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Acute systemic insulin intolerance does not alter the response of the Akt/GSK-3 pathway to environmental hypoxia in human skeletal muscle

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D'Hulst, Gommaar [KU Leuven] Sylow, Lykke Hespel, Peter Deldicque, Louise [UCL]

(eng) PURPOSE: To investigate how acute environmental hypoxia regulates blood glucose and downstream intramuscular insulin signaling after a meal in healthy humans. METHODS: Fifteen subjects were exposed for 4 h to normoxia (NOR) or to normobaric hypoxia (HYP, FiO2 = 0.11) in a randomized order 40 min after consumption of a high glycemic meal. A muscle biopsy from m. vastus lateralis and a blood sample were taken before (T0), after 1 h (T60) and 4 h (T240) in NOR or HYP and blood glucose levels were measured before exposure and every 30 min. RESULTS: In HYP, blood glucose was reduced 100 min (110.1 ± 5.4 in NOR vs 89.5 ± 4.7 mg dl(-1) in HYP) and 130 min (98.7 ± 3.8 in NOR vs 85.6 ± 4.9 mg dl(-1) in HYP) after completion of a meal, which resulted in an 83 % lower AUC in HYP compared to NOR (p = 0.006). This coincided with 40 % lower GLUT4 protein in the cytosolic fraction (p = 0.013) and a tendency to increase in the crude membrane fraction (p = 0.070) in HYP compared to NOR. At T240, blood glucose concentration was similar between HYP and NOR, whereas plasma insulin as well as phosphorylation of muscle Akt and GSK-3 was ~2-fold higher in HYP compared to NOR (p < 0.05). In contrast, Rac1 protein was less abundant in the membrane fraction in HYP compared to NOR (p = 0.003), reflecting lower activation. CONCLUSION: Acute environmental hypoxia initially reduced blood glucose response to a meal, possibly via an increase in GLUT4 abundance at the sarcolemmal membrane. Later on, whole body insulin intolerance developed independently of defects in conventional insulin signaling in skeletal muscle.

Document type Article de périodique (Journal article) – Article de recherche
Access type Accès interdit
Publication date 2015
Language Anglais
Journal information "European Journal of Applied Physiology" - Vol. 115, no. 6, p. 1219-1231 (2015)
Peer reviewed yes
Publisher Springer ((Germany) Berlin)
issn 1439-6319
e-issn 1439-6327
Publication status Publié
Affiliation UCL - SSS/IONS/CEMO-Pôle Cellulaire et moléculaire
Links
  1. Alvarez-Tejado Miguel, Naranjo-Suárez Salvador, Jiménez Concepción, Carrera Ana C., Landázuri Manuel O., del Peso Luis, Hypoxia Induces the Activation of the Phosphatidylinositol 3-Kinase/Akt Cell Survival Pathway in PC12 Cells : PROTECTIVE ROLE IN APOPTOSIS, 10.1074/jbc.m011688200
  2. BROZINICK Joseph T., REYNOLDS Thomas H., DEAN David, CARTEE Gregory, CUSHMAN Samuel W., 1-[N,O-Bis-(5-isoquinolinesulphonyl)-N-methyl-L-tyrosyl]-4-phenylpiperazine (KN-62), an inhibitor of calcium-dependent camodulin protein kinase II, inhibits both insulin- and hypoxia-stimulated glucose transport in skeletal muscle, 10.1042/0264-6021:3390533
  3. Bustelo Xosé R., Sauzeau Vincent, Berenjeno Inmaculada M., GTP-binding proteins of the Rho/Rac family: regulation, effectors and functions in vivo, 10.1002/bies.20558
  4. Cartee GD, Douen AG, Ramlal T, Klip A, Holloszy JO (1991) Stimulation of glucose transport in skeletal muscle by hypoxia. J Appl Physiol 70:1593–1600
  5. Castillo Oscar, Woolcott Orison O., Gonzales Elizabeth, Tello Victoria, Tello Lida, Villarreal Carmen, Méndez Nicolás, Damas Lucy, Florentini Edgar, Residents at High Altitude Show a Lower Glucose Profile Than Sea-Level Residents Throughout 12-Hour Blood Continuous Monitoring, 10.1089/ham.2007.8407
  6. Catalucci Daniele, Latronico Michael V. G., Ceci Marcello, Rusconi Francesca, Young Howard S., Gallo Paolo, Santonastasi Marco, Bellacosa Alfonso, Brown Joan Heller, Condorelli Gianluigi, Akt Increases Sarcoplasmic Reticulum Ca2+Cycling by Direct Phosphorylation of Phospholamban at Thr17, 10.1074/jbc.m109.036566
  7. Chiu Tim T., Jensen Thomas E., Sylow Lykke, Richter Erik A., Klip Amira, Rac1 signalling towards GLUT4/glucose uptake in skeletal muscle, 10.1016/j.cellsig.2011.05.022
  8. DeFronzo R. A., Jacot E., Jequier E., Maeder E., Wahren J., Felber J. P., The Effect of Insulin on the Disposal of Intravenous Glucose: Results from Indirect Calorimetry and Hepatic and Femoral Venous Catheterization, 10.2337/diab.30.12.1000
  9. D'Hulst G., Jamart C., Van Thienen R., Hespel P., Francaux M., Deldicque L., Effect of acute environmental hypoxia on protein metabolism in human skeletal muscle, 10.1111/apha.12086
  10. Dongiovanni Paola, Valenti Luca, Ludovica Fracanzani Anna, Gatti Stefano, Cairo Gaetano, Fargion Silvia, Iron Depletion by Deferoxamine Up-Regulates Glucose Uptake and Insulin Signaling in Hepatoma Cells and in Rat Liver, 10.2353/ajpath.2008.070097
  11. Du Jun, Xu Rui, Hu Zhenzhen, Tian Yinhui, Zhu Yichao, Gu Luo, Zhou Lei, PI3K and ERK-Induced Rac1 Activation Mediates Hypoxia-Induced HIF-1α Expression in MCF-7 Breast Cancer Cells, 10.1371/journal.pone.0025213
  12. Emerling Brooke M., Weinberg Frank, Snyder Colleen, Burgess Zach, Mutlu Gökhan M., Viollet Benoit, Budinger G.R. Scott, Chandel Navdeep S., Hypoxic activation of AMPK is dependent on mitochondrial ROS but independent of an increase in AMP/ATP ratio, 10.1016/j.freeradbiomed.2009.02.019
  13. Favier F. B., Costes F., Defour A., Bonnefoy R., Lefai E., Bauge S., Peinnequin A., Benoit H., Freyssenet D., Downregulation of Akt/mammalian target of rapamycin pathway in skeletal muscle is associated with increased REDD1 expression in response to chronic hypoxia, 10.1152/ajpregu.00550.2009
  14. Freckmann Guido, Baumstark Annette, Jendrike Nina, Zschornack Eva, Kocher Serge, Tshiananga Jacques, Heister Frank, Haug Cornelia, System Accuracy Evaluation of 27 Blood Glucose Monitoring Systems According to DIN EN ISO 15197, 10.1089/dia.2009.0128
  15. Gamboa J. L., Garcia-Cazarin M. L., Andrade F. H., Chronic hypoxia increases insulin-stimulated glucose uptake in mouse soleus muscle, 10.1152/ajpregu.00078.2010
  16. Gkourogianni Alexandra, Kosteria Ioanna, Telonis Aristeidis G., Margeli Alexandra, Mantzou Emilia, Konsta Maria, Loutradis Dimitrios, Mastorakos George, Papassotiriou Ioannis, Klapa Maria I., Kanaka-Gantenbein Christina, Chrousos George P., Plasma Metabolomic Profiling Suggests Early Indications for Predisposition to Latent Insulin Resistance in Children Conceived by ICSI, 10.1371/journal.pone.0094001
  17. GUALANO BRUNO, DE SALLES PAINNELI VITOR, ROSCHEL HAMILTON, ARTIOLI GUILHERME GIANNINI, NEVES MANOEL, DE SÁ PINTO ANA LÚCIA, DA SILVA MARIA ELIZABETH ROSSI, CUNHA MARIA ROSÁRIA, OTADUY MARIA CONCEPCIÓN GARCÍA, DA COSTA LEITE CLAUDIA, FERREIRA JÚLIO CÉSAR, PEREIRA ROSA MARIA, BRUM PATRÍCIA CHAKUR, BONFÁ ELOISA, LANCHA ANTONIO HERBERT, Creatine in Type 2 Diabetes : A Randomized, Double-Blind, Placebo-Controlled Trial, 10.1249/mss.0b013e3181fcee7d
  18. Hayashi T., Hirshman M. F., Fujii N., Habinowski S. A., Witters L. A., Goodyear L. J., Metabolic stress and altered glucose transport: activation of AMP-activated protein kinase as a unifying coupling mechanism, 10.2337/diabetes.49.4.527
  19. Kelly Karen R., Williamson David L., Fealy Ciarán E., Kriz David A., Krishnan Raj K., Huang Hazel, Ahn Janice, Loomis Joseph L., Kirwan John P., Acute altitude-induced hypoxia suppresses plasma glucose and leptin in healthy humans, 10.1016/j.metabol.2009.07.014
  20. Larsen Jens Jørn, Hansen Jesper Melchior, Olsen Niels Vidiendal, Galbo Henrik, Dela Flemming, The effect of altitude hypoxia on glucose homeostasis in men, 10.1111/j.1469-7793.1997.241bf.x
  21. Lecoultre V., Peterson C. M., Covington J. D., Ebenezer P. J., Frost E. A., Schwarz J.-M., Ravussin E., Ten Nights of Moderate Hypoxia Improves Insulin Sensitivity in Obese Humans, 10.2337/dc13-1350
  22. Marquez Juan L, Rubinstein Scott, Fattor Jill A., Shah Omer, Hoffman Andrew R., Friedlander Anne L., Cyclic Hypobaric Hypoxia Improves Markers of Glucose Metabolism in Middle-Aged Men, 10.1089/ham.2012.1057
  23. Masschelein E., Van Thienen R., D'Hulst G., Hespel P., Thomis M., Deldicque L., Acute environmental hypoxia induces LC3 lipidation in a genotype-dependent manner, 10.1096/fj.13-239863
  24. Mattagajasingh Subhendra N., Yang Xiao Ping, Irani Kaikobad, Mattagajasingh Ilwola, Becker Lewis C., Activation of Stat3 in endothelial cells following hypoxia–reoxygenation is mediated by Rac1 and protein kinase C, 10.1016/j.bbamcr.2012.02.008
  25. Mollen Kevin P., McCloskey Carol A., Tanaka Hiroyuki, Prince Jose M., Levy Ryan M., Zuckerbraun Brian S., Billiar Timothy R., HYPOXIA ACTIVATES c-JUN N-TERMINAL KINASE VIA RAC1-DEPENDENT REACTIVE OXYGEN SPECIES PRODUCTION IN HEPATOCYTES : , 10.1097/shk.0b013e3180485acd
  26. Mu James, Brozinick Joseph T, Valladares Otto, Bucan Maja, Birnbaum Morris J, A Role for AMP-Activated Protein Kinase in Contraction- and Hypoxia-Regulated Glucose Transport in Skeletal Muscle, 10.1016/s1097-2765(01)00251-9
  27. Nielsen Jakob N., Wojtaszewski Jørgen F. P., Regulation of glycogen synthase activity and phosphorylation by exercise, 10.1079/pns2004348
  28. Oltmanns Kerstin M., Gehring Hartmut, Rudolf Sebastian, Schultes Bernd, Rook Stefanie, Schweiger Ulrich, Born Jan, Fehm Horst L., Peters Achim, Hypoxia Causes Glucose Intolerance in Humans, 10.1164/rccm.200308-1200oc
  29. Osei K., Falko J. M., O'Dorisio T. M., Adam D. R., Decreased Serum C-Peptide/Insulin Molar Ratios After Oral Glucose Ingestion in Hyperthyroid Patients, 10.2337/diacare.7.5.471
  30. Östman E, Granfeldt Y, Persson L, Björck I, Vinegar supplementation lowers glucose and insulin responses and increases satiety after a bread meal in healthy subjects, 10.1038/sj.ejcn.1602197
  31. Peltonen Garrett L., Scalzo Rebecca L., Schweder Melani M., Larson Dennis G., Luckasen Gary J., Irwin David, Hamilton Karyn L., Schroeder Thies, Bell Christopher, Sympathetic inhibition attenuates hypoxia induced insulin resistance in healthy adult humans : Sympathetic inhibition attenuates hypoxia-induced insulin resistance, 10.1113/jphysiol.2011.227090
  32. Radu Maria, Semenova Galina, Kosoff Rachelle, Chernoff Jonathan, PAK signalling during the development and progression of cancer, 10.1038/nrc3645
  33. Reaven GM (1979) Effects of differences in amount and kind of dietary carbohydrate on plasma glucose and insulin responses in man. Am J Clin Nutr 32:2568–2578
  34. Regazzetti C., Peraldi P., Gremeaux T., Najem-Lendom R., Ben-Sahra I., Cormont M., Bost F., Le Marchand-Brustel Y., Tanti J.-F., Giorgetti-Peraldi S., Hypoxia Decreases Insulin Signaling Pathways in Adipocytes, 10.2337/db08-0457
  35. Richter E. A., Hargreaves M., Exercise, GLUT4, and Skeletal Muscle Glucose Uptake, 10.1152/physrev.00038.2012
  36. Roberts AC, Reeves JT, Butterfield GE, Mazzeo RS, Sutton JR, Wolfel EE, Brooks GA (1996) Altitude and beta-blockade augment glucose utilization during submaximal exercise. J Appl Physiol 80(2):605–615
  37. Sakagami H., Makino Y., Mizumoto K., Isoe T., Takeda Y., Watanabe J., Fujita Y., Takiyama Y., Abiko A., Haneda M., Loss of HIF-1  impairs GLUT4 translocation and glucose uptake by the skeletal muscle cells, 10.1152/ajpendo.00597.2012
  38. Sandström Marie E., Zhang Shi-Jin, Bruton Joseph, Silva José P., Reid Michael B., Westerblad Håkan, Katz Abram, Role of reactive oxygen species in contraction-mediated glucose transport in mouse skeletal muscle : Reactive oxygen species and glucose transport during contraction, 10.1113/jphysiol.2006.110601
  39. Satoh Takaya, Rho GTPases in insulin-stimulated glucose uptake, 10.4161/sgtp.28102
  40. Sigal R. J., Kenny G. P., Wasserman D. H., Castaneda-Sceppa C., White R. D., Physical Activity/Exercise and Type 2 Diabetes: A consensus statement from the American Diabetes Association, 10.2337/dc06-9910
  41. Singh Bhawna, Surrogate markers of insulin resistance: A review, 10.4239/wjd.v1.i2.36
  42. Sylow L., Jensen T. E., Kleinert M., Mouatt J. R., Maarbjerg S. J., Jeppesen J., Prats C., Chiu T. T., Boguslavsky S., Klip A., Schjerling P., Richter E. A., Rac1 Is a Novel Regulator of Contraction-Stimulated Glucose Uptake in Skeletal Muscle, 10.2337/db12-0491
  43. Sylow L., Jensen T. E., Kleinert M., Hojlund K., Kiens B., Wojtaszewski J., Prats C., Schjerling P., Richter E. A., Rac1 Signaling Is Required for Insulin-Stimulated Glucose Uptake and Is Dysregulated in Insulin-Resistant Murine and Human Skeletal Muscle, 10.2337/db12-1148
  44. Sylow Lykke, Kleinert Maximilian, Pehmøller Christian, Prats Clara, Chiu Tim T., Klip Amira, Richter Erik A., Jensen Thomas E., Akt and Rac1 signaling are jointly required for insulin-stimulated glucose uptake in skeletal muscle and downregulated in insulin resistance, 10.1016/j.cellsig.2013.11.007
  45. Taniguchi Cullen M, Finger Elizabeth C, Krieg Adam J, Wu Colleen, Diep Anh N, LaGory Edward L, Wei Kevin, McGinnis Lisa M, Yuan Jenny, Kuo Calvin J, Giaccia Amato J, Cross-talk between hypoxia and insulin signaling through Phd3 regulates hepatic glucose and lipid metabolism and ameliorates diabetes, 10.1038/nm.3294
  46. Treebak Jonas T., Pehmøller Christian, Kristensen Jonas M., Kjøbsted Rasmus, Birk Jesper B., Schjerling Peter, Richter Erik A., Goodyear Laurie J., Wojtaszewski Jørgen F. P., Acute exercise and physiological insulin induce distinct phosphorylation signatures on TBC1D1 and TBC1D4 proteins in human skeletal muscle : Phosphorylation signatures of TBC1D1 and TBC1D4 in skeletal muscle, 10.1113/jphysiol.2013.266338
  47. Van Thienen R., D'Hulst G., Deldicque L., Hespel P., Biochemical artifacts in experiments involving repeated biopsies in the same muscle, 10.14814/phy2.286
  48. Vittone Leticia, Phospholamban phosphorylation by CaMKII under pathophysiological conditions, 10.2741/3131
  49. Wojtaszewski Jørgen F.P, Laustsen Jan L, Derave Wim, Richter Erik A, Hypoxia and contractions do not utilize the same signaling mechanism in stimulating skeletal muscle glucose transport, 10.1016/s0304-4165(98)00011-7
  50. Wolever TM, Bolognesi C (1996) Prediction of glucose and insulin responses of normal subjects after consuming mixed meals varying in energy, protein, fat, carbohydrate and glycemic index. J Nutr 126:2807–2812
  51. Wright D. C., Contraction- and hypoxia-stimulated glucose transport is mediated by a Ca2+-dependent mechanism in slow-twitch rat soleus muscle, 10.1152/ajpendo.00561.2004
Bibliographic reference D'Hulst, Gommaar ; Sylow, Lykke ; Hespel, Peter ; Deldicque, Louise. Acute systemic insulin intolerance does not alter the response of the Akt/GSK-3 pathway to environmental hypoxia in human skeletal muscle. In: European Journal of Applied Physiology, Vol. 115, no. 6, p. 1219-1231 (2015)
Permanent URL http://hdl.handle.net/2078.1/160954