Differential regulation of glucose transporter isoforms by thyroid hormone in rat heart

Since thyroid hormone stimulates cardiac metabolism, for which glucose is an important fuel, we examined the effects of thyroid hormone on glucose transporter gene expression in rat heart. Treatment of hypothyroid animals with T3 for up to 6 days caused a 2-fold increase in GLUT4 mRNA at 1 day, and a 4-fold increase at 6 days (per unit DNA). GLUT4 protein, however, was not increased. In contrast, GLUT1 mRNA was transiently decreased by T3 treatment at 1 and 3 days, but returned to normal by 6 days. Concomitantly, GLUT1 protein decreased to 18% of the control value at 6 days. In chronically hypothyroid or hyperthyroid rats, GLUT4 mRNA varied directly with thyroid status, but GLUT4 protein was invariant, consistent with the acute effects of T3 treatment. Moreover, hypothyroidism increased GLUT1 mRNA and protein expression. We conclude that, in contrast to previous observations in skeletal muscle, GLUT4 protein content in rat heart is not altered by thyroid hormone. Cardiac GLUT1 expression is increased in hypothyroidism, and suppressed by thyroid hormone, at both the protein and mRNA levels. The observed discrepancy between GLUT4 mRNA and protein levels suggests that post-transcriptional regulatory events play a major role in GLUT4 expression in rat heart.