This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Chen, D.
Right arrow Articles by Pessin, J. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Chen, D.
Right arrow Articles by Pessin, J. E.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, July 1999, p. 4684-4694, Vol. 19, No. 7
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Osmotic Shock Inhibits Insulin Signaling by Maintaining Akt/Protein Kinase B in an Inactive Dephosphorylated State

Dong Chen,1,2 Raymond V. Fucini,1,2 Ann Louise Olson,1,dagger Brian A. Hemmings,3 and Jeffrey E. Pessin1,*

Department of Physiology and Biophysics1 and Molecular Biology Program,2 The University of Iowa, Iowa City, Iowa 52242, and Friedrich Miescher-Institut, CH-4056 Basel, Switzerland3

Received 2 October 1998/Returned for modification 25 November 1998/Accepted 30 March 1999

We have previously reported that insulin and osmotic shock stimulate an increase in glucose transport activity and translocation of the insulin-responsive glucose transporter isoform GLUT4 to the plasma membrane through distinct pathways in 3T3L1 adipocytes (D. Chen, J. S. Elmendorf, A. L. Olson, X. Li, H. S. Earp, and J. E. Pessin, J. Biol. Chem. 272:27401-27410, 1997). In investigations of the relationships between these two signaling pathways, we have now observed that these two stimuli are not additive, and, in fact, osmotic shock pretreatment was found to completely prevent any further insulin stimulation of glucose transport activity and GLUT4 protein translocation. In addition, osmotic shock inhibited the insulin stimulation of lipogenesis and glycogen synthesis. This inhibition of insulin-stimulated downstream signaling occurred without any significant effect on insulin receptor autophosphorylation or tyrosine phosphorylation of insulin receptor substrate 1 (IRS1). Furthermore, there was no effect on either the insulin-stimulated association of the p85 type I phosphatidylinositol (PI) 3-kinase regulatory subunit with IRS1 or phosphotyrosine antibody-immunoprecipitated PI 3-kinase activity. In contrast, osmotic shock pretreatment markedly inhibited the insulin stimulation of protein kinase B (PKB) and p70S6 kinase activities. In addition, the dephosphorylation of PKB was prevented by pretreatment with the phosphatase inhibitors okadaic acid and calyculin A. These data support a model in which osmotic shock-induced insulin resistance of downstream biological responses results from an inhibition of insulin-stimulated PKB activation.

* Corresponding author. Mailing address: The Department of Physiology and Biophysics, The University of Iowa, Iowa City, IA 52242. Phone: (319) 335-7823. Fax: (319) 335-7330. E-mail: Jeffrey-Pessin{at}uiowa.edu.

dagger Present address: Department of Biochemistry and Molecular Biology, The University of Oklahoma Health Sciences Center, Oklahoma City, OK 73190.

Molecular and Cellular Biology, July 1999, p. 4684-4694, Vol. 19, No. 7
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Bae, E. J., Yang, Y. M., Kim, S. G. (2008). Abrogation of Hyperosmotic Impairment of Insulin Signaling by a Novel Class of 1,2-Dithiole-3-thiones through the Inhibition of S6K1 Activation. Mol. Pharmacol. 73: 1502-1512 [Abstract] [Full Text]  
  • Kuo, Y.-C., Huang, K.-Y., Yang, C.-H., Yang, Y.-S., Lee, W.-Y., Chiang, C.-W. (2008). Regulation of Phosphorylation of Thr-308 of Akt, Cell Proliferation, and Survival by the B55{alpha} Regulatory Subunit Targeting of the Protein Phosphatase 2A Holoenzyme to Akt. J. Biol. Chem. 283: 1882-1892 [Abstract] [Full Text]  
  • Chen, D., Reierstad, S., Lin, Z., Lu, M., Brooks, C., Li, N., Innes, J., Bulun, S. E. (2007). Prostaglandin E2 Induces Breast Cancer Related Aromatase Promoters via Activation of p38 and c-Jun NH2-Terminal Kinase in Adipose Fibroblasts. Cancer Res. 67: 8914-8922 [Abstract] [Full Text]  
  • Guan, L., Song, K., Pysz, M. A., Curry, K. J., Hizli, A. A., Danielpour, D., Black, A. R., Black, J. D. (2007). Protein Kinase C-mediated Down-regulation of Cyclin D1 Involves Activation of the Translational Repressor 4E-BP1 via a Phosphoinositide 3-Kinase/Akt-independent, Protein Phosphatase 2A-dependent Mechanism in Intestinal Epithelial Cells. J. Biol. Chem. 282: 14213-14225 [Abstract] [Full Text]  
  • Aoyagi, T., Birumachi, J.-i., Hiroyama, M., Fujiwara, Y., Sanbe, A., Yamauchi, J., Tanoue, A. (2007). Alteration of Glucose Homeostasis in V1a Vasopressin Receptor-Deficient Mice. Endocrinology 148: 2075-2084 [Abstract] [Full Text]  
  • MacRae, V. E., Farquharson, C., Ahmed, S. F. (2006). The pathophysiology of the growth plate in juvenile idiopathic arthritis. Rheumatology (Oxford) 45: 11-19 [Abstract] [Full Text]  
  • Yasuoka, C., Ihara, Y., Ikeda, S., Miyahara, Y., Kondo, T., Kohno, S. (2004). Antiapoptotic Activity of Akt Is Down-regulated by Ca2+ in Myocardiac H9c2 Cells: EVIDENCE OF Ca2+-DEPENDENT REGULATION OF PROTEIN PHOSPHATASE 2Ac. J. Biol. Chem. 279: 51182-51192 [Abstract] [Full Text]  
  • Thompson, J. E., Thompson, C. B. (2004). Putting the Rap on Akt. JCO 22: 4217-4226 [Abstract] [Full Text]  
  • Portnoy, J., Curran-Everett, D., Mason, R. J. (2004). Keratinocyte Growth Factor Stimulates Alveolar Type II Cell Proliferation through the Extracellular Signal-Regulated Kinase and Phosphatidylinositol 3-OH Kinase Pathways. Am. J. Respir. Cell Mol. Bio. 30: 901-907 [Abstract] [Full Text]  
  • Ono, H., Shimano, H., Katagiri, H., Yahagi, N., Sakoda, H., Onishi, Y., Anai, M., Ogihara, T., Fujishiro, M., Viana, A. Y.I., Fukushima, Y., Abe, M., Shojima, N., Kikuchi, M., Yamada, N., Oka, Y., Asano, T. (2003). Hepatic Akt Activation Induces Marked Hypoglycemia, Hepatomegaly, and Hypertriglyceridemia With Sterol Regulatory Element Binding Protein Involvement. Diabetes 52: 2905-2913 [Abstract] [Full Text]  
  • Liao, Y., Hung, M.-C. (2003). Regulation of the Activity of p38 Mitogen-Activated Protein Kinase by Akt in Cancer and Adenoviral Protein E1A-Mediated Sensitization to Apoptosis. Mol. Cell. Biol. 23: 6836-6848 [Abstract] [Full Text]  
  • Arsham, A. M., Howell, J. J., Simon, M. C. (2003). A Novel Hypoxia-inducible Factor-independent Hypoxic Response Regulating Mammalian Target of Rapamycin and Its Targets. J. Biol. Chem. 278: 29655-29660 [Abstract] [Full Text]  
  • Gual, P., Gonzalez, T., Gremeaux, T., Barres, R., Le Marchand-Brustel, Y., Tanti, J.-F. (2003). Hyperosmotic Stress Inhibits Insulin Receptor Substrate-1 Function by Distinct Mechanisms in 3T3-L1 Adipocytes. J. Biol. Chem. 278: 26550-26557 [Abstract] [Full Text]  
  • Gosmanov, A. R., Schneider, E. G., Thomason, D. B. (2003). NKCC activity restores muscle water during hyperosmotic challenge independent of insulin, ERK, and p38 MAPK. Am. J. Physiol. Regul. Integr. Comp. Physiol. 284: R655-R665 [Abstract] [Full Text]  
  • Leong, M. L. L., Maiyar, A. C., Kim, B., O'Keeffe, B. A., Firestone, G. L. (2003). Expression of the Serum- and Glucocorticoid-inducible Protein Kinase, Sgk, Is a Cell Survival Response to Multiple Types of Environmental Stress Stimuli in Mammary Epithelial Cells. J. Biol. Chem. 278: 5871-5882 [Abstract] [Full Text]  
  • Sbrissa, D., Ikonomov, O. C., Deeb, R., Shisheva, A. (2002). Phosphatidylinositol 5-Phosphate Biosynthesis Is Linked to PIKfyve and Is Involved in Osmotic Response Pathway in Mammalian Cells. J. Biol. Chem. 277: 47276-47284 [Abstract] [Full Text]  
  • Gual, P., Shigematsu, S., Kanzaki, M., Gremeaux, T., Gonzalez, T., Pessin, J. E., Le Marchand-Brustel, Y., Tanti, J.-F. (2002). A Crk-II/TC10 Signaling Pathway Is Required For Osmotic Shock-stimulated Glucose Transport. J. Biol. Chem. 277: 43980-43986 [Abstract] [Full Text]  
  • Kageyama, K., Ihara, Y., Goto, S., Urata, Y., Toda, G., Yano, K., Kondo, T. (2002). Overexpression of Calreticulin Modulates Protein Kinase B/Akt Signaling to Promote Apoptosis during Cardiac Differentiation of Cardiomyoblast H9c2 Cells. J. Biol. Chem. 277: 19255-19264 [Abstract] [Full Text]  
  • Hemi, R., Paz, K., Wertheim, N., Karasik, A., Zick, Y., Kanety, H. (2002). Transactivation of ErbB2 and ErbB3 by Tumor Necrosis Factor-alpha and Anisomycin Leads to Impaired Insulin Signaling through Serine/Threonine Phosphorylation of IRS Proteins. J. Biol. Chem. 277: 8961-8969 [Abstract] [Full Text]  
  • Bourbon, N. A., Sandirasegarane, L., Kester, M. (2002). Ceramide-induced Inhibition of Akt Is Mediated through Protein Kinase Czeta . IMPLICATIONS FOR GROWTH ARREST. J. Biol. Chem. 277: 3286-3292 [Abstract] [Full Text]  
  • Kralik, S. F., Liu, P., Leffler, B. J., Elmendorf, J. S. (2002). Ceramide and Glucosamine Antagonism of Alternate Signaling Pathways Regulating Insulin- and Osmotic Shock-Induced Glucose Transporter 4 Translocation. Endocrinology 143: 37-46 [Abstract] [Full Text]  
  • Lange, K. (2002). Role of microvillar cell surfaces in the regulation of glucose uptake and organization of energy metabolism. Am. J. Physiol. Cell Physiol. 282: C1-C26 [Abstract] [Full Text]  
  • Nadler, S. T., Stoehr, J. P., Rabaglia, M. E., Schueler, K. L., Birnbaum, M. J., Attie, A. D. (2001). Normal Akt/PKB with reduced PI3K activation in insulin-resistant mice. Am. J. Physiol. Endocrinol. Metab. 281: E1249-E1254 [Abstract] [Full Text]  
  • Laviola, L., Belsanti, G., Davalli, A. M., Napoli, R., Perrini, S., Weir, G. C., Giorgino, R., Giorgino, F. (2001). Effects of Streptozocin Diabetes and Diabetes Treatment by Islet Transplantation on In Vivo Insulin Signaling in Rat Heart. Diabetes 50: 2709-2720 [Abstract] [Full Text]  
  • Teruel, T., Hernandez, R., Lorenzo, M. (2001). Ceramide Mediates Insulin Resistance by Tumor Necrosis Factor-{alpha} in Brown Adipocytes by Maintaining Akt in an Inactive Dephosphorylated State. Diabetes 50: 2563-2571 [Abstract] [Full Text]  
  • van Golen, C. M., Schwab, T. S., Ignatoski, K. M. W., Ethier, S. P., Feldman, E. L. (2001). PTEN/MMAC1 Overexpression Decreases Insulin-like Growth Factor-I-mediated Protection from Apoptosis in Neuroblastoma Cells. Cell Growth Differ. 12: 371-378 [Abstract] [Full Text]  
  • Beauloye, C., Bertrand, L., Krause, U., Marsin, A.-S., Dresselaers, T., Vanstapel, F., Vanoverschelde, J.-L., Hue, L. (2001). No-Flow Ischemia Inhibits Insulin Signaling in Heart by Decreasing Intracellular pH. Circ. Res. 88: 513-519 [Abstract] [Full Text]  
  • Janez, A., Worrall, D. S., Olefsky, J. M. (2000). Insulin-Mediated Cellular Insulin Resistance Decreases Osmotic Shock-Induced Glucose Transport in 3T3-L1 Adipocytes. Endocrinology 141: 4657-4663 [Abstract] [Full Text]  
  • Derave, W., Hansen, B. F., Lund, S., Kristiansen, S., Richter, E. A. (2000). Muscle glycogen content affects insulin-stimulated glucose transport and protein kinase B activity. Am. J. Physiol. Endocrinol. Metab. 279: E947-E955 [Abstract] [Full Text]  
  • Kanzaki, M., Watson, R. T., Artemyev, N. O., Pessin, J. E. (2000). The Trimeric GTP-binding Protein (Gq/G11) alpha Subunit Is Required for Insulin-stimulated GLUT4 Translocation in 3T3L1 Adipocytes. J. Biol. Chem. 275: 7167-7175 [Abstract] [Full Text]  
  • Andjelkovic, M., Maira, S.-M., Cron, P., Parker, P. J., Hemmings, B. A. (1999). Domain Swapping Used To Investigate the Mechanism of Protein Kinase B Regulation by 3-Phosphoinositide-Dependent Protein Kinase 1 and Ser473 Kinase. Mol. Cell. Biol. 19: 5061-5072 [Abstract] [Full Text]  
  • Bell, L. M., Leong, M. L. L., Kim, B., Wang, E., Park, J., Hemmings, B. A., Firestone, G. L. (2000). Hyperosmotic Stress Stimulates Promoter Activity and Regulates Cellular Utilization of the Serum- and Glucocorticoid-inducible Protein Kinase (Sgk) by a p38 MAPK-dependent Pathway. J. Biol. Chem. 275: 25262-25272 [Abstract] [Full Text]  
  • Yamada, T., Katagiri, H., Asano, T., Inukai, K., Tsuru, M., Kodama, T., Kikuchi, M., Oka, Y. (2001). 3-Phosphoinositide-dependent Protein Kinase 1, an Akt1 Kinase, Is Involved in Dephosphorylation of Thr-308 of Akt1 in Chinese Hamster Ovary Cells. J. Biol. Chem. 276: 5339-5345 [Abstract] [Full Text]  
  • Li, D., Randhawa, V. K., Patel, N., Hayashi, M., Klip, A. (2001). Hyperosmolarity Reduces GLUT4 Endocytosis and Increases Its Exocytosis from a VAMP2-independent Pool in L6 Muscle Cells. J. Biol. Chem. 276: 22883-22891 [Abstract] [Full Text]  
  • Fujishiro, M., Gotoh, Y., Katagiri, H., Sakoda, H., Ogihara, T., Anai, M., Onishi, Y., Ono, H., Funaki, M., Inukai, K., Fukushima, Y., Kikuchi, M., Oka, Y., Asano, T. (2001). MKK6/3 and p38 MAPK Pathway Activation Is Not Necessary for Insulin-induced Glucose Uptake but Regulates Glucose Transporter Expression. J. Biol. Chem. 276: 19800-19806 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»