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

Abstract

FB, Davis PJ. Thyroid hormone inhibition in L6 myoblasts of IGF-Imediated glucose uptake and proliferation: new roles for integrin ␣v␤3. Am J Physiol Cell Physiol 307: C150-C161, 2014. First published May 7, 2014 doi:10.1152/ajpcell.00308.2013.-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 ␣v␤3. 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 ␣v␤3-mediated modulatory actions of T4 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 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-GlyAsp (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 ␣v␤3, 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. glucose transport; insulin-like growth factor type I; fluorescenceactivated cell sorting; tetraiodothyroacetic acid; thyroxine; triiodothyronine; mitogen-activated protein kinase; extracellular regulated kinase 1/2; phosphatidylinositol 3-kinase

Tetrac as an anti-angiogenic agent in cancer

“…In a wound-healing assay, tetrac did not influence basal cell migration, but did inhibit enhanced migration by VEGF (Balzan et al 2013). Tetrac has further been shown to block the pro-angiogenic activities of EGFR and PDGFR, and is hypothesised to inhibit the actions of the insulinlike growth factor 1 receptor (Davis et al 2013c, Incerpi et al 2014.…”

Maternal Thyroid Dysfunctions and Neonatal Bone Maldevelopment

“…Thyroid hormones (THs) play an essential role during the fetal and neonatal development (Gereben et al, 2008;Namba et al, 2008;El-bakry et al, 2010;Ahmed, 2011Ahmed, , 2012aAhmed, ,b, 2013Ahmed, , 2014Ahmed, , 2015aAhmed, -c, 2016aAhmed, -d, 2017aAhmed, -v, 2018aAhmed et al, 2008Ahmed et al, , 2010Ahmed et al, , 2013aAhmed et al, ,b, 2014Ahmed et al, , 2015aAhmed et al, ,b, 2018Ahmed and Incerpi, 2013;Van Hercket al, 2013;Ahmed andEl-Gareib, 2014,Incerpi et al, 2014Candelotti et al, 2015;De Vito et al, 2015;El-Ghareeb et al, 2016;Ahmed and El-Gareib, 2017), particularlythe normal growth of bone cells (Kvistad et al, 2004). THs also induce the cellular proliferation of cartilage growth in the epiphyseal plate of long bones by stimulation the release of growth hormone (GH) (Kvistad et al, 2004;Sbaihi et al, 2007) and IGF(insulin-growth factor) (Awad, 2002;El-bakry et al, 2010).In addition, thyroid receptors (TRs; α and β) were found in chondrocytes, growth plat, and osteoblasts (Bradley et al, 1992;Ballock et al, 1999;Siddiqi et al, 2002;Bassett and Williams, 2003).…”

Maternal Hypothyroidism-Milk Ejections: What is the Link?

“…The normal activity for the maternal hypothalamic-pituitary-thyroid axis (HPTA) isdynamic for the developing fetuses and neonates (Ahmed, 2011(Ahmed, , 2012a(Ahmed, ,b, 2013(Ahmed, , 2014(Ahmed, , 2015a From the previous data, I hypothesized that the maternal THs play active roles in the lactation process. The maternal hypothyroidism may directly or indirectly increase the risk of the premature mammary involution and destruction of the mammary tissue.…”