Regulation of the expression of the L-type pyruvate kinase gene in adult rat hepatocytes in primary culture.
Hepatocytes isolated from adult fasted rats and cultured in the presence of thyroid hormones, glucocorticoids, and in a serum-free medium conserve the essentials of their differentiated function and hormonal sensitivity for at least 1 week. In these cells, the gene for L-type pyruvate kinase is expressed only when glucose and insulin are present together, each of them being inactive by itself. Inhibition of the expression of the L-type pyruvate kinase gene which occurs when glucose and/or insulin are removed from the culture medium is not associated with accumulation of the phosphoenolpyruvate carboxykinase mRNA, which argues against the involvement of intracellular cyclic AMP in this phenomenon. Rather, a transcriptional activator, derived from carbohydrate metabolism and accumulating in the presence of insulin, seems to be needed to support the expression of the L-type pyruvate kinase gene. Glucagon, in vitro as in vivo, inhibits production of the L-type pyruvate kinase mRNAs. In addition to their roles on the production of these mRNAs, glucose and insulin on the one hand and glucagon on the other have profound effects on the stability of the L-type pyruvate kinase messengers: the half-life of the mRNA whose production has been blocked by actinomycin D is 1 h in the presence of glucagon and 24 h in the presence of glucose and insulin. Glucagon and glucose/insulin partially antagonize each other's effect on mRNA stability.
Decaux
J F
JF
Institut National de la Santé et de la Recherche Médicale, U 129, Paris, France.
Antoine
B
B
Kahn
A
A
D000818:Animals; D015152:Blotting, Northern; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D005786:Gene Expression Regulation; D005934:Glucagon / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology; D006728:Hormones / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000235:genetics; D007700:Kinetics; D008099:Liver / Q000166:cytology / Q000201:enzymology*; D011770:Pyruvate Kinase / Q000037:antagonists & inhibitors / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats
D006728:Hormones; D007328:Insulin; D007527:Isoenzymes; D012333:RNA, Messenger; D003609:Dactinomycin; D005576:Colforsin; D005934:Glucagon; D000242:Cyclic AMP; D011770:Pyruvate Kinase; D005947:Glucose