Effect of thyroid hormones on oxidative and nonoxidative glucose metabolism in humans

The glucoregulatory function of thyroid hormones was investigated in six healthy subjects before and after 14 day 3,5,3',5'-tetraiodothyronine (T4) treatment (300 micrograms/day) using a sequential clamp protocol for 5 h at euglycemia (0-2 h) and hyperglycemia (165 mg/dl, 2-5 h) and different insulin infusion rates (1.0 for 0-3.5 h and 6.5 mU.kg-1.min-1, for 3.5-5 h). T4 treatment increased basal energy expenditure (+8%), glucose disposal (+31%), and oxidation (+87%) but decreased nonoxidative glucose metabolism (-30%) and was without effect on lipid oxidation. During the euglycemic clamp, T4 treatment enhanced insulin-induced glucose disposal (+16%), glucose oxidation (+34%), and inhibition of lipid oxidation (-66 vs. -40%); nonoxidative glucose metabolism was stimulated to a similar extent before and after T4. During hyperglycemia, 3,5,3'-triiodothyronine (T3) did not affect glucose disposal but increased carbohydrate-induced lipogenesis at both insulin infusion rates. We conclude that T4 treatment promotes glucose disposal and oxidation, T3 decreases noninsulin-mediated glucose storage but does not antagonize insulin action.