This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart 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 Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Huang, D. Articles by Bryer-Ash, M. Search for Related Content PubMed PubMed Citation Articles by Huang, D. Articles by Bryer-Ash, M.

Reduced Expression of Focal Adhesion Kinase Disrupts Insulin Action in Skeletal Muscle Cells

West Los Angeles Veterans Administration Medical Center and UCLA Gonda (Goldschmied) Diabetes Center (D.H., M.K., M.B.), Division of Endocrinology, Diabetes and Hypertension, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, California 90095; and Department of Stomatology and Anatomy (D.I.), University of California, San Francisco, California 94143

Address all correspondence and requests for reprints to: Michael Bryer-Ash, M.D., UCLA Division of Endocrinology, Diabetes and Hypertension; 900 Veteran Avenue, Warren Hall Room 24-130; Los Angeles, California 90095. E-mail: mbryerash{at}mednet.ucla.edu.

Integrins mediate interactions between cells and extracellular matrix proteins that modulate growth factor signaling. Focal adhesion kinase (FAK) is a key multifunctional integrin pathway protein. We recently reported that disruption of FAK impairs insulin-mediated glycogen synthesis in hepatocytes. To test the hypothesis that FAK regulates skeletal muscle insulin action, we reduced FAK expression in L6 myotubes using FAK antisense. In untransfected myotubes, insulin stimulated both FAK tyrosine phosphorylation and kinase activity. Cells treated with antisense FAK showed 78 and 53% reductions in FAK mRNA and FAK protein, respectively, whereas insulin receptor substrate 1/2 and paxillin abundance were unaffected. Insulin-stimulated U-¹⁴C-glucose incorporation into glycogen was abolished by FAK antisense, and 2-deoxy-glucose uptake and glucose transporter 4 (GLUT4) translocation were both markedly attenuated. Antisense FAK did not alter GLUT1 or GLUT3 protein abundance. Immunofluorescence staining showed decreased FAK Tyr³⁹⁷ phosphorylation and reduced actin stress fibers. Thus, in skeletal myotubes, FAK regulates the insulin-mediated cytoskeletal rearrangement essential for normal glucose transport and glycogen synthesis. Integrin signaling may play an important regulatory role in muscle insulin action.

This article has been cited by other articles:

				B. Bisht, K. Srinivasan, and C. S. Dey In vivo inhibition of focal adhesion kinase causes insulin resistance J. Physiol., August 15, 2008; 586(16): 3825 - 3837. [Abstract] [Full Text] [PDF]

				F. Frasca, G. Pandini, R. Malaguarnera, A. Mandarino, R. L. Messina, L. Sciacca, A. Belfiore, and R. Vigneri Role of c-Abl in Directing Metabolic versus Mitogenic Effects in Insulin Receptor Signaling J. Biol. Chem., September 7, 2007; 282(36): 26077 - 26088. [Abstract] [Full Text] [PDF]

				D. Huang, M. Khoe, M. Befekadu, S. Chung, Y. Takata, D. Ilic, and M. Bryer-Ash Focal adhesion kinase mediates cell survival via NF-{kappa}B and ERK signaling pathways Am J Physiol Cell Physiol, April 1, 2007; 292(4): C1339 - C1352. [Abstract] [Full Text] [PDF]