Acute effect of thyroid hormone on the heart: An extranuclear increase in sugar uptake

Abstract

The thyroid hromone 3,5,3′-triiodo-L-thyronine (T3) produced a rapid increase in [ 3H]2-deoxyglucose (2-DG) uptake by freshly isolated rat heart slices in vitro, an effect that was evident after 1 min of pre-incubation with the hormone. This stimulatory effect of T3 was dose-related: the lowest effective concentration was 1 p m and maximal effect of about 80% above control was seen at 1 n m. Studies with several thyroid hormone analogues revealed that l-T3 was the most effective analogue which was followed in a decreasing order of potency by l-T4 = d-T3 > d-T4 > 3,5- l-T2 > rT3 > dL-thyronine. Further, the T3-induced increase in 2-DG uptake was independent of new protein synthesis because it was not blocked by the protein synthesis inhibitor cycloheximide under conditions in which [ 3H] leucine incorporation was inhibited by approximately 95%. Evaluation of the mechanism through which T3 exerts this action revealed that the uptake of 2-DG and 3-0-methyl- d-glucose (30MG) by heart slices was saturable, but that of l-glucose was not, and that T3 produced a similar increase in the uptake of both 2-DG and 30MG but failed to change l-glucose uptake. Saturation curve analysis of 2-DG and 30 MG uptake revealed that T3 increased V max values but had no effect on K m values. Moreover, T3, which promoted total 2-DG uptake rate, had no effect on the proportionate phosphorylation rate of 2-DG to 2-DG-6-phosphate by hexokinase. From this study it is concluded that thyroid hormone produces a direct and acute effect on the heart. This prompt effect of T3 to increase sugar uptake by heart slices, owing to the increase in the V max of the sugar transport system, is extranuclear in nature, is thyroid hormone specific, and has a physiologic relevance.