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2. 35th Annual Meeting of the European Association for the Study of Diabetes
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Melander, A., Olsson, J., Lindberg, G., Salzman, A., Howard, T., Stang, P., Lydick, E., Emslie-Smith, A., Boyle, D. I. R., Evans, J. M. M., Macdonald, T. M., Bain, J., Sullivan, F., Juhl, C., Pørksen, N., Sturis, J., Hollingdal, M., Pincus, S., Veldhuis, J., Dejgaard, A., Schmitz, O., Kristensen, J. S., Frandsen, K. B., Bayer, Th., Müller, P., Dunning, B. E., Paladini, S., Gutierrez, C., Deacon, R., Valentin, M., Grunberger, G., Weston, W. M., Patwardhan, R., Rappaport, E. B., Sargeant, L. A., Wareham, N. J., Khaw, K. T., Zethelius, Björn, Lithell, Hans, Hales, C. Nicholas, Berne, Christian, Lakka, H.-M., Oksanen, L., Tuomainen, T.-P., Kontula, K., Salonen, J. T., Dekker, J. M., de Boks, P., de Vegt, F., Stehouwer, C. D. A., Nijpels, G., Bouter, L. M., Heine, R. J., Bruno, G., Cavallo-Perin, P., Bargero, G., D’Errico, N., Borra, M., Macchia, G., Pagano, G., Newton, R. W., Ruta, D. A., New, J. P., Wallace, C., Roxburgh, M. A., Young, R. J., Vaughan, N. J. A., Elliott, P., Brennan, G., Devers, M., MacAlpine, R., Steinke, D., Lawson, D. H., Decallonne, B., Casteels, K., Gysemans, C., Bouillon, R., Mathieu, C., Linn, Thomas, Strate, Christine, Schneider, Kerstin, Funda, D. P., Jirsa, M., Kozáková, H., Kaas, A., Kofronová, O., Tlaskalová-Hogenová, H., Buschard, K., Wanka, H., Hartmann, A., Kuttler, B., Rasmussen, S. B., Sørensen, T. S., Markholst, H., Petersen, J. S., Karounos, D., Dyrberg, T., Mabley, J. G., Haskó, G., Szabó, C., Seissler, J., Nguyen, T. B. T., Steinbrenner, H., Scherbaum, W. A., Cipriani, R., Gabriele, A., Sensi, M., Guidobaldi, L., Pantellini, F., Cerrito, M. G., Scarpa, S., Di Mario, U., Morano, S., Ceolotto, G., Iori, E., Baritono, E., Del Prato, S., Semplicini, A., Trevisan, R., Zerbini, G., Meregalli, G., Asnaghi, V., Tentori, F., Maestroni, A., Mangili, R., Marescotti, C., Vedovato, M., Tiengo, A., Tadjieva, J., Mankovsky, B. N., Van Aken, S., Raes, A., Vande Walle, J., Matthys, D., Craen, M., Hansen, H. P., Lund, S. S., Rossing, P., Jensen, T., Parving, H.-H., Andersen, S., Tarnow, L., Hansen, B. V., Trautner, C., Haastert, B., Ennenbach, N., Willich, S., Tabák, Á. Gy., Orchard, T. J., Spranger, J., Preissner, K. T., Schatz, H., Pfeiffer, A., Cantón, A., Burgos, R., Hernández, C., Lecube, A., Mesa, J., Segura, R. M., Mateo, C., Simó, R., Fathallah, L., Greene, D. A., Obrosova, I., Gilbert, R. E., Kelly, D. J., Cox, A. J., Berka-Wilkinson, J. L., Taylor, H. R., Panagiotopoulos, S., Lee, V., Jerums, G., Cooper, M. E., Hitman, G. A., Aganna, E., Ogunkolade, W. B., Rema, M., Deepa, R., Shanthi-Rani, C. S., Barakat, K., Kumarajeewa, T. R., Cassell, P. G., McDermott, M. F., Mohan, V., Ways, K., Bursell, S., Devries, T., Woodworth, J., Alatorre, C., King, G., Aiello, L. P., Karisen, A. E., Pavlovic, D., Nielsen, K., Jensen, J., Andersen, H. U., Pociot, F., Mandrup-Poulsen, T., Eizirik, D. L., Nerup, J., Lortz, S., Tiedge, M., Lenzen, S., Lally, F. J., Bone, A. J., Darville, M. I., Ho, Y.-S., Sternesjö, J., Sandler, S., Chen, M.-C., Schuit, F., Pipeleers, D. G., Merezak, S., Hardikar, A., Hoet, J. J., Remacle, C., Reusens, B., Bréant, B., Garofano, A., Czernichow, P., Kubota, N., Terauchi, Y., Miki, H., Tamemoto, H., Yamauchi, T., Nakano, R., Komeda, K., Eto, K., Tobe, K., Kimura, S., Kadowaki, T., Ide, T., Murakami, K., Tsunoda, M., Mochizuki, T., Ozanne, S. E., Nave, B. T., Wang, C. L., Dorling, M. W., Petry, C. J., Koopmans, S. J., van der Bent, C., Que, I., Radder, J. K., Sebokova, E., Sana, A. K., Klimes, I., Ruderman, N., Morviducci, L., Pastore, L., Morelli, S., Sagratella, E., Zorretta, D., Buongiomo, A., Tamburrano, G., Giaccari, A., Martinenghi, Sabina, De Angelis, Gabriella Cusella, Ravasi, Flavio, Bifari, Francesco, Bordignon, Claudio, Falqui, Luca, Kessler, A., Dransfeld, O., Sasson, S., Tomas, E., Zorzano, A., Eckel, J., Thorsby, P., Rosenfalck, A. M., Kjems, L., Hanssen, K. F., Madsbad, S., Birkeland, K. I., Hamilton-Wessler, M., Markussen, J., Bergman, R. N., Melki, V., Hanaire-Broutin, H., Bessières-Lacombe, S., Tauber, J.-P., Home, P. D., Lindholm, A., Riis, A., Rosenstock, J., Schwartz, S., Clark, C., Edwards, M., Donley, D., Swift, P., Mortensen, H. B., Lynggaard, H., Hougaard, P., Cull, C. A., Neil, H. A. W., Frighi, V., Manley, S. E., Holman, R. R., Turner, R. C., Steiner, G., Davis, W. A., Weeraratna, T., Bruce, D. G., Davis, T. M. E., Vergès, B., Duvillard, L., Pont, F., Florentin, E., Gambert, Ph., Benko, B., Ljubić, S., Turk, Z., Granić, M., März, W., Wollschläger, H., Klein, G., Neiss, A., Wehling, M., Huxtable, S. J., Saker, P. J., Walker, M., Frayling, T. M., Levy, J. C., O’Rahilly, S., Hattersley, A. T., McCarthy, M. I., Orecchio, A., Giacchini, A., Dominici, R., Canettieri, G., Trinti, B., Zani, M., Andreoli, M., Sciacchitano, S., de Silva, A. M., Whitecross, K., Pasco, J., Kotowicz, M., Nicholson, G., Zimmet, P., Boyko, E. J., Collier, G. R., Frittitta, L., Pizzuti, A., Argiolas, A., Graci, S., Goldfine, I. D., Bozzali, M., Ercolino, T., Costanzo, B., Iacoviello, L., Tassi, V., Trischitta, V., Wauters, M., Rankinen, T., Mertens, I., Chagnon, M., Bouchard, C., Van Gaal, L., Sivenius, K., Valve, R., Hakkarainen, V., Niskanen, L., Laakso, M., Uusitupa, M., Beridze, N., Japaridze, M., Kurashvili, R., Dundua, M., Kebuladze, G., Kazakhashvili, N., Offley-Shore, B., Thomas, B., Ghebremeskel, K., Crawford, M., Lowy, C., Eriksson, Ulf J., Martin Simán, C., Wisse, Bert, Gittenberger-de Groot, Adriana C., Wentzel, P., Eriksson, U. J., Wender-Ożegowska, E., Drews, K., Biczysko, R., Bronisz, A., Rość, D., Graczykowska-Koczorowska, A., Kotschy, M., Sokup, A., Kohnert, K. D., Besch, W., Strese, J., Frick, U., Zander, E., Kemer, W., Škrha, J., Kvasnička, J., Kalvodová, B., Hilgertová, J., Schatteman, K., Goossens, F., Scharpé, S., De Leeuw, I., Hendriks, D., Legakis, I. N., Panayiotou, D., Mountokalakis, Th. D., Enderle, M. D., Beckmann, P., Balletshofer, B., Rittig, K., Maerker, E., Volk, A., Meisner, C., Jacob, S., Matthaei, S., Häring, H. U., Rett, K., Ueda, K., Nakagawa, T., Shimajiri, Y., Kokawa, M., Matsumoto, E., Sasaki, H., Sanke, T., Nanjo, K., McKinnon, Caroline M., Macfarlane, Wendy M., Docherty, Kevin, Furukawa, N., Shirotani, T., Kishikawa, H., Kaneko, K., Araki, E., Shichiri, M., Prentki, M., Roduit, R., Susini, S., Buteau, J., Ejrnæs, A. M., Andersen, N. Aa., Osterhoff, M., Möhlig, M., Ortmann, J., Bikashaghi, F., Mayer, C., Bikashagi, F., Ackermans, M. T., Pereira Arias, A. M., Bisschop, P. H. L. T., Endert, E., Sauerwein, H. P., Romijn, J. A., Gastaldelli, A., Baldi, S., Pettiti, M., Natali, A., Frascerra, S., Camastra, S., Toschi, E., Ferrannini, E., Stingl, H., Krssak, M., Bischof, M. G., Krebs, M., Fürnsinn, C., Nowotny, P., Waldhäusl, W., Roden, M., Neeft, M., Meijer, A. J., Båvenholm, P., Pigon, J., Efendic, S., Kästenbauer, T., Sauseng, S., Sokol, G., Auinger, M., Irsigler, K., Abbott, C. A., Carrington, A. L., Faragher, B., Kulkarni, J., Van Ross, E. R. E., Boulton, A. J. M., Armstrong, D. G., Hadi, S., Nguyen, H. C., Harkless, L. B., Jirkovská, A., Kasalicky, P., Hosová, J., Skibova, J., Uccioli, L., Caselli, A., Giacomozzi, C., Macellari, V., Giurato, L., Lardieri, L., Menzinger, G., Pham, H. T., Rosenblum, B. I., Lyons, T. E., Giurini, J. M., Smakowski, P., Chrzan, J. S., Habershaw, G. M., Veves, A., Foster, A. M., Bates, M., Doxford, M., Edmonds, M. E., Kecha, O., Winkler, R., Martens, H., Collette, J., Lefèbvre, P. J., Greiner, D., Geenen, V., Atlan-Gepner, C., Naspetti, M., Valéro, R., Barad, M., Lepault, F., Vialettes, B., Naquet, P., de Galan, B., Netea, M. G., Hancu, N., Smits, P., Van der Meer, J. W. M., Osterbye, T., Jørgensen, K. H., Tranum-Jensen, J., Fredman, P., Høy, M., Bokvist, K., Olsen, H. L., Horn, T., Gromada, J., Laub, R., Lohmann, T., Hahn, H. J., Adler, T., Emmrich, F., Rabuazzo, A. M., Lupi, R., Dotta, F., Patanè, G., Marselli, L., Realacci, M., Piro, S., Del Guerra, S., Santangelo, C., Navalesi, R., Purrello, F., Marchetti, P., de Vos, P., Visser, L., de Haan, B. J., Klok, P., van Schilfgaarde, R., Poppema, S., Juang, J.-H., Kuo, C.-H., Hsu, B. R.-S., Nacher, V., Pérez, M., Biarnés, M., Raurell, M., Soler, J., Montanya, E., Ritzel, R., Maubach, J., Büsing, M., Becker, T., Klempnauer, J., Hücking, K., Schmiegel, W. H., Nauck, M. A., Bouček, P., Saudek, F., Adamec, M., Kožitarová, R., Jedináková, T., Vlasáková, Z., Skibová, J., Bartoš, V., Maffi, P., Bertuzzi, F., Aldrighetti, L., Taglietti, M. V., Castelnuovo, A., Pozza, G., Di Carlo, V., Secchi, A., Renier, G., Mamputu, J.-C., Gillespie, J. S., McMaster, D., Mercer, C., Trimble, E. R., Lecomte, M., Véricel, E., Paget, C., Ruggiero, D., Lagarde, M., Wiernsperger, N., Pricci, F., Leto, G., Amadio, L., Cordone, S., Iacobini, C., Catalano, S., Violi, F., Rotella, C. M., Pugliese, G., Zicari, A., Gradini, R., Sale, P., Pala, L., Cresci, B., Giannini, S., Manuelli, C., Dahlfors, G., Arnqvist, H. J., Gonelle-Gispert, C., Halnan, P. A., Sadoul, K., Wolter, S., Lang, J., Niwa, T., Yu, W., Hidaka, H., Senda, T., Niki, I., Fukasawa, T., Renstrom, E., Barg, S., Seward, E., Rorsman, P., Rutter, G. A., Molinete, M., Lilla, V., Ravazzola, M., Halban, P. A., Efanov, A. M., Bertorello, A. M., Zaitsev, S. V., Zwiller, J., Berggren, P.-O., MŞengül, A., Salman, F., Sargrn, M., Özer, E., Karşidaǧ, K., Salman, S., Gedik, S., Satman, İ., Dinççaǧ, N., Yılmaz, M. T., Lloyd, A., Hopkinson, P. K., Testa, M. A., Blonde, L., Turner, R. R., Hayes, J., Simonson, D. C., van der Ven, N. C. W., Lubach, C. H. C., Snoek, F. J., Mollema, E. D., van der Ploeg, H. M., Danne, T., Hoey, H., McGee, H., Fitzgerald, H., Lernmark, B., Thernlund, G., Fredin, K., Hägglöf, B., Lugari, R., Dell’Anna, C., Ugolotti, D., Dei Cas, A., Barilli, A. L., Sard, L., Marani, B., Iotti, M., Zandomeneghi, R., Gnudi, A., Kjems, L. L., Volund, Aa., Toft-Nielsen, M., Damholt, M. B., Hilsted, L., Hughes, T. E., Krarup, T., Holst, J. J., Young, A., Gottlieb, A., Fineman, M., Kolterman, O., Cancelas, J., García-Martínez, J. A., Villanueva-Peñacarrillo, M. L., Valverde, I., Malaisse, W. J., Filipsson, K., Ahrén, B., Balkan, B., Kwasnik, L., Battle, B., Li, X., Egan, J. M., Clocquet, A. R., Elahi, D., Petrella, E., Pricket, K., Petersen, K. F., Sullivan, J. T., Amatruda, J. M., Livingston, J. N., Shulman, G. I., Freyse, E.-J., Knospe, S., Glund, K., Demuth, H.-U., Walker, D., Malik, R. A., Reljanovic, M., Barada, A., Milicevic, Z., Tack, Cees J., Goldstein, David S., Van Huysen, C., Stevens, M. J., Cao, X., Sundkvist, G., Dahlin, L.-B., Eriksson, K.-F., Rosén, I., Lattimer, S. A., Sima, A. A. F., Sullivan, K., Shaw, J. E., de Courten, M. P., Zimmet, P. Z., Gourdy, P., Ruidavets, J. B., Arveiler, D., Amouyel, Ph., Bingham, A., Tauber, J. P., Lam, K. S. L., Wat, N. M. S., Lam, T. H., Janus, E. D., de Pablos, P., Rodriguez, F., Martínez, J., Sánchez, V., Santana, C., García, I., Macías, A., Levin, K., Hother-Nielsen, O., Henriksen, J. E., Beck-Nielsen, H., Brechtel, K., Machann, J., Koch, M., Nielsen, M., Löblein, K., Becker, R., Denignger, M., Renn, W., Machicao, F., Claussen, C. D., Schick, F., Diraison, F., Moulin, P., Beylot, M., Thams, P., Capito, K., Eliasson, Lena, Barg, Sebastian, Göpel, Sven, Kanno, Takahiro, Renström, Erik, Meda, P., Charollais, A., Gjnovci, A., Calabrese, A., Wonkam, A., Caton, D., Wisznievski, L., Serre, V., Cogne, F., Bauquis, J., Bosco, D., Huarte, J., Herrera, P., Gotfredsen, C. F., Vessby, B., Manuel y Keenoy, B., Engelen, W., Vertommen, J., Schrans, S., Louheranta, A., Lindström, J., Tuomilehto, J., Segal, K. R., Heymsfield, S., Hauptman, J., Boldrin, M., Lucas, C., Pandolfi, A., Cetrullo, D., Polishchuck, R., Alberta, M., Pellegrini, G., Calafiore, A., Vitacolonna, E., Capani, F., Consoli, A., Halleux, C. M., Gillot, E. F., Brichard, S. M., Van der Planken, M., Corthouts, B., Peiffer, F., Scholten, D., Walke, M., Assert, R., Pirags, V., Pedula, K. L., Hillier, T. A., Brown, J. B., Santini, S. A., Marra, G., Cotroneo, P., Manto, A., Di Leo, M. A. S., Di Gregorio, S., Tordi, A., Pitocco, D., Ruotolo, V., Ghirlanda, G., Temelkova-Kurktschiev, T., Schaper, F., Koehler, C., Henkel, E., Hanefeld, M., Mancini, L., Citterio, F., Cotroneo, A., Ceroone, S., Castagneto, M., Rajbhandari, S. M., Dent, M. T., Plater, M. E., Harris, N. D., Tesfaye, S., Ward, J. D., Dupuy, O., Mayaudon, H., Lecoules, S., Bauduceau, B., Palou, M., Farret, O., Molinié, C., Antonelli-Incalzi, R., Fuso, L., Giordano, A., Calcagni, M. L., Todaro, L., Basso, S., Tramaglino, L. M., Troncone, L., Pistelli, R., Guillot, R., Bringuier, A., Porokhov, B., Guillausseau, P. J., Feldmann, G., Zivanic, S., Cizmic, M., Dragojevic, R., Vanovic, M., Borghouts, L. B., van Kranenburg, G. P. J., Schaart, G., Keizer, H. A., Niess, A. M., Dickuth, H. H., Lutz, O., Barbe, P., Calazel-Fournier, C., Hernandez, G., Saint-Martin, F., Galitzky, J., Gonçalves, A. A., da Silva, E. C., Brito, I. J. L., da Silva, C. A., Lawrence, N. J., Kousta, E., Mulnier, H., Penny, A., Millauer, B., Johnston, D. G., Robinson, S., Perriello, G., Pimenta, W., Pampanelli, S., Lucidi, P., Lepore, M., Porcellati, F., Cordoni, M. C., De Feo, P., Bolli, G. B., Sjöstrand, M., Holmäng, A., Lönnroth, P., Hauer, B., Grauer, P., Artzner, S., Lang, R., Stumvoll, M., Monti, L. D., Piatti, P. M., Gemone, F., Valsecchi, G., Magni, M., Barbieri, E., Setola, E., Sandoli, E. P., Galli-Kienle, M., Pontiroli, A. E., Nichols, Gregory A., Brown, Jonathan B., Salzsieder, E., Boltz, H., Ramirez, J. C., Rutscher, A., Fischer, U., Koenig, Ch., Friske, M., Schramm, W., Landgraf, R., Bachmann, W., Bangemann, M., Groeneveld, G., Edvell, Anders, Lindström, Per, Tsiotra, P., Koukourava, A., Raptis, S. A., Tsigos, C., Boutou, E., Triandaffilopoulou, A., Egido, E. M., Rodríguez-Gallardo, J., Gutiérrez, E., García, P., Silvestre, R. A., Marco, J., Khan, Akhtar, Ling, Zong-Chao, Ahren, Bo, Efendic, Suad, Bünting, C., Du, X., Zhi Sui, G., Rösen, P., Koschinsky, T., Kearney, T. M., Sharp, P. S., Lapolla, A., Fedele, D., Martano, L., Garbeglio, M., Seraglia, R., Favretto, D., Traldi, P., Meerwaldt, R., Smit, A. J., Links, Th. P., v. Roon, A. M., Graaf, R., Gans, R. O. B., Deynelİ, O., Ersöz, H. Ö., Gogas, D., Fak, A. S., Akalin, S., Veglio, M., Sivieri, R., Chinaglia, A., Scaglione, L., Le, T., Wong, N., Detrano, R., Charles, M. A., Colhoun, H. M., Francis, D. P., Rubens, M., Underwood, S. R., Fuller, J. H., Knudsen, E., Sato, A., Nielsen, F. S., Bonora, E., Kiechl, S., Willeit, J., Oberhollenzer, F., Egger, G., Bonadonna, R., Muggeo, M., Festa, A., D’Agostino, R., Howard, G., Mykkänen, L., Tracy, R. P., Haffner, S. M., Poulsen, P., Vach, K., Ijzerman, R. G., Bakker, S. J. L., Truster, J., Crowther, N. J., Cameron, N., Gray, I. P., Chaillous, L., Carel, J. C., Thivolet, C., Boitard, C., Charbonnel, B., Saï, P., Decochez, K., Keymeulen, B., Somers, G., Dorchy, H., Rottiers, R., Winnock, F., ver Elst, K., Weets, I., Pipeleers, D., Gorus, F., Seebaum, S., Schumm-Draeger, P.-M., Petzoldt, R., Federlin, K., Bonnevie-Nielsen, V., Martensen, P. M., Justesen, J., Worsaa, A., Karlsson, Maria, Sederholm, Sofia, Ludvigsson, Johnny, Bélicar, P., Dale, C., Vague, Ph., Alessis, C., Lassmann-Vague, V., Bode, B. W., Gross, T. M., Ghegan, M., Steed, R. D., Davidson, P. C., Ordoñez, A., Rubio, J. L., Sulleiro, J. M., Buendía, J. P., Zamora, J., Castillo, M., Schaupp, L., Ellmerer, M., Brunner, G. A., Sendlhofer, G., Schlack, Ch., Skrabal, F., Wach, P., Pieber, T. R., Heinemann, L., Krämer, U., Klötzer, H. M., Hermann, M., Cosgrove, K. E., Chapman, J. C., Shepherd, R. M., McIntyre, S., Butler, P. C., Dunne, M. J., Brekardin, E., Dörschner, H., Schwanstecher, C., Schwanstecher, M., Uhde, I., Emmanouilidou, E., Teschemacher, A. G., Pouli, A. E., Gylfe, E., Tengholm, A., Hellman, B., Perfetti, R., Aggarwal, S., Müller, Günter, Welte, Stefan, Wied, Susanne, Valverde, A. M., Mur, C., Kahn, C. R., Benito, M., Rondinone, C. M., Peterson, T., Laviola, L., Belsanti, G., Logoluso, F., Napoli, R., Davalli, A. M., Weir, G. C., Giorgino, R., Giorgino, F., Flesch, S., Hompesch, B., Rave, K., Susanto, F., Kühn-Velten, W. N., Heise, T., Rendell, M., Dole, J., Esper, R. J., Stein, E., Lemme, L., Rubinstein, A., Maritz, F. J., Soule, S., Market, A., Chajek-Shaul, T., Maislos, M., Tal, S., Stolero, D., Josefsen, K., Beckmann, H., Petersen, C., Ekman, R., Efanova, I., Zaitsev, S., Berggren, P. O., Birkenbach, M., Holl, R. W., Rosenbauer, J., Grabert, M., Icks, A., Schwab, O., Reile, K., Janssen, M. M. J., de Jongh, R. T., Casteleijn, S., Masurel, N., Hoogma, R. P. L. M., Santeusanio, F., Brunetti, P., Fanelli, C. G., Laureti, S., Bartocci, L., Maran, A., Crepaldi, C., Trupiani, S., Macdonald, I. A., Avogaro, A., Bouman, S. D., Keitz, M., Bruggink, J. E., Scheurink, A. J. W., Strubbe, J. H., Steffens, A. B., Ferguson, S. C., McCrimmon, R. J., Perros, P., Best, J. J. K., Deary, I. J., Frier, B. M., Robinson, R. T. C. E., Ireland, N. H., Bedford, C., Fairclough, E., Hudson, S., Heller, S. R., Borch-Johnsen, K., Berger, M., Overmann, H., Bender, R., Blank, M., Sawicki, P., Jörgens, V., Mühlhauser, I., Nosadini, R., Sailer, A., Dalla Vestra, M., Brocco, E., Piarulli, F., Frigato, F., Sambataro, M., Velussi, M., Baggio, B., Fioretto, P., Jager, A., van Hinsbergh, V. W. M., Kostense, P. J., Nrjpels, G., Gæde, P., Pedersen, O., Andrysiak-Mamos, E., Majkowska, L., Krzyżanowska, B., Pilarska, K., Czekalski, S., Mazzon, C., Brocco, S., Field, L. L., Nejentsev, S., Gombos, Z., Veijola, R., Knip, M., Simell, O., Vaarala, O., Åkerblom, H. K., Ilonen, J., Krokowski, M., Bodalski, J., Andrzejewski, W., Ławnik, M., Teodorczyk, A., Heinrich, A., Caillat-Zucman, S., Buzzetti, R., Petrone, A., Mesturino, C., Giorgi, G., Fiori, R., Nisticò, L., Di Genova, G., Cascino, I., Klöting, I., Kovacs, P., McKinney, P. A., Okasha, M., Parslow, R. C., Law, G. R., Gurney, K. A., Williams, R., Bodansky, H. J., Herzig, P., Giani, G., Vervoort, G., Lutterman, J. A., Berden, J. H. M., Wetzels, J. F. 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C., Kaya, F., Süsleyici, B., Öztürk, M., Eisner, M., Guldbakke, B., Karpenko, N., Brizgalova, G., Alesina, M., Røder, M. E., Schwartz, R. S., Prigeon, R., Kahn, S. E., Kendereški, A., Micić, D., Šumarac, M., Macut, Dj., Zonć, S., Čolić, M., Cvijović, G., Gligorović, P., Courtney, C. H., Atkinson, A. B., Ennis, C., Sheridan, B., Bell, P. M., Jolly, M., Amin, R., Godsland, I., Horvoka, R., Anyaoku, V., Lawrence, N., Krasova, N., Sergienko, L., Mingrone, G., Plat, L., Balasse, E. O., Zykova, T., Jenssen, T., Strelkova, A., Zykova, S., Tipisova, E., Féry, F., Wijenaike, A. N., Watt, P. W., Jung, R. T., Bolton-Smith, C., Rennie, M. J., Ludvik, B., Aigmueller, Th., Waldhaeusl, W., Courtois, P., Bource, F., Guenat, E., Philippe, J., Jéquier, E., Tappy, L., Benny, Santosa, Grönemeyer, Dietrich, Aygen, Sitke, Scholz, Nicole, Busch, Martin, Tauveron, I., Rochon, C., Dejax, C., Benoit, P., Capitan, P., Bayle, G., Prugnaud, J., Fabricio, A., Champredon, C., Thieblot, P., Grizard, J., Nielsen, M. F., Nyholm, B., Chandramouli, V., Schumann, W. C., Landau, B. R., Rizza, R. A., Mitrakou, A., Meyer, C., Tolias, A., Platanisiotis, D., Vlachos, L., Gerich, J., Wajngot, A., Sprangers, F., Jellema, W. T., Lopuhaä, C. E., van Lieshout, J. J., van der Zee, J. S., Mithieux, G., Croset, M., Zitoun, C., Hurot, J. M., Rajas, F., Montano, S., Willem, R., Verbruggen, I., Grue-Sørensen, G., Björkling, F., Watson, N. D., Burns, S. P., Murphy, H. C., Iles, R. A., Cohen, R. D., Rooney, K., Swan, V., Phuyal, J., Millar, J., Bryson, J., Denyer, G., Caterson, I., Thompson, C., Gaster, M., Handberg, Aa., Schrøder, H. D., Alzaid, A., Sobki, S., Thye-Rønn, P., Alford, F., Christopher, M., Gras, F., Brunmair, B., Neschen, S., Py, G., Lambert, K., Raynaud, E., Mercier, J., Tsuchihashi, K., Sumida, Y., Fujimoto, H., Nakamura, M., Miyata, E., Furuta, M., Katsuki, A., Ito, K., Sasaki, R., Hori, Y., Yano, Y., Adachi, Y., Lauritz, J., Eriksson, J. W., Burén, J., Zhao, L. J., Li, Z.-C., Kullin, M., Karlsson, F. A., Redondo, A., Puente, J., Clemente, F., González, N., Moberg, E., Amer, P., Hagström-Toft, E., Bolinder, J., Björnholm, M., Krook, A., Galuska, D., Myers, M., Zierath, J. R., Wallberg-Henriksson, H., Niklasson, M., Strindberg, L., Sternberg, F., Hebeda, S., Kratzer, W., Salgado, M. I., Hoss, U., Kalatz, B., Lohmann, S., Fussgänger, R., Khomazjuk, A. I., Ncscheret, A. P., Gonchar, I. V., Quinones-Galvan, A., Sironi, A. M., Cominacini, L., Nagai, Y., Yamashita, H., Takamura, T., Kobayashi, K., Szanto, I., Peth, J. A., Kinnick, T. R., Youngblood, E. B., Tritschler, H. J., Henriksen, E. J., Gašperíková, D., Rufo, C., Teran-Garcia, M., Nakamura, M. T., Clarke, S. D., Pye, S., Zhang, Z., Radziuk, J., Guignot, L., Bell, K. S., Lim-Fraser, M., Cooney, G., Kraegen, E. W., Takayama, S., Legare, D. J., Macedo, M. P., Lautt, W. W., Bradley, B., Barron, P., Davies, J., Ader, M., Richey, J. M., Ait El Mkadem, S., Macari, F., Renard, E., Méchaly, I., Brun, J. F., Cros, G., Bringer, J., del Aguila, L. F., Krishnan, R. K., Farrell, P. A., Ulbrecht, J., Correll, P. H., Kirwan, J. P., Mei, J., Rahn-Landström, T., Brindley, D., Manganiello, V., Degerman, E., Ziv, E., Shafrir, E., Kaiman, R., Galer, S., Bar-On, H., Gerő, L., Földes, K., Janssen, J., Járay, J., Perner, F., Haap, M., Houdali, B., Schmit, M. B., Dietze, G. J., Perrini, S., Natalicchio, A., Montrone, C., de Robertis, O., De Pergola, G., Strack, V., Kellerer, M., Kausch, C., Condorelli, G., Beguinot, F., Häring, H.-U., Song, X. M., Chibalin, A. V., Ryder, J. W., Jiang, X. J., Alessi, D. R., Hennige, A. M., Metzinger, E., Seipke, G., Trüb, T., Hey, A., Sørensen, A. R., Schäffer, L., Drejer, K., Kurtzhals, P., Hansen, B. F., Matozaki, T., Noguchi, T., Yamao, T., Takada, T., Ochi, F., Takeda, H., Inagaki, K., Hosoka, T., Kasuga, M., Schürt, M., Meier, M., Drenckhan, M., Meyer, M., Aries, S. P., Klein, H. H., Telting, D., van der Zon, G. C. M., Dorrestijn, J., Maassen, J. A., Clapham, J. C., Holder, J. C., Tomlinson, K. M., Pickavance, L., Buckingham, R., Wilding, J., Jacinto, S. M., Harrold, J., Ljung, B., Kjellstedt, A., Thalén, P., Widdowson, P., Williams, G., Oakes, N., Aoki, K., Saito, T., Satoh, S., Mukasa, K., Kaneshiro, M., Kawasaki, S., Hoshino, K., Okamura, A., Sekihara, H., Smith, U., Johansson, A., Nilsson, E., Olausson, T., Nakazawa, T., Suzuki, M., Martinez, J., Murado, P., Azal, Ö., Yönem, A., Çakır, B., Polat, Z., Kutlu, M., Çorakçı, A., Bayraktar, M., Gürlek, A., Koray, Z., Damian, M. S., Linn, T., Laube, H., Arzner, S., Meißner, H.-P., Giunti, S., Comune, M., Cassader, M., Conte, M. R., Sacchi, C., Musso, G., Mecca, F., Depetris, N., Gambino, R., Perin, P. Cavallo, Kawakami, S., Sandqvist, M., Jansson, P.-A., Šindelka, G., Widimský, J., Haas, T., Prázný, M., Mari, A., Nolan, J. J., Uusitupa, M. I. J., Karşıdağ, K., Hacıhanefioğlu, B., Dinççağ, N., Drivsholm, T., Palacios, R. T., Vølund, A., Pedersen, Oluf B., Letiexhe, M. R., Scheen, A. J., Quiñones Galvan, A., Simeoni, M., Basu, A., Uosukainen, A., Mäkimattila, S., Schlenzka, A., Adler, A. I., Levy, J., Stevens, R., Matthews, D., Holman, R., Boland, B. J., Jeanjean, M., Hermans, M. P., Maudoigt, C., Tonglet, R., Robert, A., Quiñones-Galvan, A., Cini, G., Galetta, F., Sanna, G., Gernone, F., Janssen, M. J., Gonera, R. K., Wolffenbuttel, B. H. R., de Leeuw, P. W., Schaper, N. C., Molęda, P., Kuczerowski, R., Czech, A., Tatoń, J., Taddei, S., Patiag, D., Qu, X., Wilkes, M., Gray, S., Seale, J. P., Donnelly, R., Campión, J., Maestro, B., Dávila, N., Carranza, M. C., Calle, C., Hales, C. N., Fernández-Real, J. M., Grasa, M., Pugeat, M., Barret, C., Ricart, W., Lindmark, S., Olsson, T., Tufvesson, M., Loeblein, K., Mehnert, B., Haering, H. U., Rave, Klaus, Heise, Tim, Clauson, Per, Hirschberger, Sabine, Heinemann, Lutz, Claret, M., Nadal, B., Truc, A., Rossi, L., Hildebrand, P., Ketterer, S., Beglinger, C., Keller, U., Gyr, K., Parvin, S., Overkamp, D., Vayreda, M., González-Huix, F., G-Huix, F., Zavaroni, I., Gasparini, P., Massironi, P., Zuccarelli, A., Delsignore, R., Reaven, G. M., Sheu, W. H. H., Lee, W. J., Chen, Y.-T., Iraklianou, S., Tournis, S., Volonakis, I., Spylopoulou, M., Bilianou, E., Melidonis, A., Foussas, S., Güler, Serdar, çakir, Bekir, Demi̇rbaş, Berrin, Gürsoy, Gül, Serter, Rüştü, Aral, Yalçin, Morton, G., Lee, S., Fahey, R., de Silva, A., Cai, X. J., Buckingham, R. E., Arch, J. R. S., Wilson, S., Clausen, J. T., Kristensen, P., Nielsen, P. F., Wulff, B. S., Thim, L., Holness, M. J., Sugden, M. C., Fryer, L. G. D., Munns, M. J., Mannucci, E., Ognibene, A., Cremasco, F., Bardini, G., Mencucci, A., Ciani, S., Pierazzuoli, E., Tsuchihashil, K., Rigalleau, V., Delafaye, C., Baillet, L., Vergnot, V., Brunou, P., Gatta, B., Gin, H., Felber, J. P., Munger, R., Assimacopoulos, F., Bobbioni, E., Golay, A., Wilken, M., Larsen, F. S., Buckley, D., Molina, L. M., Marquez, L., Arbeo, A., Hernandez, C., Kofod, H., Damholt, A. B., Buchan, A., Márquez, L., Luque, M. A., Sarti, L., Sutton, P. J., Behle, K., Heimesaat, M. M., Hüfner, M., Gravholt, Claus Højbjerg, Mølier, Niels, Christiansen, Jens Sandahl, Schmitz, Ole, Deacon, C. F., Brock, B., Knudsen, L. B., Agersø, H., Huusfeldt, P. O., Kelly, C. M. N., Brunn, C., Schioos, J., Sewing, S., Lemansky, P., Wawro, S., Mest, H. J., Taguchi, T., Motoshima, H., Yoshizato, K., Guenifi, Amel, Henriksson, M., Johansson, J., Shafqat, J., Tally, M., Wahren, J., Jömvall, H., Ekberg, K., Rigler, R., Pramanik, A., Kratz, G., Johansson, B.-L., Uhlén, M., Jörnvall, H., Forst, T., Dufayet De La Tour, D., Kunt, T., Pfützner, A., Goitom, K., Pohlmann, T., Schneider, S., Johansson, B. L., Löbig, M., Engelbach, M., Beyer, J., Ekman, Bertil, Nyström, Fredrik, Arnqvist, Hans J., Halvatsiotis, P. G., Meek, S., Bigelow, M., Nair, K. S., Maghsoudi, S., Fisker, S., Vølund, A. A., Jörgensen, J. O. L., Christiansen, J. S., Hilsted, J., Mazerkina, N. A., Tiulpakov, A. N., Gorelyshev, S. K., Peterkova, V. A., Macut, D. J., Dieguez, C., Casanueva, F. F., Catalina, P. F., Mallo, F., Andrade, A., García-Mayor, R. V. G., Popova, V. V., ter Maaten, J. C., Popp-Snijders, C., Madsen, L., Ukropec, J., Bergene, E., Rnstan, A. C., Berge, R., Arner, P., Wahl, G., Häring, H., Bryson, J. M., Curtis, S. E., Caterson, I. D., Winzell, M. Sörhede, Svensson, H., Ahnén, B., Holm, C., Phillips, C., Madigan, C., Owens, D., Collins, P., Johnson, A., Tomkin, G. H., Cabezas, M. Castro, van Oostrom, A. J. H. H. M., Erkelens, D. W., Summers, L. K. M., Fielding, B. A., Ilic, V., Clark, M. L., Frayn, K. N., Pietzsch, J., Julius, U., Nitzsche, S., Fischer, S., Lindgren, C., Amrot-Fors, L., Hoffmann, M. M., Luft, D., Schmülling, R.-M., D’Adamo, M., Leonetti, F., Paoloni, A., Ribaudo, M. C., Basso, M. S., Elmore, U., Restuccia, A., Sbraccia, P., Emilsson, V., O’Dowd, J., Heyman, R., Cawthorne, M. A., Pelikánová, T., Kazdová, L., Žák, A., Chvojková, Š., Özer, E. M., Kadıoğlu, P., Korugan, Ü., Hatemi, H., Rivellese, A. A., Dullaart, R. P. F., Riemens, S. C., Sluiter, W. J., van Tol, A., Farnier, M., Megnien, S., Turpin, G., Stulp, B. K., Brambilla, P., Brunelli, A., Riva, M. C., Manzoni, P., de Poli, S., Riboni, S., Stolk, R. P., Meijer, R., Wink, O., Zelissen, P. M. J., van Gils, A. P. G., Grobbee, D. 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W., Taverna, M., Guerre-Millo, M., Chevalier, A., Pacher, N., Slama, G., Gorshunska, M., Buyken, A. E., Heitkamp, G., Kabir, M., Oppert, J. M., Wursch, P., Bruzzo, F., Rahman, M. H., Fatima, K., Ahmed, S., Mondal, H. N., Yilmaz, M., Öztok, U., Karakoç, A., Çakır, N., Düzgün, E., Yetkin, İ., Arslan, M., Şardaş, S., Wilding, John, Géloën, A., Baret, G., Dalmaz, Y., Peyronnet, J., Clémenceau, B., Martignat, L., Lalain, S., Gouin, E., Kenda-Ropson, N., Miller, A. O. A., You, S., Aguilera, E., Recasens, M., Flores, L., Ricart, M. J., Fernández-Cruz, L., Esmatjes, E., Crenier, L., Noël, C., Le Moine, A., Mahy, M., Danguy, A., Kiss, R., Goldman, M., Bracci, C., De Haan, B., Nilsson, K., Deschamps, J. Y., Glagoličová, A., Smrčková, I., Dieterle, C., Illner, W. D., Land, W., Feldmeier, H., Scheuer, R., Lalli, C., Di Loreto, C., Ellringmann, U., Balks, H. J., v. zur Mühlen, A., Dengler, R., Weissenborn, K., Rasmussen, B. M., Ørskov, L., Watson, J., Owen, G., Barrett, G., Ingleby, J., Weiss, M., Deary, I., Cavan, D., Kerr, D., Bruneiii, A., Cuce’, A., Elsing, H. G., Kühne, D., Quinn, N. D., Warner, D. P., Buysschaert, M., Jamal, R., O’Brien, T., Latare, P., Mullen, J., Rein, A., Wargo, M., Parkes, J. L., Ginsberg, B., Sotiropoulos, A., Peppas, Th. A., Kotsini, V., Apostolou, O., Bousboulas, S., Michailidis, E., Sawala, M., Pappas, S., Nilsson, P. M., Nilsson, J. Å., Berglund, G., Molins, T., Esteban, J. I., Genescà, J., Paris, I., Haufroid, V., Selvais, Ph., Petit, J. M., Duong, M., Grappin, M., Guiguet, M., Rudoni, S., Portier, H., Brun, J. M., Bagg, W., Plank, L., Drury, P. L., Sharpe, N., Braatvedt, G. D., Carrascosa, J. M., Molero, J. C., Fermίn, Y., Andrés, A., Satrústegui, J., Rietzsch, H., Patzak, A., Schwanebeck, U., Simpson, H., Robertson-Mackay, F., Montegriffo, E., Fox, C., Chiasson, J.-L., Josse, R. G., Dorman, J. M., Gerstein, H. C., Lau, D., Leiter, L. A., Maheux, P., Meneilly, G. S., Murphy, L., Rodger, N. W., Ross, S. A., Ryan, E., Yale, J.-F., Wolever, T. M. S., Haller, T., Elias, I., Segal, P., Standi, E., Rybka, J., Sencer, E., Satman, I., Schlcnzka, A., Vakkilainen, J., Tsaglis, H., Ioannidis, I., Giakoumaki, A., Amantou, A., Komitopoulos, N., Georgiou, S., Varsamis, E., Katsilambros, N., El Gayar, M., Shereba, N., Botros, R., Fikry, R., Jackson, D., Balme, M., Silva-Nunes, J., Alves, J., Bogalho, P., Gardete-Correia, L., Nunes-Corrêa, J., Kot’átková, A., Němcová, D., Vrbíková, J., Zamrazil, V., Meyer, L., Delbachian, I., Lehert, P., Cugnardey, N., Drouin, P., Guerci, B., Wagner, O. F., Jones, N. P., Vallance, S. E., Thompson, K. A., Miller, A. K., Inglis, A. M. L., Patterson, S., Jorkasky, D., Freed, M. I., Mathisen, A. L., Schneider, R., Rubin, C., Houser, V., Beebe, K. L., Kortboyer, J. M., Eckland, D. J. A., Cranmer, H., Mori, Y., Kurokawa, N., Komiya, H., Horikoshi, H., Yokoyama, J., Tajima, N., Ikeda, Y., Bakst, A., Hemyari, P., Lönnqvist, F., Owen, S., Vikramadithyan, R. K., Chakrabarti, R., Misra, P., Prem Kumar, M., Sunil Kumar, K. B., Ghosh, A., Rajagopalan, R., Goldstein, B., Katoh, S., Tsuruoka, N., Hata, S., Matsushima, M., Ikemoto, S., Inoue, Y., Edwards, G., Fonseca, V., Biswas, N., Bakris, G., Viberti, G., Rebuck, A. S., Weill, S., Abel, M. G., Klappoth, W., Brodesser, A., Linkeschowa, R., Pushparaj, P., Tan, C. H., Tan, B. K. H., Bahner, A., Parker, J., Waite, G., Lipson, V., Nahar, N., Rokeya, B., Parveen, S., Nur-e-Alam, M., Mosihuzzaman, M., Hansen, A. Kornerup, Lepore°, M., Kurzhals, R., Pampanelli°, S., Fanelli°, C. G., Bolli°, G. B., Ratner, R. E., Hirsch, I. B., Mecca, T. E., Wilson, C. A., Mohideen, P., Mudaliar, S., Deutsch, R., Ciaraldi, T., Armstrong, D., Kim, B., Morrill, B., Sha, X., Henry, R., Meyer, B. H., Scholtz, H. 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- Published
- 1999
- Full Text
- View/download PDF
3. Human aging is associated with altered TNF-alpha production during hyperglycemia and hyperinsulinemia.
- Author
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Kirwan JP, Krishnan RK, Weaver JA, Del Aguila LF, and Evans WJ
- Subjects
- Adult, Aged, Blood Glucose physiology, Body Composition, Body Mass Index, C-Peptide blood, Female, Glucose Clamp Technique, Humans, Insulin blood, Islets of Langerhans metabolism, Male, Monocytes metabolism, Aging physiology, Hyperglycemia metabolism, Hyperinsulinism metabolism, Tumor Necrosis Factor-alpha biosynthesis
- Abstract
Changes in tumor necrosis factor-alpha (TNF-alpha) may provide a mechanism to explain impaired glucose metabolism with advancing age. Hyperglycemic clamps (180 min, 10 mM) were performed on seven older [67 +/- 2 yr; body mass index (BMI) 24.7 +/- 1.0 kg/m(2)] and seven younger (22 +/- 1 yr; BMI 21.8 +/- 1.3 kg/m(2)) healthy sedentary males with normal glucose tolerance. TNF-alpha production at basal and at the end of 180 min of hyperglycemia and hyperinsulinemia was measured ex vivo from lipopolysaccharide-stimulated (1 ng/ml) peripheral blood mononuclear cells. Plasma glucose, insulin, and C-peptide levels were similar in both groups at basal and during the last 30 min of the hyperglycemic clamp. Glucose infusion rates were lower (P < 0.004) in the older group compared with the young, indicating decreased insulin action among the older subjects. Basal TNF-alpha secretion was similar in older and younger subjects. TNF-alpha was suppressed (P < 0.02) in the younger group (230 +/- 46 vs. 126 +/- 49 pg/ml; basal vs. clamp) but not in the older group (153 +/- 37 vs. 182 +/- 42 pg/ml), with significant group differences in response (P < 0.05). A significant correlation was observed between the level of suppression in TNF-alpha production and insulin action (Kendall's rank, tau = 0.40, P < 0.05). Furthermore, the TNF-alpha response during the clamp was related to fat mass (r = 0.88, P < 0.001) and abdominal fat (r = 0.81, P < 0.003). In conclusion, these findings suggest a possible mechanism by which TNF-alpha may modulate glucose metabolism in younger people. Aging and modest increases in adiposity prevent the "normal" suppression of TNF-alpha production after a sustained postprandial-like hyperglycemic-hyperinsulinemic stimulus, which may contribute in part to the decline in insulin sensitivity in older men.
- Published
- 2001
- Full Text
- View/download PDF
4. Insulin and exercise differentially regulate PI3-kinase and glycogen synthase in human skeletal muscle.
- Author
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O'Gorman DJ, Del Aguila LF, Williamson DL, Krishnan RK, and Kirwan JP
- Subjects
- Adult, Biopsy, Blood Glucose metabolism, Body Mass Index, Calorimetry, Indirect, Energy Intake, Fasting, Humans, Hyperinsulinism, Insulin blood, Insulin Receptor Substrate Proteins, Insulin Secretion, Male, Muscle, Skeletal cytology, Oxygen Consumption, Phosphoproteins metabolism, Posture, Running, Dietary Carbohydrates, Exercise physiology, Glycogen Synthase metabolism, Insulin metabolism, Muscle, Skeletal enzymology, Phosphatidylinositol 3-Kinases metabolism, Physical Exertion physiology
- Abstract
The purpose of this study was to determine the separate and combined effects of exercise and insulin on the activation of phosphatidylinositol 3-kinase (PI3-kinase) and glycogen synthase in human skeletal muscle in vivo. Seven healthy men performed three trials in random order. The trials included 1) ingestion of 2 g/kg body wt carbohydrate in a 10% solution (CHO); 2) 75 min of semirecumbent cycling exercise at 75% of peak O(2) consumption; followed by 5 x 1-min maximal sprints (Ex); and 3) Ex, immediately followed by ingestion of the carbohydrate solution (ExCHO). Plasma glucose and insulin were increased (P < 0.05) at 15 and 30 (Post-15 and Post-30) min after the trial during CHO and ExCHO, although insulin was lower for ExCHO. Hyperinsulinemia during recovery in CHO and ExCHO led to an increase (P < 0.001) in PI3-kinase activity at Post-30 compared with basal, although the increase was lower (P < 0. 004) for ExCHO. Furthermore, PI3-kinase activity was suppressed (P < 0.02) immediately after exercise (Post-0) during Ex and ExCHO. Area under the insulin response curve for all trials was positively associated with PI3-kinase activity (r = 0.66, P < 0.001). Glycogen synthase activity did not increase during CHO but was increased (P < 0.05) at Post-0 and Post-30 during Ex and ExCHO. Ingestion of the drink increased (P < 0.05) carbohydrate oxidation during CHO and ExCHO, although the increase after ExCHO was lower (P < 0.05) than CHO. Carbohydrate oxidation was directly correlated with PI3-kinase activity for all trials (r = 0.63, P < 0.001). In conclusion, under resting conditions, ingestion of a carbohydrate solution led to activation of the PI3-kinase pathway and oxidation of the carbohydrate. However, when carbohydrate was ingested after intense exercise, the PI3-kinase response was attenuated and glycogen synthase activity was augmented, thus facilitating nonoxidative metabolism or storage of the carbohydrate. Activation of glycogen synthase was independent of PI3-kinase.
- Published
- 2000
- Full Text
- View/download PDF
5. Muscle damage impairs insulin stimulation of IRS-1, PI 3-kinase, and Akt-kinase in human skeletal muscle.
- Author
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Del Aguila LF, Krishnan RK, Ulbrecht JS, Farrell PA, Correll PH, Lang CH, Zierath JR, and Kirwan JP
- Subjects
- Adult, Blood Glucose analysis, Cytokines biosynthesis, Exercise, Fasting blood, Humans, Insulin blood, Insulin Receptor Substrate Proteins, Male, Muscle, Skeletal metabolism, Pain physiopathology, Proto-Oncogene Proteins c-akt, Signal Transduction physiology, Insulin physiology, Muscle, Skeletal physiopathology, Phosphatidylinositol 3-Kinases metabolism, Phosphoproteins metabolism, Protein Serine-Threonine Kinases, Proto-Oncogene Proteins metabolism
- Abstract
Physiological stress associated with muscle damage results in systemic insulin resistance. However, the mechanisms responsible for the insulin resistance are not known; therefore, the present study was conducted to elucidate the molecular mechanisms associated with insulin resistance after muscle damage. Muscle biopsies were obtained before (base) and at 1 h during a hyperinsulinemic-euglycemic clamp (40 mU x kg(-1) x min(-1)) in eight young (age 24+/-1 yr) healthy sedentary (maximal O(2) consumption, 49.7+/-2.4 ml x kg(-1) x min(-1)) males before and 24 h after eccentric exercise (ECC)-induced muscle damage. To determine the role of cytokines in ECC-induced insulin resistance, venous blood samples were obtained before (control) and 24 h after ECC to evaluate ex vivo endotoxin-induced mononuclear cell secretion of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and IL-1beta. Glucose disposal was 19% lower after ECC (P<0.05). Insulin-stimulated insulin receptor substrate (IRS)-1 tyrosine phosphorylation was 45% lower after ECC (P<0.05). Insulin-stimulated phosphatidylinositol (PI) 3-kinase, Akt (protein kinase B) serine phosphorylation, and Akt activity were reduced 34, 65, and 20%, respectively, after ECC (P < 0.05). TNF-alpha, but not IL-6 or IL-1beta production, increased 2.4-fold 24 h after ECC (P<0.05). TNF-alpha production was positively correlated with reduced insulin action on PI 3-kinase (r = 0.77, P = 0.04). In summary, the physiological stress associated with muscle damage impairs insulin stimulation of IRS-1, PI 3-kinase, and Akt-kinase, presumably leading to decreased insulin-mediated glucose uptake. Although more research is needed on the potential role for TNF-alpha inhibition of insulin action, elevated TNF-alpha production after muscle damage may impair insulin signal transduction.
- Published
- 2000
- Full Text
- View/download PDF
6. Regular exercise enhances insulin activation of IRS-1-associated PI3-kinase in human skeletal muscle.
- Author
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Kirwan JP, del Aguila LF, Hernandez JM, Williamson DL, O'Gorman DJ, Lewis R, and Krishnan RK
- Subjects
- Adult, Blood Glucose drug effects, Blood Glucose metabolism, Enzyme Activation drug effects, Female, Glucose pharmacology, Humans, Infusions, Intravenous, Insulin blood, Insulin Receptor Substrate Proteins, Male, Muscle, Skeletal metabolism, Exercise physiology, Insulin pharmacology, Muscle, Skeletal drug effects, Phosphatidylinositol 3-Kinases metabolism, Phosphoproteins metabolism
- Abstract
Insulin action in skeletal muscle is enhanced by regular exercise. Whether insulin signaling in human skeletal muscle is affected by habitual exercise is not well understood. Phosphatidylinositol 3-kinase (PI3-kinase) activation is an important step in the insulin-signaling pathway and appears to regulate glucose metabolism via GLUT-4 translocation in skeletal muscle. To examine the effects of regular exercise on PI3-kinase activation, 2-h hyperinsulinemic (40 mU. m(-2). min(-1))-euglycemic (5.0 mM) clamps were performed on eight healthy exercise-trained [24 +/- 1 yr, 71.8 +/- 2.0 kg, maximal O(2) uptake (VO(2 max)) of 56.1 +/- 2.5 ml. kg(-1). min(-1)] and eight healthy sedentary men and women (24 +/- 1 yr, 64.7 +/- 4.4 kg, VO(2 max) of 44.4 +/- 2.7 ml. kg(-1). min(-1)). A [6, 6-(2)H]glucose tracer was used to measure hepatic glucose output. A muscle biopsy was obtained from the vastus lateralis muscle at basal and at 2 h of hyperinsulinemia to measure insulin receptor substrate-1(IRS-1)-associated PI3-kinase activation. Insulin concentrations during hyperinsulinemia were similar for both groups (293 +/- 22 and 311 +/- 22 pM for trained and sedentary, respectively). Insulin-mediated glucose disposal rates (GDR) were greater (P < 0.05) in the exercise-trained compared with the sedentary control group (9.22 +/- 0.95 vs. 6.36 +/- 0.57 mg. kg fat-free mass(-1). min(-1)). Insulin-stimulated PI3-kinase activation was also greater (P < 0.004) in the trained compared with the sedentary group (3.8 +/- 0.5- vs. 1.8 +/- 0.2-fold increase from basal). Endurance capacity (VO(2 max)) was positively correlated with PI3-kinase activation (r = 0.53, P < 0.04). There was no correlation between PI3-kinase and muscle morphology. However, increases in GDR were positively related to PI3-kinase activation (r = 0.60, P < 0.02). We conclude that regular exercise leads to greater insulin-stimulated IRS-1-associated PI3-kinase activation in human skeletal muscle, thus facilitating enhanced insulin-mediated glucose uptake.
- Published
- 2000
- Full Text
- View/download PDF
7. Expression of vascular permeability factor/vascular endothelial growth factor by melanoma cells increases tumor growth, angiogenesis, and experimental metastasis.
- Author
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Claffey KP, Brown LF, del Aguila LF, Tognazzi K, Yeo KT, Manseau EJ, and Dvorak HF
- Subjects
- Animals, Cell Division, Endothelial Growth Factors genetics, Humans, Lymphokines genetics, Melanoma genetics, Melanoma physiopathology, Mice, Mice, Nude, Mice, SCID, Neoplasm Metastasis, Oligonucleotides, Antisense genetics, Transfection, Tumor Cells, Cultured, Vascular Endothelial Growth Factor A, Vascular Endothelial Growth Factors, DNA, Complementary genetics, Endothelial Growth Factors biosynthesis, Lymphokines biosynthesis, Melanoma metabolism, Neovascularization, Pathologic metabolism
- Abstract
Vascular permeability factor (VPF)/vascular endothelial growth factor (VEGF) is an angiogenic cytokine expressed by many human and animal tumors. Hypoxia often up-regulates VPF/VEGF expression further. To better define the role of VPF/VEGF in tumor biology, we screened tumorigenic lines for those expressing minimal constitutive and hypoxia-inducible VPF/VEGF. Human melanoma SK-MEL-2 cells best fit these criteria and formed small, poorly vascularized tumors in immunodeficient mice. We transfected SK-MEL-2 cells stably with sense or antisense mouse VPF/VEGF cDNA or with vector alone. Cells transfected with sense VPF/VEGF (V+) expressed and secreted large amounts of mouse VPF/VEGF and formed well-vascularized tumors with hyperpermeable blood vessels and minimal necrosis in nude/SCID mice. Antisense-transfected VPF/VEGF (V-) cells expressed reduced constitutive VPF/VEGF and no detectable mouse VPF/VEGF, and formed small, minimally vascularized tumors exhibiting extensive necrosis. Vector-alone transfectants (N1 cells) behaved like parental cells. V+ cells formed numerous lung tumor colonies in SCID mice, approximately 50-fold more than N1 cells, whereas V- cells formed few or none. These experiments demonstrate that VPF/VEGF promotes melanoma growth by stimulating angiogenesis and that constitutive VPF/VEGF expression dramatically promotes tumor colonization in the lung.
- Published
- 1996
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