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
  • AJP Cell Physiology, July 2014, American Physiological Society
  • DOI: 10.1152/ajpcell.00308.2013

THs, integrin, IGF, L6 myoblasts

What is it about?

Thyroid hormones L-thyroxine (T4) and 3,3=,5-triiodo-L-thyronine (T3) have been shown to initiate shortand long-term effects via a plasma membrane receptor site located on integrin v3. 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 T4 and IGF-I in rat L6 myoblasts, we have examined integrin v3-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-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 T4 caused little or no cell proliferation but prevented both glucose uptake and proliferative actions of IGF-I. These actions of T4 were mediated by an Arg-Gly- Asp (RGD)-sensitive pathway, suggesting the existence of crosstalk between IGFIR 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-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 T4 that modified the effects of IGF-I. We conclude that thyroid hormone inhibits IGF-I-stimulated glucose uptake and cell proliferation in L6 myoblasts.

Why is it important?

We conclude that thyroid hormone inhibits IGF-I-stimulated glucose uptake and cell proliferation in L6 myoblasts.


Ahmed R. G. (Author)
Division of Anatomy and Embryology, Zoology department, Faculty of Science, Beni-Suef University, Egypt.

Glucose intolerance is common in hyperthyroidism. Decreased peripheral insulin sensitivity with impaired insulin secretion are factors contributing to the development of abnormal glucose tolerance in the hyperthyroid state (31, 67). However, the mechanisms involved in this action of thyroid hormone are incompletely understood (54). An insight provided by the current studies is that thyroid hormone impairs glucose uptake in L6 myoblasts that is promoted by IGF-I, functionally giving rise to IGF-I resistance that can be considered as a part of a differentiation process involving L6 cells. One approach to interpretation of these results is that impairment by thyroid hormone of IGF-I-stimulated glucose uptake in L6 myoblasts is antianabolic and might contribute to differentiation of these cells.

The following have contributed to this page: Ahmed R. G.