HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 275, Issue 21, 15765-15772, May 26, 2000

This Article Full Text Full Text (PDF) All Versions of this Article: 275/21/15765    most recent M910002199v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Oreña, S. J. Articles by Garofalo, R. S. Search for Related Content PubMed PubMed Citation Articles by Oreña, S. J. Articles by Garofalo, R. S. Social Bookmarking                      What's this?

Inhibition of Glycogen-synthase Kinase 3 Stimulates Glycogen Synthase and Glucose Transport by Distinct Mechanisms in 3T3-L1 Adipocytes^*

Stephen J. Oreña, Anthony J. Torchia, and Robert S. Garofalo

From Pfizer, Inc., Central Research Division, Groton, Connecticut 06340-8002

The role of glycogen-synthase kinase 3 (GSK3) in insulin-stimulated glucose transport and glycogen synthase activation was investigated in 3T3-L1 adipocytes. GSK3 protein was clearly present in adipocytes and was found to be more abundant than in muscle and liver cell lines. The selective GSK3 inhibitor, LiCl, stimulated glucose transport and glycogen synthase activity (20 and 65%, respectively, of the maximal (1 µM) insulin response) and potentiated the responses to a submaximal concentration (1 nM) of insulin. LiCl- and insulin-stimulated glucose transport were abolished by the phosphatidylinositol 3-kinase (PI3-kinase) inhibitor, wortmannin; however, LiCl stimulation of glycogen synthase was not. In contrast to the rapid stimulation of glucose transport by insulin, transport stimulated by LiCl increased gradually over 3-5 h reaching 40% of the maximal insulin-stimulated level. Both LiCl- and insulin-stimulated glycogen synthase activity were maximal at 25 min. However, insulin-stimulated glycogen synthase activity returned to basal after 2 h, coincident with reactivation of GSK3. After a 2-h exposure to insulin, glycogen synthase was refractory to restimulation with insulin, indicating selective desensitization of this pathway. However, LiCl could partially stimulate glycogen synthase in desensitized cells. Furthermore, coincubation with LiCl during the 2 h exposure to insulin completely blocked desensitization of glycogen synthase activity. In summary, inhibition of GSK3 by LiCl: 1) stimulated glycogen synthase activity directly and independently of PI3-kinase, 2) stimulated glucose transport at a point upstream of PI3-kinase, 3) stimulated glycogen synthase activity in desensitized cells, and 4) prevented desensitization of glycogen synthase due to chronic insulin treatment. These data are consistent with GSK3 playing a central role in the regulation of glycogen synthase activity and a contributing factor in the regulation of glucose transport in 3T3-L1 adipocytes.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				S. Patel, B. W. Doble, K. MacAulay, E. M. Sinclair, D. J. Drucker, and J. R. Woodgett Tissue-Specific Role of Glycogen Synthase Kinase 3{beta} in Glucose Homeostasis and Insulin Action Mol. Cell. Biol., October 15, 2008; 28(20): 6314 - 6328. [Abstract] [Full Text] [PDF]

				R. Barillas, I. Friehs, H. Cao-Danh, J. F. Martinez, and P. J. del Nido Inhibition of Glycogen Synthase Kinase-3{beta} Improves Tolerance to Ischemia in Hypertrophied Hearts Ann. Thorac. Surg., July 1, 2007; 84(1): 126 - 133. [Abstract] [Full Text] [PDF]

				S. Vankoningsloo, M. Piens, C. Lecocq, A. Gilson, A. De Pauw, P. Renard, C. Demazy, A. Houbion, M. Raes, and T. Arnould Mitochondrial dysfunction induces triglyceride accumulation in 3T3-L1 cells: role of fatty acid {beta}-oxidation and glucose J. Lipid Res., June 1, 2005; 46(6): 1133 - 1149. [Abstract] [Full Text] [PDF]

				H. Ou, L. Yan, S. Osmanovic, C. C. Greenberg, and M. J. Brady Spatial Reorganization of Glycogen Synthase upon Activation in 3T3-L1 Adipocytes Endocrinology, January 1, 2005; 146(1): 494 - 502. [Abstract] [Full Text] [PDF]

				K. H. Kim, M. J. Song, E. J. Yoo, S. S. Choe, S. D. Park, and J. B. Kim Regulatory Role of Glycogen Synthase Kinase 3 for Transcriptional Activity of ADD1/SREBP1c J. Biol. Chem., December 10, 2004; 279(50): 51999 - 52006. [Abstract] [Full Text] [PDF]

				D. Mottet, V. Dumont, Y. Deccache, C. Demazy, N. Ninane, M. Raes, and C. Michiels Regulation of Hypoxia-inducible Factor-1{alpha} Protein Level during Hypoxic Conditions by the Phosphatidylinositol 3-Kinase/Akt/Glycogen Synthase Kinase 3{beta} Pathway in HepG2 Cells J. Biol. Chem., August 15, 2003; 278(33): 31277 - 31285. [Abstract] [Full Text] [PDF]

				E. J. Henriksen, T. R. Kinnick, M. K. Teachey, M. P. O'Keefe, D. Ring, K. W. Johnson, and S. D. Harrison Modulation of muscle insulin resistance by selective inhibition of GSK-3 in Zucker diabetic fatty rats Am J Physiol Endocrinol Metab, May 1, 2003; 284(5): E892 - E900. [Abstract] [Full Text] [PDF]

				R. R. Gomis, C. Favre, M. Garcia-Rocha, J. M. Fernandez-Novell, J. C. Ferrer, and J. J. Guinovart Glucose 6-Phosphate Produced by Gluconeogenesis and by Glucokinase Is Equally Effective in Activating Hepatic Glycogen Synthase J. Biol. Chem., March 7, 2003; 278(11): 9740 - 9746. [Abstract] [Full Text] [PDF]

				D. B. Ring, K. W. Johnson, E. J. Henriksen, J. M. Nuss, D. Goff, T. R. Kinnick, S. T. Ma, J. W. Reeder, I. Samuels, T. Slabiak, et al. Selective Glycogen Synthase Kinase 3 Inhibitors Potentiate Insulin Activation of Glucose Transport and Utilization In Vitro and In Vivo Diabetes, March 1, 2003; 52(3): 588 - 595. [Abstract] [Full Text] [PDF]

				G. W. Cline, K. Johnson, W. Regittnig, P. Perret, E. Tozzo, L. Xiao, C. Damico, and G. I. Shulman Effects of a Novel Glycogen Synthase Kinase-3 Inhibitor on Insulin-Stimulated Glucose Metabolism in Zucker Diabetic Fatty (fa/fa) Rats Diabetes, October 1, 2002; 51(10): 2903 - 2910. [Abstract] [Full Text] [PDF]

				B. Charrier, A. Champion, Y. Henry, and M. Kreis Expression Profiling of the Whole Arabidopsis Shaggy-Like Kinase Multigene Family by Real-Time Reverse Transcriptase-Polymerase Chain Reaction Plant Physiology, October 1, 2002; 130(2): 577 - 590. [Abstract] [Full Text] [PDF]

				Y.-B. Kim, G. I. Shulman, and B. B. Kahn Fatty Acid Infusion Selectively Impairs Insulin Action on Akt1 and Protein Kinase C lambda /zeta but Not on Glycogen Synthase Kinase-3 J. Biol. Chem., August 30, 2002; 277(36): 32915 - 32922. [Abstract] [Full Text] [PDF]

				S. E. Nikoulina, T. P. Ciaraldi, S. Mudaliar, L. Carter, K. Johnson, and R. R. Henry Inhibition of Glycogen Synthase Kinase 3 Improves Insulin Action and Glucose Metabolism in Human Skeletal Muscle Diabetes, July 1, 2002; 51(7): 2190 - 2198. [Abstract] [Full Text] [PDF]

				P. Boileau, M. Cauzac, M. A. Pereira, J. Girard, and S. Hauguel-de Mouzon Dissociation between Insulin-Mediated Signaling Pathways and Biological Effects in Placental Cells: Role of Protein Kinase B and MAPK Phosphorylation Endocrinology, September 1, 2001; 142(9): 3974 - 3979. [Abstract] [Full Text] [PDF]

				M. M. Monick, A. B. Carter, P. K. Robeff, D. M. Flaherty, M. W. Peterson, and G. W. Hunninghake Lipopolysaccharide Activates Akt in Human Alveolar Macrophages Resulting in Nuclear Accumulation and Transcriptional Activity of {{beta}}-Catenin J. Immunol., April 1, 2001; 166(7): 4713 - 4720. [Abstract] [Full Text] [PDF]

				T. C. Jensen, S. M. Crosson, P. M. Kartha, and M. J. Brady Specific Desensitization of Glycogen Synthase Activation by Insulin in 3T3-L1 Adipocytes. CONNECTION BETWEEN ENZYMATIC ACTIVATION AND SUBCELLULAR LOCALIZATION J. Biol. Chem., December 15, 2000; 275(51): 40148 - 40154. [Abstract] [Full Text] [PDF]