Aim: 

Thyroid hormone through its membrane receptor, the integrin aVb3, has been reported to be able to modulate the activity of growth factors. We studied glucose uptake in L-6 myoblasts in order to determine whether thyroid hormone modulates the activity of IGF-1, perhaps through crosstalk between the integrin and IGF-1R.

Methods: 

The carrier-mediated hexose uptake (cytochalasin B-inhibitable) was measured for 10 min at 37°C in Hepes-Buffered Saline by 10 mM 2-deoxy-[³H]-D-glucose, after 4 hours of serum depletion.

Results: 

IGF-1 activated glucose uptake in L-6 cells by a PI 3-K-dependent, that is, wortmannin-sensitive, mechanism. Thyroid hormones, 3,5,3'-triiodo-L-thyronine (T3; 1 nM) and L-thyroxine (T4; 100 nM) both stimulated glucose uptake. In the presence of IGF-1, however, T3 and T4 inhibited the IGF-1 effect on glucose uptake by a pathway that was RGD-sensitive, suggesting the involvement of the cell surface receptor for thyroid hormone at the RGD (Arg-Gly-Asp) recognition site on integrin alphaVbeta3 in iodothyronine action on the effect of IGF-1. Echistatin, an RGD-sequence-containing inhibitor of integrins, blocked IGF-1 action on glucose uptake in L6 cells.

Conclusions: 

There are two modes of crosstalk between the integrin receptor for thyroid hormone on integrin alphaVbeta3 and the IGF-1 receptor. One level of crosstalk allows T3 and T4 to modulate IGF-1 action and requires PI 3-K activation. Another mode of crosstalk between the integrin and IGF-1R is thyroid hormone-independent and echistatin-sensitive.