Thyroid Hormone Increases Muscle/Fat Glucose Transporter Gene Expression in Rat Skeletal Muscle*

Abstract

The enhancement of metabolic rate by thyroid hormone in target tissues is accompanied by increased glucose utilization, which in skeletal muscle and many other tissues is regulated at the level of membrane transport. To elucidate the role of thyroid hormone as a regulator of glucose transport in skeletal muscle, we have examined its effects on the expression of the muscle/fat (insulin-regulatable) glucose transporter, a distinct glucose transporter isotype whose expression is limited to insulin-sensitive tissues and which appears to be the major glucose transport protein in skeletal muscle. Treatment of hypothyroid rats with L-T3 (T3; 100 micrograms/100 g BW.day for 6 days) increased the abundance of the muscle/fat glucose transporter protein in crude membranes from hindlimb muscle, assessed by immunoblotting, to 145 +/- 8% of the control value in animals fasted for 17-20 h before death and to 159 +/- 16% of the control value in animals fed ad libitum (mean +/- SE). In purified plasma membranes, this effect of thyroid hormone was greater (208 +/- 23% and 219 +/- 13% of control in fasted and fed animals, respectively). Similar increases were found in an intracellular membrane fraction. Levels of muscle/fat glucose transporter mRNA were also increased in hindlimb muscle from the T3-treated rats, to 261 +/- 17% and 316 +/- 23% of control values in fasted and fed animals, respectively. In contrast, the erythroid glucose transporter protein and its mRNA, which are only weakly expressed in skeletal muscle but strongly expressed in brain, were not substantially increased by T3 treatment in either tissue. In experiments comparing hypothyroid, euthyroid, and chronically T4-treated animals, muscle/fat glucose transporter protein and mRNA abundance in skeletal muscle were also found to be dependent on thyroid status. Thyroid hormone may, thus, be an important regulator of the muscle/fat glucose transporter in skeletal muscle.