Transcriptional and post-transcriptional regulation of L-type pyruvate kinase in diabetic rat liver by insulin and dietary fructose.
Regulation of the expression of the hepatic L-type pyruvate kinase gene by insulin and dietary fructose was studied in diabetic rats. Insulin increased the levels of putative nuclear RNA precursor species of this enzyme in parallel with that of total cellular pyruvate kinase L mRNA. These changes occurred more slowly than those induced by dietary fructose. Insulin caused a 3-fold increase in transcription of the pyruvate kinase L gene after 6 h and a 6-fold increase after 16 h. The increase caused by insulin was inhibited by glucagon, but not by adrenalectomy. Cycloheximide inhibited the induction caused by insulin, suggesting that insulin may stimulate transcription of the pyruvate kinase L gene by stimulating synthesis of some unknown protein. On the other hand, feeding fructose had no effect on transcription of the pyruvate kinase L gene. We previously showed that increases in the levels of putative nuclear RNA precursor species of the pyruvate kinase L after fructose feeding preceded changes in the levels of cytosolic pyruvate kinase L mRNA (Inoue, H., Noguchi, T., and Tanaka, T. (1984) J. Biochem. (Tokyo) 96, 1457-1462). Thus, dietary fructose may increase the levels of pyruvate kinase L mRNA by stabilizing nuclear RNA species. Glucagon inhibited the increase in pyruvate kinase L mRNA caused by dietary fructose. However, plasma levels of glucagon and thyroid hormones were not decreased in diabetic rats after fructose feeding. In addition, treatment with triiodo-L-thyronine caused no change in the pyruvate kinase L mRNA level. Furthermore, adrenalectomy did not impair enzyme induction by fructose in diabetic rats. Thus, the effect of fructose on pyruvate kinase L seems to be directly on the liver.
Noguchi
T
T
Inoue
H
H
Tanaka
T
T
D000315:Adrenalectomy; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology; D003600:Cytosol / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology*; D005632:Fructose / Q000494:pharmacology*; D005934:Glucagon / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D011770:Pyruvate Kinase / Q000235:genetics*; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D014158:Transcription, Genetic / Q000187:drug effects*; D014284:Triiodothyronine / Q000494:pharmacology
D007328:Insulin; D012333:RNA, Messenger; D014284:Triiodothyronine; D005632:Fructose; D012313:RNA; D005934:Glucagon; D003513:Cycloheximide; D011770:Pyruvate Kinase