under normoxia. Its deletion increased the insulin-induced p70S6K stimulation. This p70S6K over-stimulation was associated with a decrease in inhibitory phosphorylation of Raptor, an mTOR partner identified as an AMPK target. In conclusion, AMPKα2 controls cardiac p70S6K under normoxia and regulates eEF-2 but not the mTOR-p70S6K pathway during ischemia. This challenges the accepted notion that mTOR-p70S6K is inhibited by myocardial ischemia mainly via an AMPK-dependent mechanism.
    Biochimica et Biophysica Acta 03/2013; 1832(6). DOI:10.1016/j.bbadis.2013.02.015 · 4.66 Impact Factor

  • Diabetes & Metabolism 03/2013; 39:A49-A50. DOI:10.1016/S1262-3636(13)71824-X · 3.27 Impact Factor
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    ABSTRACT: Il a été démontré dans le tissu adipeux et le muscle squelettique que l’insulinorésistance peut être induite par les acides aminés branchés tels que la leucine. En effet, la leucine induit l’activation de la voie mTOR/p70S6K qui phosphoryle l’IRS-1 sur les sérines 636/639. Ces phosphorylations induisent l’inhibition de l’IRS-1 et diminuent la réponse insulinique des éléments en aval comme la PKB. Une des conséquences de l’insulinorésistance est la diminution de la stimulation du captage du glucose. Dans ce travail, nous nous sommes demandé si la leucine pouvait induire une insulinorésistance dans le cœur.Matériels et méthodesDes cardiomyocytes de rat adulte en culture primaire ont été stimulés avec de l’insuline avec ou sans pré-incubation avec de la leucine. La signalisation insulinique a été évaluée par immuno-détection. Le transport du glucose a été mesuré par la détritiation du 2–3H-glucose.RésultatsEn présence d’insuline, la leucine induit une sur-phosphorylation de la p70S6K (190 ± 30 % vs insuline, p = 0,05) et des sérines 636/639 de l’IRS-1 (400 ± 80 % vs insuline, p = 0,05). Ceci a pour conséquence d’induire une diminution de 30 ± 10 % (p = 0,05) de la phosphorylation de la PKB ainsi que de son substrat, l’AS160, impliqué dans la régulation du transport du glucose. Cependant, aucune diminution de la stimulation du captage du glucose en réponse à l’insuline n’est observée en présence de leucine (contrôle 0,06 ± 0,02; insuline 0,45 ± 0,06; insuline + leucine 0,55 ± 0,07 μmoles/h. mg).Conclusion Nos résultats montrent que la leucine ne diminue pas la stimulation du transport du glucose bien qu’elle soit capable d’induire une insulinorésistance en termes de signalisation intracellulaire se traduisant par une diminution de la phosphorylation de la PKB et de l’AS160. Ceci suggère que, dans le cœur, l’axe PKB/AS160 n’est pas une étape limitante dans la stimulation du transport du glucose en réponse à l’insuline.
    Diabetes & Metabolism 03/2012; 38:A74. DOI:10.1016/S1262-3636(12)71284-3 · 3.27 Impact Factor
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    ABSTRACT: La culture de cardiomyocytes en présence d’une concentration élevée glucose stimule la production des espèces réactives (ROS) de l’oxygène via une activation de la NADPH oxidase. Le mécanisme responsable de cette activation reste peu connus. Le but de ce travail a été d’étudier les liens entre le transport et le métabolisme du glucose et l’activation de la NADPH oxidase en conditions d’hyperglycémie.Matériels et méthodesDes cardiomyocytes de rat adulte ont été mis en culture et exposés à des concentrations normales (LG, 5 mM) ou élevées de glucose (HG, 21 mM).RésultatsL’incubation des cellules en condition HG entraine une activation de Rac1 et induit la translocation de p47phox à la membrane plasmique. Ces deux phénomènes révèlent une activation de l’isoforme NOX2 de la NADPH oxidase. Il en résulte une production de ROS, un excès de mortalité cellulaire et un état d’insulino-résistance. La niveau de glycosylation (taux de résidus O-Glc-NAc) est similaire en condition HG et LG. L’inhibition de la voie des pentoses phosphate par le 6-aminonicotinamide (6-AN) contrecarre la production de ROS en réponse à l’hyperglycémie mais ne modifie pas l’activation de Rac1 et la translocation de p47phox. La modulation du transport de glucose par la phloretine ou l’insuline n’affecte que très peu la production de ROS. De manière intéressante, des analogues non-métabolisables (3-O-methyl glucose et alpha methyl glucose) du glucose reproduisent les effets toxiques de HG. L’inhibition du transporteur sodium/glucose (SGLT) par la phloridzine contrecarre l’activation de NOX2 et la génération de ROS.Conclusion La voie des pentoses phosphates est nécessaire pour l’approvisionnement de la NOX2 en NADPH mais n’est pas responsable de l’activation de celle-ci. L’activation de NOX2 ne nécessite pas la métabolisation du glucose mais est le résultat du transport de glucose par SGLT. SGLT transforme de cette manière un signal métabolique en un signal ionique.
    Diabetes & Metabolism 03/2012; 38:A74. DOI:10.1016/S1262-3636(12)71285-5 · 3.27 Impact Factor
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    ABSTRACT: Urotensin II (UII) and urocortin (UCN) are potent contributors to the physiopathology of heart failure. Our study investigated the effects of UII and UCN on the expression of myostatin (Mstn) in primary culture of adult cardiomyocytes. Adult rat cardiomyocytes were stimulated for 48 h with UII and UCN. Cell size and protein content were determined. Mstn gene expression was determined by real time quantitative polymerase chain reaction. Treatment with UII and UCN stimulates hypertrophy of adult cardiomyocytes. This effect was associated with a twofold increase of Mstn gene expression. We have established for the first time that the two hypertrophic peptides UII and UCN stimulate the expression of Mstn.
    Peptides 02/2012; 33(2):351-3. DOI:10.1016/j.peptides.2011.12.017 · 2.62 Impact Factor
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    ABSTRACT: Exposure to high glucose (HG) stimulates reactive oxygen species (ROS) production by NADPH oxidase in cardiomyocytes, but the underlying mechanism remains elusive. In this study, we have dissected the link between glucose transport and metabolism and NADPH oxidase activation under hyperglycaemic conditions. Primary cultures of adult rat cardiomyocytes were exposed to HG concentration (HG, 21 mM) and compared with the normal glucose level (LG, 5 mM). HG exposure activated Rac1GTP and induced p47phox translocation to the plasma membrane, resulting in NADPH oxidase (NOX2) activation, increased ROS production, insulin resistance, and eventually cell death. Comparison of the level of O-linked N-acetylglucosamine (O-GlcNAc) residues in LG- and HG-treated cells did not reveal any significant difference. Inhibition of the pentose phosphate pathway (PPP) by 6-aminonicotinamide counteracted ROS production in response to HG but did not prevent Rac-1 upregulation and p47phox translocation leading to NOX2 activation. Modulation of glucose uptake barely affected oxidative stress and toxicity induced by HG. More interestingly, non-metabolizable glucose analogues (i.e. 3-O-methyl-D-glucopyranoside and α-methyl-D-glucopyranoside) reproduced the toxic effect of HG. Inhibition of the sodium/glucose cotransporter SGLT1 by phlorizin counteracted HG-induced NOX2 activation and ROS production. Increased glucose metabolism by itself does not trigger NADPH oxidase activation, although PPP is required to provide NOX2 with NADPH and to produce ROS. NOX2 activation results from glucose transport through SGLT1, suggesting that an extracellular metabolic signal transduces into an intracellular ionic signal.
    Cardiovascular Research 08/2011; 92(2):237-46. DOI:10.1093/cvr/cvr230 · 5.94 Impact Factor
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    ABSTRACT: The AMP-activated protein kinase (AMPK) is known to increase cardiac insulin sensitivity on glucose uptake. AMPK also inhibits the mammalian target of rapamycin (mTOR)/p70 ribosomal S6 kinase (p70S6K) pathway. Once activated by insulin, mTOR/p70S6K phosphorylates insulin receptor substrate-1 (IRS-1) on serine residues, resulting in its inhibition and reduction of insulin signaling. AMPK was postulated to act on insulin by inhibiting this mTOR/p70S6K-mediated negative feedback loop. We tested this hypothesis in cardiomyocytes. The stimulation of glucose uptake by AMPK activators and insulin correlated with AMPK and protein kinase B (PKB/Akt) activation, respectively. Both treatments induced the phosphorylation of Akt substrate 160 (AS160) known to control glucose uptake. Together, insulin and AMPK activators acted synergistically to induce PKB/Akt overactivation, AS160 overphosphorylation, and glucose uptake overstimulation. This correlated with p70S6K inhibition and with a decrease in serine phosphorylation of IRS-1, indicating the inhibition of the negative feedback loop. We used the mTOR inhibitor rapamycin to confirm these results. Mimicking AMPK activators in the presence of insulin, rapamycin inhibited p70S6K and reduced IRS-1 phosphorylation on serine, resulting in the overphosphorylation of PKB/Akt and AS160. However, rapamycin did not enhance the insulin-induced stimulation of glucose uptake. In conclusion, although the insulin-sensitizing effect of AMPK on PKB/Akt is explained by the inhibition of the insulin-induced negative feedback loop, its effect on glucose uptake is independent of this mechanism. This disconnection revealed that the PKB/Akt/AS160 pathway does not seem to be the rate-limiting step in the control of glucose uptake under insulin treatment.
    AJP Heart and Circulatory Physiology 05/2011; 301(2):H469-77. DOI:10.1152/ajpheart.00986.2010 · 3.84 Impact Factor
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    ABSTRACT: Urocortin-1 (UCN), a member of the corticotropin-releasing factor, is a cardioprotective peptide, and is also involved in cardiac hypertrophy. The involvement of GSK-3β, a pivotal kinase in cardiac hypertrophy, in response to UCN is not yet documented. Cardiomyocytes from adult rats were stimulated for 48 h with UCN. Cell size, protein, and DNA contents were determined. Phosphorylated and total forms GSK-3β and the total amount of β-catenin were quantified by Western immunoblots. The effects of astressin, a UCN competitive receptor antagonist, were also evaluated. UCN increased cell size and the protein-to-DNA ratio, in accordance with a hypertrophic response. This effect was associated with increased phosphorylation of GSK-3β and marked accumulation of β-catenin, a downstream element to GSK-3β. All these effects were prevented by astressin and LY294002, an inhibitor of the phosphatidyl-inositol-3-kinase. UCN-induced cardiomyocytes hypertrophy is associated with regulation of GSK-3β, a pivotal kinase involved in cardiac hypertrophy, in a PI3K-dependent manner. Furthermore, the pharmacological blockade of UCN receptors was able to prevent UCN-induced hypertrophy, which leads to inhibition of the Akt/GSK-3β pathway.
    Heart and Vessels 04/2011; 27(2):202-7. DOI:10.1007/s00380-011-0141-5 · 2.07 Impact Factor
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    ABSTRACT: Introduction L’activation de la protéine kinase activée par l’AMP (AMPK) augmente la sensibilité à l’insuline et le transport de glucose dans le cœur. Il a été proposé que la voie de la p70S6K joue un rôle dans cet effet. La p70S6K est connue pour réduire la signalisation insulinique via un rétro-contrôle négatif impliquant la phosphorylation en sérine du substrat du récepteur insulinique IRS-1. Sachant que l’AMPK est capable d’inhiber la p70S6K, nous avons postulé que l’AMPK augmente la sensibilité à l’insuline en inhibant ce rétro-contrôle négatif. Matériels et méthodes Nous avons vérifié cette hypothèse dans des cardiomyocytes de rat en culture primaire soumis à différentes stimulations. Résultats La stimulation du transport de glucose par les biguanides (0.6 ± 0.1 vs contrôle: 0,1 ± 0,05 μmoles/mg.h, p ≤ 0,05) corrèle avec la phosphorylation de l’AMPK, tandis que celle induite par l’insuline (0,9 ± 0.1 μmoles/mg.h, p0,05) corrèle avec la phosphorylation d’Akt. Incubés ensemble, l’insuline et les biguanides induisent une surstimulation du transport de glucose (2,0 ± 0,2 μmoles/mg.h) et une surstimulation d’Akt qui corrèlent avec une inhibition de la p70S6K et une réduction de la phosphorylation en sérine d’IRS-1. Afin de vérifier le rôle de la p70S6K dans les effets insulino-sensibilisateurs des biguanides, nous avons utilisé la rapamycine, l’inhibiteur spécifique de la voie de la p70S6K. La rapamycine mime les effets des biguanides sur la phosphorylation insulino-dépendante de la p70S6K, d’IRS-1 et d’Akt. Par contre, elle est incapable d’amplifié les effets de l’insuline sur le transport de glucose (insuline+rapamycine: 1,1 ± 0,2 μmoles/mg.h). Conclusion L’effet insulino-sensibilisateur de l’AMPK sur la signalisation insulinique (incluant Akt) peut être expliqué par l’inhibition du rétro-contrôle négatif impliquant la p70S6K et IRS-1. A l’inverse, l’effet insulino-sensibilisateur de l’AMPK sur le transport de glucose est indépendant de ce mécanisme. En outre, nos résultats suggèrent que l’AMPK est une cible thérapeutique potentielle pour traiter l’insulino-résistance cardiaque.
    Diabetes & Metabolism 03/2011; 37(1). DOI:10.1016/S1262-3636(11)70548-1 · 3.27 Impact Factor
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    ABSTRACT: Like insulin, leucine stimulates the mammalian target of rapamycin (mTOR)/p70 ribosomal S6 kinase (p70(S6K)) axis in various organs. Insulin proceeds via the canonical association of phosphatidylinositol 3-kinase (PI3K), phosphoinositide-dependent protein kinase-1 (PDK1), and protein kinase B (PKB/Akt). The signaling involved in leucine effect, although known to implicate a PI3K mechanism independent of PKB/Akt, is more poorly understood. In this study, we investigated whether PDK1 could also participate in the events leading to mTOR/p70(S6K) activation in response to leucine in the heart. In wild-type hearts, both leucine and insulin increased p70(S6K) activity whereas, in contrast to insulin, leucine was unable to activate PKB/Akt. The changes in p70(S6K) activity induced by insulin and leucine correlated with changes in phosphorylation of Thr(389), the mTOR phosphorylation site on p70(S6K), and of Ser(2448) on mTOR, both related to mTOR activity. Leucine also triggered phosphorylation of the proline-rich Akt/PKB substrate of 40 kDa (PRAS40), a new pivotal mTOR regulator. In PDK1 knockout hearts, leucine, similarly to insulin, failed to induce the phosphorylation of mTOR and p70(S6K), leading to the absence of p70(S6K) activation. The loss of leucine effect in absence of PDK1 correlated with the lack of PRAS40 phosphorylation. Moreover, the introduction in PDK1 of the L155E mutation, which is known to preserve the insulin-induced and PKB/Akt-dependent phosphorylation of mTOR/p70(S6K), suppressed all leucine effects, including phosphorylation of mTOR, PRAS40, and p70(S6K). We conclude that the leucine-induced stimulation of the cardiac PRAS40/mTOR/p70(S6K) pathway requires PDK1 in a way that differs from that of insulin.
    AJP Endocrinology and Metabolism 04/2010; 298(4):E761-9. DOI:10.1152/ajpendo.00421.2009 · 3.79 Impact Factor

Publication Stats

337 Citations
88.95 Total Impact Points


  • 2006-2015
    • Catholic University of Louvain
      • • Institute of Experimental and Clinical Research (IREC)
      • • School of Medicine
      Лувен-ла-Нев, Walloon, Belgium
  • 2011
    • Cliniques Universitaires Saint-Luc
      Bruxelles, Brussels Capital Region, Belgium