CELL BIOLOGY AND METABOLISM
Regulation of GLUT1 Gene Transcription by the Serine/Threonine Kinase Akt1*

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We used mouse hepatoma (Hepa1c1c7) cells to study the role of the serine/threonine kinase Akt in the induction ofGLUT1 gene expression. In order to selectively turn on the Akt kinase cascade, we expressed a hydroxytamoxifen-regulatable form of Akt (myristoylated Akt1 estrogen receptor chimera (MER-Akt1)) in the Hepa1c1c7 cells; we verified that hydroxytamoxifen stimulates MER-Akt1 activity to a similar extent as the activation of endogenous Akt by insulin. Our studies reveal that stimulation of MER-Akt1 by hydroxytamoxifen induces GLUT1 mRNA and protein accumulation to levels comparable to that induced by insulin; therefore, activation of the Akt cascade suffices to induce GLUT1 gene expression in this cell system. Furthermore, expression of a kinase-inactive Akt mutant partially inhibits the response of the GLUT1 gene to insulin. Additional studies reveal that the induction of GLUT1 mRNA by Akt and by insulin reflects increased mRNA synthesis and not decreased mRNA degradation. Our findings imply that theGLUT1 gene responds to insulin at the transcriptional level and that Akt mediates a step in the activation of GLUT1gene expression in this system.

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This work was supported in part by National Institutes of Health Grants DK 34926 (to R. A. R.) and ES08655 (to J. P. W.), an American Diabetes Association Mentor-Based Postdoctoral Fellowship (to K. N.), and a Feodor-Lynen Fellowship of the Alexander von Humboldt-Stiftung (to A. B.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

© 1999 ASBMB. Currently published by Elsevier Inc; originally published by American Society for Biochemistry and Molecular Biology.