Thyroid hormone inhibition in L6 myoblasts of IGF-I-mediated glucose uptake and proliferation: New roles for integrin αvβ3

Sandra Incerpi, Meng Ti Hsieh, Hung Yun Lin, Guei Yun Cheng, Paolo De Vito, Anna Maria Fiore, R. G. Ahmed, Rosanna Salvia, Elena Candelotti, Stefano Leone, Paolo Luly, Jens Z. Pedersen, Faith B. Davis, Paul J. Davis

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Abstract

Thyroid hormones L-thyroxine (T4) and 3,3′,5-triiodo-L-thyronine (Ser3) have been shown to initiate short- and long-term effects via a plasma membrane receptor site located on integrin αvβ3. Also insulin-like growth factor type I (IGF-I) activity is known to be subject to regulation by this integrin. To investigate the possible cross-talk between Ser4 and IGF-I in rat L6 myoblasts, we have examined integrin αvβ3-mediated modulatory actions of Ser4 on glucose uptake, measured through carrier-mediated 2-deoxy-[3H]-D-glucose uptake, and on cell proliferation stimulated by IGF-I, assessed by cell counting, [3H]-thymidine incorporation, and fluorescence-activated cell sorting analysis. IGF-I stimulated glucose transport and cell proliferation via the cell surface IGF-I receptor (IGFIR) and, downstream of the receptor, by the phosphatidylinositol 3-kinase signal transduction pathway. Addition of 0.1 nM free Ser4 caused little or no cell proliferation but prevented both glucose uptake and proliferative actions of IGF-I. These actions of Ser4 were mediated by an Arg-Gly-Asp (RGD)-sensitive pathway, suggesting the existence of crosstalk between IGFIR and the Ser4 receptor located near the RGD recognition site on the integrin. An RGD-sequence-containing integrin inhibitor, a monoclonal antibody to αvβ3, and the Ser4 metabolite tetraiodothyroacetic acid all blocked the inhibition by Ser4 of IGF-I-stimulated glucose uptake and cell proliferation. Western blotting confirmed roles for activated phosphatidylinositol 3-kinase and extracellular regulated kinase 1/2 (ERK1/2) in the effects of IGF-I and also showed a role for ERK1/2 in the actions of Ser4 that modified the effects of IGF-I. We conclude that thyroid hormone inhibits IGF-I-stimulated glucose uptake and cell proliferation in L6 myoblasts.

Original languageEnglish
JournalAmerican Journal of Physiology - Cell Physiology
Volume307
Issue number2
DOIs
Publication statusPublished - Jul 15 2014

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Keywords

  • Extracellular regulated kinase 1/2
  • Fluorescenceactivated cell sorting
  • Glucose transport
  • Insulin-like growth factor type I
  • Mitogen-activated protein kinase
  • Phosphatidylinositol 3-kinase
  • Tetraiodothyroacetic acid
  • Thyroxine
  • Triiodothyronine

ASJC Scopus subject areas

  • Cell Biology
  • Physiology

Cite this

Incerpi, S., Hsieh, M. T., Lin, H. Y., Cheng, G. Y., De Vito, P., Fiore, A. M., Ahmed, R. G., Salvia, R., Candelotti, E., Leone, S., Luly, P., Pedersen, J. Z., Davis, F. B., & Davis, P. J. (2014). Thyroid hormone inhibition in L6 myoblasts of IGF-I-mediated glucose uptake and proliferation: New roles for integrin αvβ3. American Journal of Physiology - Cell Physiology, 307(2). https://doi.org/10.1152/ajpcell.00308.2013