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 Lamia, K. A.
Right arrow Articles by Cantley, L. C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lamia, K. A.
Right arrow Articles by Cantley, L. C.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, June 2004, p. 5080-5087, Vol. 24, No. 11
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.11.5080-5087.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Increased Insulin Sensitivity and Reduced Adiposity in Phosphatidylinositol 5-Phosphate 4-Kinase ß–/– Mice

Katja A. Lamia,1 Odile D. Peroni,2 Young-Bum Kim,2 Lucia E. Rameh,3 Barbara B. Kahn,2 and Lewis C. Cantley1*

Division of Signal Transduction, Beth Israel Deaconess Medical Center, and Department of Cell Biology, Harvard Medical School,1 Division of Endocrinology, Diabetes, and Metabolism, Beth Israel Deaconess Medical Center, and Department of Medicine, Harvard Medical School, Boston,2 Boston Biomedical Research Institute, Watertown, Massachusetts3

Received 25 November 2003/ Returned for modification 5 January 2004/ Accepted 16 March 2004

Phosphorylated derivatives of the lipid phosphatidylinositol are known to play critical roles in insulin response. Phosphatidylinositol 5-phosphate 4-kinases convert phosphatidylinositol 5-phosphate to phosphatidylinositol 4,5-bis-phosphate. To understand the physiological role of these kinases, we generated mice that do not express phosphatidylinositol 5-phosphate 4-kinase ß. These mice are hypersensitive to insulin and have reduced body weights compared to wild-type littermates. While adult male mice lacking phosphatidylinositol 5-phosphate 4-kinase ß have significantly less body fat than wild-type littermates, female mice lacking phosphatidylinositol 5-phosphate 4-kinase ß have increased insulin sensitivity in the presence of normal adiposity. Furthermore, in vivo insulin-induced activation of the protein kinase Akt is enhanced in skeletal muscle and liver from mice lacking phosphatidylinositol 5-phosphate 4-kinase ß. These results indicate that phosphatidylinositol 5-phosphate 4-kinase ß plays a role in determining insulin sensitivity and adiposity in vivo and suggest that inhibitors of this enzyme may be useful in the treatment of type 2 diabetes.

* Corresponding author. Mailing address: Beth Israel Hospital, Harvard Institutes of Medicine, Division of Signal Transduction, 10th Floor, 330 Brookline, MA 02215. Phone: (617) 667-0947. Fax: (617) 667-0957. E-mail: lewis_cantley{at}hms.harvard.edu.

Molecular and Cellular Biology, June 2004, p. 5080-5087, Vol. 24, No. 11
0022-538X/04/$08.00+0     DOI: 10.1128/MCB.24.11.5080-5087.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Demian, D. J., Clugston, S. L., Foster, M. M., Rameh, L., Sarkes, D., Townson, S. A., Yang, L., Zhang, M., Charlton, M. E. (2009). High-Throughput, Cell-Free, Liposome-Based Approach for Assessing In Vitro Activity of Lipid Kinases. J Biomol Screen 14: 838-844 [Abstract]  
  • Adochio, R., Leitner, J. W., Hedlund, R., Draznin, B. (2009). Rescuing 3T3-L1 Adipocytes from Insulin Resistance Induced by Stimulation of Akt-Mammalian Target of Rapamycin/p70 S6 Kinase (S6K1) Pathway and Serine Phosphorylation of Insulin Receptor Substrate-1: Effect of Reduced Expression of p85{alpha} Subunit of Phosphatidylinositol 3-Kinase and S6K1 Kinase. Endocrinology 150: 1165-1173 [Abstract] [Full Text]  
  • Clarke, J. H., Emson, P. C., Irvine, R. F. (2008). Localization of phosphatidylinositol phosphate kinase II{gamma} in kidney to a membrane trafficking compartment within specialized cells of the nephron. Am. J. Physiol. Renal Physiol. 295: F1422-F1430 [Abstract] [Full Text]  
  • Shisheva, A. (2008). Phosphoinositides in insulin action on GLUT4 dynamics: not just PtdIns(3,4,5)P3. Am. J. Physiol. Endocrinol. Metab. 295: E536-E544 [Abstract] [Full Text]  
  • Bunce, M. W., Boronenkov, I. V., Anderson, R. A. (2008). Coordinated Activation of the Nuclear Ubiquitin Ligase Cul3-SPOP by the Generation of Phosphatidylinositol 5-Phosphate. J. Biol. Chem. 283: 8678-8686 [Abstract] [Full Text]  
  • Xue, B., Kim, Y.-B., Lee, A., Toschi, E., Bonner-Weir, S., Kahn, C. R., Neel, B. G., Kahn, B. B. (2007). Protein-tyrosine Phosphatase 1B Deficiency Reduces Insulin Resistance and the Diabetic Phenotype in Mice with Polygenic Insulin Resistance. J. Biol. Chem. 282: 23829-23840 [Abstract] [Full Text]  
  • Bunce, M. W., Gonzales, M. L., Anderson, R. A. (2006). Stress-ING Out: Phosphoinositides Mediate the Cellular Stress Response. Sci Signal 2006: pe46-pe46 [Abstract] [Full Text]  
  • Draznin, B. (2006). Molecular Mechanisms of Insulin Resistance: Serine Phosphorylation of Insulin Receptor Substrate-1 and Increased Expression of p85{alpha}: The Two Sides of a Coin.. Diabetes 55: 2392-2397 [Abstract] [Full Text]  
  • Barbour, L. A., Mizanoor Rahman, S., Gurevich, I., Leitner, J. W., Fischer, S. J., Roper, M. D., Knotts, T. A., Vo, Y., McCurdy, C. E., Yakar, S., LeRoith, D., Kahn, C. R., Cantley, L. C., Friedman, J. E., Draznin, B. (2005). Increased P85{alpha} Is a Potent Negative Regulator of Skeletal Muscle Insulin Signaling and Induces in Vivo Insulin Resistance Associated with Growth Hormone Excess. J. Biol. Chem. 280: 37489-37494 [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»