Overexpression of the Pdx-1 Homeodomain Transcription Factor Impairs Glucose Metabolism in Cultured Rat Hepatocytes

Molecules

Rudolf Tito Pillich¹  Gianfranco Scarsella¹ 

[1] Dipartimento di Biologia Cellulare e dello Sviluppo, Sapienza Università di Roma, P.le Aldo Moro, 5 – 00185 Roma, Italy; E-mails:

关键词: Pdx-1;    Hexokinase-2;    Transcriptional promoters;    Glucose metabolism;   

DOI  :  10.3390/molecules13102659

来源: mdpi

【 摘 要 】

The Pdx-1 transcription factor plays crucial functions both during pancreas development and in the adult β 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.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.