In:
American Journal of Physiology-Cell Physiology, American Physiological Society, Vol. 307, No. 2 ( 2014-07-15), p. C150-C161
Abstract:
Thyroid hormones l-thyroxine (T 4 ) and 3,3′,5-triiodo-l-thyronine (T 3 ) 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 T 4 and IGF-I in rat L6 myoblasts, we have examined integrin αvβ3-mediated modulatory actions of T 4 on glucose uptake, measured through carrier-mediated 2-deoxy-[ 3 H]-d-glucose uptake, and on cell proliferation stimulated by IGF-I, assessed by cell counting, [ 3 H]-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 T 4 caused little or no cell proliferation but prevented both glucose uptake and proliferative actions of IGF-I. These actions of T 4 were mediated by an Arg-Gly-Asp (RGD)-sensitive pathway, suggesting the existence of crosstalk between IGFIR and the T 4 receptor located near the RGD recognition site on the integrin. An RGD-sequence-containing integrin inhibitor, a monoclonal antibody to αvβ3, and the T 4 metabolite tetraiodothyroacetic acid all blocked the inhibition by T 4 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 T 4 that modified the effects of IGF-I. We conclude that thyroid hormone inhibits IGF-I-stimulated glucose uptake and cell proliferation in L6 myoblasts.
Type of Medium:
Online Resource
ISSN:
0363-6143
,
1522-1563
DOI:
10.1152/ajpcell.00308.2013
Language:
English
Publisher:
American Physiological Society
Publication Date:
2014
detail.hit.zdb_id:
1477334-X
SSG:
12
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