Glucose transport stimulation by thyroid hormone in ARL 15 cells: partial role of increased GLUT1 glucose transporter gene transcription.
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.(ABSTRACT TRUNCATED AT 250 WORDS)
Weinstein
S P
SP
Department of Medicine, Mount Sinai School of Medicine, New York, New York.
Haber
R S
RS
D000818:Animals; D001692:Biological Transport / Q000502:physiology; D002460:Cell Line; D004247:DNA / Q000032:analysis / Q000235:genetics; D003847:Deoxyglucose / Q000493:pharmacokinetics; D005796:Genes / Q000235:genetics*; D005947:Glucose / Q000493:pharmacokinetics*; D051272:Glucose Transporter Type 1; D006207:Half-Life; D015151:Immunoblotting; D007536:Isomerism; D008099:Liver / Q000166:cytology* / Q000378:metabolism / Q000502:physiology; D009004:Monosaccharide Transport Proteins / Q000032:analysis / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D051381:Rats; D013997:Time Factors; D014158:Transcription, Genetic; D014284:Triiodothyronine / Q000494:pharmacology*; D014316:Tritium
D051272:Glucose Transporter Type 1; D009004:Monosaccharide Transport Proteins; D012333:RNA, Messenger; C495679:Slc2a1 protein, rat; D014284:Triiodothyronine; D014316:Tritium; D004247:DNA; D003847:Deoxyglucose; D005947:Glucose