Transcriptional glucose signaling through the glucose response element is mediated by the pentose phosphate pathway.
Glucose catabolism induces the expression of the L-type pyruvate kinase (L-PK) gene through the glucose response element (GIRE). The metabolic pathway used by glucose after its phosphorylation to glucose 6-phosphate by glucokinase to induce L-PK gene expression in hepatocytes remains unknown. The sugar alcohol xylitol is metabolized to xylulose 5-phosphate, an intermediate of the nonoxidative branch of the pentose phosphate pathway. In this study, we demonstrated that xylitol at low concentration (O.5 mM) induced the expression of the L-PK/CAT construct in glucose-responsive mhAT3F hepatoma cells at the same level as 20 mM glucose, while it did not affect intracellular concentration of glucose 6-phosphate significantly. The effect of xylitol on the induction of the L-PK gene expression was noncumulative with that of glucose since 20 mM glucose plus 5 mM xylitol induced the expression of the L-PK/CAT construct similarly to 20 mM glucose alone. In hepatocytes in primary culture, 5 mM xylitol induced accumulation of the L-PK mRNA even in the absence of insulin. Furthermore, the response to xylitol as well as glucose required the presence of a functional GIRE. It can be assumed from these results that glucose induces the expression of the L-PK gene through the nonoxidative branch of the pentose phosphate pathway. The effect of xylitol at low concentration suggests that the glucose signal to the transcriptional machinery is mediated by xylulose 5-phosphate.
Doiron
B
B
Institut Cochin de Génétique Moléculaire, INSERM, Unité 129, 24 rue du Faubourg Saint Jacques, 75014 Paris, France.
Cuif
M H
MH
Chen
R
R
Kahn
A
A
D000818:Animals; D015152:Blotting, Northern; D002460:Cell Line; D002478:Cells, Cultured; D015500:Chloramphenicol O-Acetyltransferase / Q000096:biosynthesis; D004790:Enzyme Induction; D015870:Gene Expression; D005941:Glucokinase / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology*; D019298:Glucose-6-Phosphate; D005958:Glucosephosphates / Q000032:analysis / Q000378:metabolism; D007527:Isoenzymes / Q000096:biosynthesis*; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D010427:Pentose Phosphate Pathway / Q000187:drug effects; D011770:Pyruvate Kinase / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D015398:Signal Transduction; D014158:Transcription, Genetic; D014993:Xylitol / Q000494:pharmacology*
D005958:Glucosephosphates; D007527:Isoenzymes; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D019298:Glucose-6-Phosphate; D015500:Chloramphenicol O-Acetyltransferase; D005941:Glucokinase; D011770:Pyruvate Kinase; D005947:Glucose; D014993:Xylitol