Sp. Weinstein et Rs. Haber, GLUCOSE-TRANSPORT STIMULATION BY THYROID-HORMONE IN ARL 15 CELLS - PARTIAL ROLE OF INCREASED GLUT-1 GLUCOSE-TRANSPORTER GENE-TRANSCRIPTION, Thyroid, 3(2), 1993, pp. 135-142
We have previously reported that the stimulation of glucose transport
by thyroid hormone in the rat liver-derived ARL 15 cell line is attrib
utable, at least in part, to increased abundance of cellular glucose t
ransporters with a corresponding increase in the mRNA coding for the G
LUT1 glucose transporter isoform. To elucidate further the mechanism b
y which thyroid hormone increases glucose transport, we examined the t
ime-course of the effect of L-triiodothyronine (T3) on H-3-2-deoxygluc
ose uptake, GLUT1 protein abundance, and GLUT1 mRNA abundance in ARL 1
5 cells. At 6 h of T3 treatment, H-3-2-deoxyglucose uptake was increas
ed by 40 +/- 11%, whereas the abundance of GLUT1 protein in cell extra
cts had not yet changed at this time. At 48 h, GLUT1 protein was incre
ased by 58 +/- 10%, whereas H-3-2-deoxyglucose uptake at this time was
increased by 116 +/- 14%. GLUT1 mRNA levels rose within 4 h of T3 tre
atment, preceding the increase in GLUT1 protein, and more than doubled
by 24 h. In additional experiments to determine the mechanism by whic
h T3 increases GLUT1 mRNA, T3 treatment for 48 h increased the rate of
transcription of the GLUT1 gene, determined by nuclear run-on analysi
s, by 55 +/- 11%. T3 treatment did not significantly alter the half-li
fe 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 induc
tion of this mRNA by T3 in the presence of these inhibitors. We conclu
de that thyroid hormone regulates glucose transport in ARL 15 cells, i
n part, by increasing GLUT1 glucose transporter gene transcription. Wh
ether this effect is due to a direct interaction of T3 nuclear recepto
rs with specific DNA sequences in the GLUT1 gene is not clear at prese
nt. Since the T3-induced increase in GLUT1 protein could not fully acc
ount for the degree of stimulation of hexose uptake, thyroid hormone m
ay additionally activate pre-existing GLUT1 glucose transporters.