Glucose Transport Stimulation by Thyroid Hormone in ARL 15 Cells: Partial Role of Increased GLUT1 Glucose Transporter Gene Transcription

Abstract

We have previously reported that the stimulation of glucose transport by thyroid hormone in the rat liver-derived ARL 15 cell line is attributable, at least in part, to increased abundance of cellular glucose transporters with a corresponding increase in the mRNA coding for the GLUT1 glucose transporter isoform. To elucidate further the mechanism by which thyroid hormone increases glucose transport, we examined the time-course of the effect of L-triiodothyronine (T₃) on ³H-2-deoxyglucose uptake, GLUT1 protein abundance, and GLUT1 mRNA abundance in ARL 15 cells. At 6 h of T₃ treatment, ³H-2-deoxyglucose uptake was increased by 40 ± 11%, whereas the abundance of GLUT1 protein in cell extracts had not yet changed at this time. At 48 h, GLUT1 protein was increased by 58 ± 10%, whereas ³H-2-deoxyglucose uptake at this time was increased by 116 ± 14%. GLUT1 mRNA levels rose within 4 h of T₃ treatment, preceding the increase in GLUT1 protein, and more than doubled by 24 h. In additional experiments to determine the mechanism by which T₃ increases GLUT1 mRNA, T₃ treatment for 48 h increased the rate of transcription of the GLUT1 gene, determined by nuclear run-on analysis, by 55 ± 11%. T₃ treatment did not significantly alter the half-life of GLUT1 mRNA. In the presence of inhibitors of protein synthesis, GLUT1 mRNA increased at 6 h (5-7-fold), but there was no further induction of this mRNA by T₃ in the presence of these inhibitors.

We conclude that thyroid hormone regulates glucose transport in ARL 15 cells, in part, by increasing GLUT1 glucose transporter gene transcription. Whether this effect is due to a direct interaction of T₃ nuclear receptors with specific DNA sequences in the GLUT1 gene is not clear at present. Since the T₃-induced increase in GLUT1 protein could not fully account for the degree of stimulation of hexose uptake, thyroid hormone may additionally activate pre-existing GLUT1 glucose transporters.