Triiodothyronine stimulates and glucagon inhibits transcription of the acetyl-CoA carboxylase gene in chick embryo hepatocytes: glucose and insulin amplify the effect of triiodothyronine.
The mechanisms by which triiodothyronine (T3), glucose, insulin, and glucagon regulate acetyl-CoA carboxylase expression in primary cultures of chick embryo hepatocytes have been investigated. Incubating hepatocytes with T3 in the absence of glucose caused a fourfold increase in acetyl-CoA carboxylase activity. Addition of glucose (20 mM) enhanced the T3-induced increase in acetyl-CoA carboxylase activity by threefold but had no effect on enzyme activity in the absence of T3. The effects of T3 and glucose on acetyl-CoA carboxylase activity were accompanied by similar changes in acetyl-CoA carboxylase mRNA levels, indicating that regulation occurred at a pretranslational step. Xylitol mimicked the effect of glucose on acetyl-CoA carboxylase mRNA abundance, suggesting that an intermediate(s) of the nonoxidative branch of the pentose phosphate pathway may be involved in mediating this response. Insulin accelerated the accumulation of acetyl-CoA carboxylase mRNA abundance caused by T3 and glucose but had no effect on steady-state levels of acetyl-CoA carboxylase mRNA in the absence or presence of T3. Glucagon caused a 65% decrease in the accumulation of acetyl-CoA carboxylase mRNA in hepatocytes incubated with T3 and glucose. The effects of T3, glucose, insulin, and glucagon on the abundance of acetyl-CoA carboxylase mRNA were accounted for by changes in the transcription rate of the acetyl-CoA carboxylase gene. These data support the hypothesis that T3, glucose, insulin, and glucagon play a role in mediating the effects of nutritional manipulation on transcription of acetyl-CoA carboxylase in liver.
Hillgartner
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FB
Department of Biochemistry, School of Medicine, West Virginia University, Morgantown 26506, USA. fbhill@wvnvms.wvnet.edu
Charron
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T
Chesnut
K A
KA
D000103:Acetyl-CoA Carboxylase / Q000235:genetics*; D000818:Animals; D002478:Cells, Cultured; D002642:Chick Embryo; D015971:Gene Expression Regulation, Enzymologic; D005934:Glucagon / Q000494:pharmacology*; D005947:Glucose / Q000494:pharmacology; D019298:Glucose-6-Phosphate / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology; D008099:Liver / Q000166:cytology / Q000196:embryology* / Q000201:enzymology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects*; D014284:Triiodothyronine / Q000494:pharmacology*; D014993:Xylitol / Q000378:metabolism / Q000494:pharmacology
D007328:Insulin; D012333:RNA, Messenger; D014284:Triiodothyronine; D019298:Glucose-6-Phosphate; D005934:Glucagon; D000103:Acetyl-CoA Carboxylase; D005947:Glucose; D014993:Xylitol