Overexpression of the Pdx-1 homeodomain transcription factor impairs glucose metabolism in cultured rat hepatocytes.
The Pdx-1 transcription factor plays crucial functions both during pancreas development and in the adult beta cells. Previous studies have indicated that ectopic Pdx-1 expression in liver or intestinal primary and immortalized cells is sufficient to promote activation of insulin gene expression. This work is focused on the molecular and physiological consequences of Pdx-1 overexpression in liver cells. We present evidence that Pdx-1 affects the level of expression of one of the four mammalian hexokinase isozymes. These are glucose phosphorylating enzymes involved in essential cellular functions such as glucose sensing, metabolic energy production and apoptosis. Specifically, our data show that over-expression of Pdx-1 in cultured hepatocytes is able to repress the expression of hexokinase 2 (Hxk 2) and the phenomenon is mediated via binding of Pdx-1 to a specific sequence on the Hxk 2 gene promoter. As a consequence, liver cells over-expressing Pdx-1 present interesting alterations concerning glucose metabolism.
Pillich
Rudolf Tito
RT
Dipartimento di Biologia Cellulare e dello Sviluppo, Sapienza Università di Roma, P.le Aldo Moro, Roma, Italy.
Scarsella
Gianfranco
G
Risuleo
Gianfranco
G
D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D024202:Electrophoretic Mobility Shift Assay; D005947:Glucose / Q000378:metabolism*; D006003:Glycogen / Q000096:biosynthesis; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D015345:Oligonucleotide Probes / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014162:Transfection
D018398:Homeodomain Proteins; D007004:Hypoglycemic Agents; D007328:Insulin; D015345:Oligonucleotide Probes; D015534:Trans-Activators; C084010:pancreatic and duodenal homeobox 1 protein; D006003:Glycogen; D005947:Glucose