3,5,3′ Triiodo-L-thyronine stimulates 2-deoxy-D-glucose transport into L6 muscle cells through the phosphorylation of insulin receptor β and the activation of PI-3k

3,5,3' Triiodo-L-thyronine (T-3) stimulated the uptake of 2-deoxy-D-glucose (2-DOG) into L6 cells, nongenomically, starting at subpicomolar concentrations and reaching a peak at concentrations of 1-10 nM. Stimulation at the peak was usually approximately 250%. The uptake of 2-DOG declined with higher concentrations of T-3. The dose-response curve of insulin is similar in shape to that of T3, and its peak stimulation can even reach 600% over the control. Wortmannin, an inhibitor of the PI-3k, completely inhibited the stimulation of 2-DOG uptake by T-3, with no effect on the control cells. L6 cells exposed for 10 minutes to T-3 resulted in a 200%-300% stimulation of PI-3k, as measured by the production of labeled P-32-PI-3P. Similar results were obtained with insulin. After incubation for 5 minutes with L6 cells, T-3 increased phosphorylation of the insulin receptor beta subunit; this correlated significantly with the degree of stimulation of 2-DOG uptake at 90 minutes (r = 0.89, p <= 0.01). These findings suggest that T-3 stimulates the uptake of 2-DOG into L6 muscle cells, in a manner similar to that of insulin.