Keywords: Camk, Cellular Signalling, Glucose Uptake, Insulin, Calcium Calmodulin Dependent Protein Kinase Ii, Glucose Transporter 4, Insulin Receptor Substrate 1, Mitogen Activated Protein Kinase 1, Raf Protein, Thymidine, Animal Cell, Article, Cell Membrane, Cell Proliferation, Dna Synthesis, Down Regulation, Enzyme Activation, Enzyme Phosphorylation, Negative Feedback, Nonhuman, Priority Journal, Skeletal Muscle, Biological Transport, Calcium-Calmodulin-Dependent Protein Kinase Type 2, Cell Line, Down-Regulation, Mitogen-Activated Protein Kinase 3, Proto-Oncogene Proteins C-Akt, Proto-Oncogene Proteins C-Raf, Signal Transduction, Rattus,
Affiliations: *** IBB - CNR ***
Department of Biologia e Patologia Cellulare e Molecolare, University of Naples Federico II, Naples, Italy
Institute of Biostrutture e Bioimmagini, University of Naples Federico II, Naples, Italy
Department Medicina Clinica e Scienze Cardiovascolari e Immunologiche, University of Naples Federico II, Naples, Italy
Department of Endocrinologia e Oncologia Molecolare e Clinica, University of Naples Federico II, Naples, Italy
Institute of Endocrinologia e Oncologia Sperimentale, CNR, Naples, Italy
References: White, M.F., (1997) Diabetologia, 40 (SUPPL. 2), pp. S
Illario, M., Amideo, V., Casamassima, A., Andreucci, M., di Matola, T., Miele, C., Rossi, G., Vitale, M., (2003) J. Clin. Endocrinol. Metab., 88 (1), p. 260
Youn, J.H., Gulve, E.A., Henriksen, E.J., Holloszy, J.O., (1994) Am. J. Physiol., 267 (4 PART 2), pp. R888
Young, J.C., Balon, T.W., (1997) Life. Sci., 61 (3), p. 335
Cartee, G.D., Briggs-Tung, C., Holloszy, J.O., (1992) Am. J. Physiol., 263 (1 PART 2), pp. R70
Klip, A., Li, G., Logan, W.J., (1984) Am. J. Physiol., 247 (3 PART 1), pp. E297
Espinosa, A., Estrada, M., Jaimovich, E., (2004) J. Endocrinol., 182 (2), p. 339
Wright, D.C., Fick, C.A., Olesen, J.B., Lim, K., Barnes, B.R., Craig, B.W., (2004) Life. Sci., 74 (7), p. 815
White, M. F., (1997) Diabetologia, 40 (SUPPL. 2), pp. S
Sun, X. J., Rothenberg, P., Kahn, C. R., Backer, J. M., Araki, E., Wilden, P. A., Cahill, D. A., White, M. F., (1991) Nature, 352 (6330), p. 73
Chuang, L. M., Myers Jr., M. G., Seidner, G. A., Birnbaum, M. J., White, M. F., Kahn, C. R., (1993) Proc. Natl. Acad. Sci. U. S. A., 90 (11), p. 5172
Wang, L. M., Myers Jr., M. G., Sun, X. J., Aaronson, S. A., White, M., Pierce, J. H., (1993) Science, 261 (5128), p. 1591
Czech, M. P., Corvera, S., (1999) J. Biol. Chem., 274 (4), p. 1865
Bard-Chapeau, E. A., Hevener, A. L., Long, S., Zhang, E. E., Olefsky, J. M., Feng, G. S., (2005) Nat. Med., 11 (5), p. 567
Pershadsingh, H. A., Gale, R. D., McDonald, J. M., (1987) Endocrinology, 121 (5), p. 1727
Etter, E. F., Minta, A., Poenie, M., Fay, F. S., (1996) Proc. Natl. Acad. Sci. U. S. A., 93 (11), p. 5368
Bruton, J. D., Katz, A., Westerblad, H., (1999) Proc. Natl. Acad. Sci. U. S. A., 96 (6), p. 3281
Means, A. R., (2000) Mol. Endocrinol., 14 (1), p. 4
Matthews, R. P., Guthrie, C. R., Wailes, L. M., Zhao, X., Means, A. R., McKnight, G. S., (1994) Mol. Cell. Biol., 14 (9), p. 6107
Tombes, R. M., Faison, M. O., Turbeville, J. M., (2003) Gene, 322, p. 17
Colomer, J. M., Means, A. R., (2000) Mol. Endocrinol., 14 (8), p. 1125
Hanson, P. I., Kapiloff, M. S., Lou, L. L., Rosenfeld, M. G., Schulman, H., (1989) Neuron, 3 (1), p. 59
Cruzalegui, F. H., Means, A. R., (1993) J. Biol. Chem., 268 (35), p. 26171
Chang, B. H., Mukherji, S., Soderling, T. R., (1998) Proc. Natl. Acad. Sci. U. S. A., 95 (18), p. 10890
Vest, R. S., Davies, K. D., O'Leary, H., Port, J. D., Bayer, K. U., (2007) Mol. Biol. Cell, 18 (12), p. 5024
Youn, J. H., Gulve, E. A., Henriksen, E. J., Holloszy, J. O., (1994) Am. J. Physiol., 267 (4 PART 2), pp. R888
Young, J. C., Balon, T. W., (1997) Life. Sci., 61 (3), p. 335
Cartee, G. D., Briggs-Tung, C., Holloszy, J. O., (1992) Am. J. Physiol., 263 (1 PART 2), pp. R70
Wright, D. C., Fick, C. A., Olesen, J. B., Lim, K., Barnes, B. R., Craig, B. W., (2004) Life. Sci., 74 (7), p. 815
Saltiel, A. R., Kahn, C. R., (2001) Nature, 414 (6865), p. 799
Lee, A. D., Gulve, E. A., Chen, M., Schluter, J., Holloszy, J. O., (1995) Am. J. Physiol., 268 (4 PART 2), pp. R997
Carlson, C. J., Koterski, S., Sciotti, R. J., Poccard, G. B., Rondinone, C. M., (2003) Diabetes, 52 (3), p. 634
Calcium-calmodulin-dependent kinase II (CaMKII) mediates insulin-stimulated proliferation and glucose uptake
Cellular growth and glucose uptake are regulated by multiple signals generated by the insulin receptor. The mechanisms of individual modulation of these signals remain somewhat elusive. We investigated the role of CaMKII in insulin signalling in a rat skeletal muscle cell line, demonstrating that CaMKII modulates the insulin action on DNA synthesis and the negative feedback that down regulates glucose uptake. Insulin stimulation generated partly independent signals leading to the rapid activation of Akt, Erk-1/2 and CaMKII Akt activation was followed by Glut-4 translocation to the plasma membrane and increase of glucose uptake. Then, IRS-1 was phosphorylated at S612, the IRS-1/p85PI3K complex was disrupted, Akt was no more phosphorylated and both Glut-4 translocation and glucose uptake were reduced. Inhibition of CaMKII abrogated the insulin-induced Erk-1/2 activation, DNA synthesis and phosphorylation of IRS-1 at S612. Inhibition of CaMKII also abrogated the down-regulation of insulin-stimulated Akt phosphorylation, Glut-4 membrane translocation and glucose uptake. These results demonstrate that: 1 - CaMKII modulates the insulin-induced Erk-1/2 activation and cell proliferation; 2 - after the initial stimulation of the IRS-1/Akt pathway, CaMKII mediates the down-regulation of stimulated glucose uptake. This represents a novel mechanism in the selective control of insulin signals, and a possible site for pharmacological intervention. (C) 2009 Elsevier Inc. All rights reserved.
Calcium-calmodulin-dependent kinase II (CaMKII) mediates insulin-stimulated proliferation and glucose uptake