A rapid, extranuclear effect of 3,5,3'-triiodothyronine on sugar uptake by several tissues in the rat in vivo. Evidence for a physiological role for the thyroid hormone action at the level of the plasma membrane.
T3 produced a prompt and biphasic change in the uptake of 2-deoxy-D-glucose (dGlc) by atria, ventricles, diaphragm, and fat in the rat in vivo. At the lower physiological doses T3 produced a dose-related increase in tissue dGlc uptake; the lowest effective concentration was 5-10 ng/100 g BW, and maximal effect of about 75-100% increase above control values was seen at a T3 dose of 25 (diaphragm) or 100 ng. At pharmacological doses of 5 and 50 micrograms/100 g BW T3 inhibited dGlc uptake by about 50%. Evaluation of the physiological related stimulatory effect of T3 on dGlc uptake in the four tissues revealed that it was independent of new protein synthesis, because it was not inhibited by cycloheximide which blocked [3H]leucine incorporation by more than 95%, and that it was thyroid hormone specific, as judged from the order of potency of several T3 analogs: 3'-isopropyl-L-T2 greater than or equal to L-T3 greater than L-T4 = D-T3 greater than D-T4; L-rT3, 3,5-L-T2, and DL-thyronine were without effect. Additional studies demonstrated that in the four tissues employed T3 acted to promote sugar uptake by increasing the activity of the sugar transport system located at the plasma membrane. The present study together with previous in vitro and in vivo studies, in the same and other tissues, provide a strong evidence in support of a physiological role for the action of thyroid hormone at the level of the plasma membrane to increase cellular sugar uptake.
Segal
J
J
Hubert H. Humphrey Center for Experimental Medicine and Cancer Research, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism*; D003513:Cycloheximide / Q000494:pharmacology; D003837:Deoxy Sugars / Q000378:metabolism*; D003847:Deoxyglucose / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D007328:Insulin / Q000097:blood; D007700:Kinetics; D008297:Male; D009132:Muscles / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D009928:Organ Specificity; D010766:Phosphorylation; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D013974:Thyroxine / Q000097:blood; D014284:Triiodothyronine / Q000031:analogs & derivatives / Q000097:blood / Q000494:pharmacology* / Q000502:physiology
D003837:Deoxy Sugars; D007328:Insulin; D014284:Triiodothyronine; D003513:Cycloheximide; D003847:Deoxyglucose; D005947:Glucose; D013974:Thyroxine