3,5,3' Triiodo-L-thyronine (T3) 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 T(3), 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 T3 resulted in a 200%-300% stimulation of PI-3k, as measured by the production of labeled (32)P-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