3,5,3' Triiodo-L-thyronine stimulates 2-deoxy-D-glucose transport into L6 muscle cells through the phosphorylation of insulin receptor beta and the activation of PI-3k.
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 <or= 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.
Gordon
Amirav
A
Hebrew University, Hadassah Medical School, Experimental Medicine & Cancer Research, Jerusalem, Israel. amirav@md.huji.ac.il
Swartz
Harry
H
Shwartz
Henia
H
D000818:Animals; D001692:Biological Transport; D049109:Cell Proliferation; D003847:Deoxyglucose / Q000378:metabolism*; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism; D018482:Muscle, Skeletal / Q000166:cytology* / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats; D011972:Receptor, Insulin / Q000378:metabolism*; D013997:Time Factors; D014285:Triiodothyronine, Reverse / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D007328:Insulin; D014285:Triiodothyronine, Reverse; D003847:Deoxyglucose; D019869:Phosphatidylinositol 3-Kinases; D011972:Receptor, Insulin