Insulin and cyclic AMP act at different levels on transcription of the L-type pyruvate kinase gene.
We previously demonstrated that, in hepatocytes in primary culture, the role of insulin on induction of L-type pyruvate kinase (L-PK) gene expression was mainly to induce glucokinase synthesis, needed for glucose phosphorylation to glucose 6-phosphate. However, we show here that when hepatocytes have been isolated from rats starved for 72 h, glucose and constitutive glucokinase expression was not sufficient to fully stimulate the L-PK promoter, low insulin concentrations being still required. In addition, activation remains sensitive to cAMP inhibition, but cannot be reproduced in the absence of insulin by a competitive cAMP antagonist. We propose that both insulin and cAMP act on expression of the L-PK gene at, at least, two levels: positive and negative regulation of glucokinase gene expression, and more downstream levels.
Cuif
M H
MH
Institut Cochin de Génétique Moléculaire, U. 129 INSERM, Université René Descartes, Paris, France.
Doiron
B
B
Kahn
A
A
D000818:Animals; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism* / Q000494:pharmacology; D005786:Gene Expression Regulation; D005941:Glucokinase / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000378:metabolism* / Q000494:pharmacology; D008099:Liver / Q000166:cytology; D008297:Male; D011401:Promoter Regions, Genetic; D011770:Pyruvate Kinase / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014158:Transcription, Genetic; D015533:Transcriptional Activation
D007328:Insulin; D000242:Cyclic AMP; D005941:Glucokinase; D011770:Pyruvate Kinase; D005947:Glucose