Thyroid hormones L-thyroxine (T4) and 3,5,3’-triiodo-L-thyronine (T3) have been shown to initiate short- and long-term effects via a plasma membrane receptor site located on integrin vβ3. Also insulin-like growth factor-1 (IGF-1) activity is known to be subject to regulation by this integrin. To investigate the possible cross-talk between T4 and IGF-1 in rat L6 myoblasts, we have examined integrin αvβ3-mediated modulatory actions of T4 on glucose uptake, measured through carrier-mediated 2-deoxy-[3H]-D-glucose uptake, and on cell proliferation stimulated by IGF-1, assessed by cell counting, [3H]-thymidine incorporation and FACS analysis. IGF-1 stimulated glucose transport and cell proliferation via the cell surface IGF-1 receptor (IGF1R) and, downstream of the receptor, by the phosphatidylinositol 3-kinase signal transduction pathway. Addition of 0.1 nM free T4 caused little or no cell proliferation, but prevented both glucose uptake and proliferative actions of IGF1. These actions of T4 were mediated by an Arg-Gly-Asp (RGD)-sensitive pathway, suggesting the existence of crosstalk between IGF1R and the T4 receptor located near the RGD recognition site on the integrin. An RGD-sequence-containing integrin inhibitor, a monoclonal antibody to v3, and the T4 metabolite tetraiodothyroacetic acid all blocked the inhibition by T4 of IGF-1-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-1, and also showed a role for ERK1/2 in the actions of T4 that modified the effects of IGF-1. We conclude that thyroid hormone inhibits IGF-1-stimulated glucose uptake and cell proliferation in L6 myoblasts.
Incerpi, S., Hsieh, M.T., Lin, H.Y., Cheng, G.Y., De Vito, P., Fiore, A.M., et al. (2014). Thyroid hormone inhibition in L6 myoblasts of IGF-1-mediated glucose uptake and proliferation: new roles for integrin αvβ3. AMERICAN JOURNAL OF PHYSIOLOGY, 307(2), C150-C161 [10.1152/ajpcell.00308.2013].