Artículos de revistas
Endurance Exercise Training Increases Appl1 Expression And Improves Insulin Signaling In The Hepatic Tissue Of Diet-induced Obese Mice, Independently Of Weight Loss
Registro en:
Journal Of Cellular Physiology. , v. 227, n. 7, p. 2917 - 2926, 2012.
219541
10.1002/jcp.23037
2-s2.0-84858685776
Autor
Marinho R.
Ropelle E.R.
Cintra D.E.
De Souza C.T.
Da Silva A.S.R.
Bertoli F.C.
Colantonio E.
D'Almeida V.
Pauli J.R.
Institución
Resumen
Hepatic insulin resistance is the major contributor to fasting hyperglycemia in type 2 diabetes. The protein kinase Akt plays a central role in the suppression of gluconeogenesis involving forkhead box O1 (Foxo1) and peroxisome proliferator-activated receptor gamma co-activator 1 alpha (PGC-1α), and in the control of glycogen synthesis involving the glycogen synthase kinase beta (GSK3β) in the liver. It has been demonstrated that endosomal adaptor protein APPL1 interacts with Akt and blocks the association of Akt with its endogenous inhibitor, tribbles-related protein 3 (TRB3), improving the action of insulin in the liver. Here, we demonstrated that chronic exercise increased the basal levels and insulin-induced Akt serine phosphorylation in the liver of diet-induced obese mice. Endurance training was able to increase APPL1 expression and the interaction between APPL1 and Akt. Conversely, training reduced both TRB3 expression and TRB3 and Akt association. The positive effects of exercise on insulin action are reinforced by our findings that showed that trained mice presented an increase in Foxo1 phosphorylation and Foxo1/PGC-1α association, which was accompanied by a reduction in gluconeogenic gene expressions (PEPCK and G6Pase). Finally, exercised animals demonstrated increased at basal and insulin-induced GSK3β phosphorylation levels and glycogen content at 24h after the last session of exercise. Our findings demonstrate that exercise increases insulin action, at least in part, through the enhancement of APPL1 and the reduction of TRB3 expression in the liver of obese mice, independently of weight loss. © 2011 Wiley Periodicals, Inc. 227 7 2917 2926 Aoyama, H., Daitoku, H., Fukamizu, A., Nutrient control of phosphorylation and translocation of Foxo1 in C57BL/6 and db/db mice (2006) Int J Mol Med, 18, pp. 433-439 Barthel, A., Schmoll, D., Krüger, K.D., Bahrenberg, G., Walther, R., Roth, R.A., Joost, H.G., Differential regulation of endogenous glucose-6-phosphatase and phosphoenol pyruvate carboxykinase gene expression by the forkhead transcription factor FKHR in H4IIE hepatoma cells (2001) Biochem Biophys Res Commun, 285, pp. 897-902 Bonora, E., Moghetti, P., Zancanaro, C., Cigolini, M., Querena, M., Cacciatori, V., Corgnati, A., Muggeo, M., Estimates of in vivo insulin action in man: Comparison of insulin tolerance tests with euglycemic and hyperglycemic glucose clamp studies (1989) J Clin Endocrinol Metab, 68, pp. 374-378 Bradford, M.M., A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding (1976) Anal Biochem, 72, pp. 248-254 Cheng, K.K., Iglesias, M.A., Lam, K.S.L., Wang, Y., Sweeney, G., Zhu, W., Vanhoutte, P.M., Xu, A., APPL1 potentiates insulin-mediated inhibition of hepatic glucose production and alleviates diabetes via Akt activation in mice (2009) Cell Metab, 9, pp. 417-427 Cheng, Z., Guo, S., Copps, K., Dong, X., Kollipara, R., Rodgers, J.T., Depinho, R.A., White, M.F., Foxo1 integrates insulin signaling with mitochondrial function in the liver (2009) Nat Med, 15, pp. 1307-1311 Cho, H., Mu, J., Kim, J.K., Thorvaldsen, J.L., Chu, Q., Crenshaw, E.B., Kaestner, K.H., Birnbaum, M.J., Insulin resistance and a diabetes mellitus-like syndrome in mice lacking the protein kinase Akt2 (PKB beta) (2001) Science, 292, pp. 1728-1731 Cintra, D.E., Pauli, J.R., Araújo, E.P., Moraes, J.C., de Souza, C.T., Milanski, M., Morari, J., Velloso, L.A., Interleukin-10 is a protective factor against diet-induced insulin resistance in liver (2008) J Hepatol, 48, pp. 628-637 Da Silva, A.S., Pauli, J.R., Ropelle, E.R., Oliveira, A.G., Cintra, D.E., De Souza, C.T., Velloso, L.A., Saad, M.J., Exercise intensity, inflammatory signaling, and insulin resistance in obese rats (2010) Med Sci Sports Exerc, 42, pp. 2180-2188 De Souza, C.T., Araujo, E.P., Bordin, S., Ashimine, R., Zollner, R.L., Boschero, A.C., Saad, M.J., Velloso, L.A., Consumption of a fat-rich diet activates a proinflammatory response and induces insulin resistance in the hypothalamus (2005) Endocrinology, 146, pp. 4189-4191 Dentin, R., Liu, Y., Koo, S.H., Hedrick, S., Vargas, T., Heredia, J., Yates, J., Montminy, M., Insulin modulates gluconeogenesis by inhibition of the coactivator TORC2 (2007) Nature, 449, pp. 366-369 Du, K., Herzig, S., Kulkarni, R.N., Montminy, M., TRB3: A tribbles homolog that inhibits Akt/PKB activation by insulin in liver (2003) Science, 300, pp. 1574-1577 Hegedus, Z., Czibula, A., Kiss-Toth, E., Tribbles: A family of kinase-likeproteins with potent signalling regulatory function (2007) Cell Signal, 19, pp. 238-250 Heled, Y., Shapiro, Y., Shani, Y., Moran, D.S., Langzam, L., Barash, V., Sampson, S.R., Meyerovitch, J., Physical exercise enhances hepatic insulin signaling and inhibits phosphoenolpyruvate carboxykinase activity in diabetes-prone Psammomys obesus (2004) Metabolism, 53, pp. 836-841 Herzig, S., Long, F., Jhala, U.S., Hedrick, S., Quinn, R., Bauer, A., Rudolph, D., Montminy, M., CREB regulates hepatic gluconeogenesis through the coactivator PGC-1 (2001) Nature, 413, pp. 179-183 Hoene, M., Lehmann, R., Hennige, A.M., Pohl, A.K., Häring, H.U., Schleicher, E.D., Weigert, C., Acute regulation of metabolic genes and insulin receptor substrates in the liver of mice by one single bout of treadmill exercise (2009) J Physiol, 587, pp. 241-252 Houmard, J.A., Shaw, C.D., Hickey, M.S., Tanner, C.J., Effect of short-term exercise training on insulin-stimulated PI 3-kinase activity in human skeletal muscle (1999) Am J Physiol, 277, pp. E1055-E1060 Laemmli, U.K., Cleavage of structural proteins during the assembly of the head of bacteriophage T4 (1970) Nature, 227, pp. 680-685 Li, X., Monks, B., Ge, Q., Birnbaum, M.J., Akt/PKB regulates hepatic metabolism by directly inhibiting PGC-1a transcription coactivator (2007) Nature, 447, pp. 1012-1016 Lima, F.A., Ropelle, E.R., Pauli, J.R., Cintra, D.E., Frederico, M.J.S., Pinho, R.A., Velloso, L.A., De Souza, C.T., Acute exercise reduces insulin resistance-induced TRB3 expression and amelioration of the hepatic production of glucose in the liver of diabetic mice (2009) J Cell Physiol, 221, pp. 92-97 Matsushima, R., Harada, N., Webster, N.J., Tsutsumi, Y.M., Nakaya, Y., Effect of TRB3 on insulin and nutrient stimulated hepatic p70 S6 kinase activity (2006) J Biol Chem, 281, pp. 29719-29729 Michael, M.D., Kulkarni, R.N., Postic, C., Previs, S.F., Shulman, G.I., Magnuson, M.A., Kanh, C.R., Loss of insulin signaling in hepatocytes leads to severe insulin resistance and progressive hepatic dysfunction (2000) Mol Cell, 6, pp. 87-97 Mikines, K.J., Sonne, B., Farrell, P.A., Tronier, B., Galbo, H., Effect of physical exercise on sensitivity and responsiveness to insulin in humans (1988) Am J Physiol, 254, pp. E248-E259 Nakae, J., Park, B.C., Accili, D., Insulin stimulates phosphorylation of the forkhead transcription factor FKHR on serine 253 through a Wortmannin-sensitive pathway (1999) J Biol Chem, 274, pp. 15982-15985 O'Gorman, D.J., Karlsson, H.K., McQuaid, S., Yousif, O., Rahman, Y., Gasparro, D., Glund, S., Nolan, J.J., Exercise training increases insulin-stimulated glucose disposal and GLUT4 (SLC2A4) protein content in patients with type 2 diabetes (2006) Diabetologia, 49, pp. 2983-2992 Park, E.J., Lee, J.H., Yu, G.Y., He, G., Ali, S.R., Holzer, R.G., Osterreicher, C.H., Karin, M., Dietary and genetic obesity promote liver inflammation and tumorigenesis by enhancing IL-6 and TNF expression (2010) Cell, 140, pp. 197-208 Perseghin, G., Price, T.B., Petersen, K.F., Roden, M., Cline, G.W., Gerow, K., Rothman, D.L., Shulman, G.I., Increased glucose transport-phosphorylation and muscle glycogen synthesis after exercise training in insulin-resistant subjects (1996) N Engl J Med, 335, pp. 1357-1362 Pimenta, W.P., Saad, M.J., Paccola, G.M., Piccinato, C.E., Foss, M.C., Effect of oral glucose on peripheral muscle fuel metabolism in fasted men (1989) Braz J Med Biol Res, 22, pp. 465-476 Postic, C., Dentin, R., Girard, J., Role of the liver in the control of carbohydrate and lipid homeostasis (2004) Diabet Metab, 30, pp. 398-408 Puigserver, P., Rhee, J., Donovan, J., Walkey, C.J., Yoon, J.C., Oriente, F., Kitamura, Y., Spiegelman, B.M., Insulin-regulated hepatic gluconeogenesis through FOXO1-PGC-1alpha interaction (2003) Nature, 423, pp. 550-555 Rhee, J., Inoue, Y., Yoon, J.C., Puigserver, P., Fan, M., Gonzalez, F.J., Spiegelman, B.M., Regulation of hepatic fasting response by PPARγ coactivator-1α (PGC-1): Requirement for hepatocyte nuclear factor 4α in gluconeogenesis (2003) Proc Natl Acad Sci USA, 100, pp. 4012-4017 Richter, E.A., Mikines, K.J., Galbo, H., Kiens, B., Effect of exercise on insulin action in muscle (1989) J Appl Physiol, 66, pp. 876-885 Röckl, K.S., Witczak, C.A., Goodyear, L.J., Signaling mechanisms in skeletal muscle: Acute responses and chronic adaptations to exercise (2008) IUBMB Life, 60, pp. 145-153 Ropelle, E.R., Pauli, J.R., Cintra, D.E., Frederico, M.J., de Pinho, R.A., Velloso, L.A., De Souza, C.T., Acute exercise modulates the Foxo1/PGC-1alpha pathway in the liver of diet-induced obesity rats (2009) J Physiol, 587, pp. 2069-2076 Schenck, A., Goto-Silva, L., Collinet, C., Rhinn, M., Giner, A., Habermann, B., Brand, M., Zerial, M., The endosomal protein Appl1 mediates Akt substrate specificity and cell survival in vertebrate development (2008) Cell, 133, pp. 486-497 Scott, A.M., Atwater, I., Rojas, E., A method for the simultaneous measurement of insulin release and B cell membrane potential in single mouse islets of Langerhans (1981) Diabetologia, 21, pp. 470-475 Taniguchi, C.M., Kondo, T., Sajan, M., Luo, J., Bronson, R., Asano, T., Farese, R., Kahn, C.R., Divergent regulation of hepatic glucose and lipid metabolism by phosphoinositide 3-kinase via Akt and PKClambda/zeta (2006) Cell Metab, 3, pp. 343-353 Xu, H., Dembski, M., Yang, Q., Yang, D., Moriarty, A., Tayber, O., Chen, H., Tartaglia, L.A., Dual specificity mitogen-activated protein (MAP) kinase phosphatase-4 plays a potential role in insulin resistance (2003) J Biol Chem, 278, pp. 30187-30192 Yoon, J.C., Puigserver, P., Chen, G., Donovan, J., Wu, Z., Rhee, J., Control of hepatic gluconeogenesis through the transcriptional coactivator PGC-1 (2001) Nature, 413, pp. 131-138