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Molecules 2008, 13(10), 2659-2673; doi:10.3390/molecules13102659

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

Received: 30 September 2008 / Revised: 20 October 2008 / Accepted: 24 October 2008 / Published: 28 October 2008
(This article belongs to the Special Issue Nucleic Acids)
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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.
Keywords: Pdx-1; Hexokinase-2; Transcriptional promoters; Glucose metabolism Pdx-1; Hexokinase-2; Transcriptional promoters; Glucose metabolism
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Pillich, R.T.; Scarsella, G.; Risuleo, G. Overexpression of the Pdx-1 Homeodomain Transcription Factor Impairs Glucose Metabolism in Cultured Rat Hepatocytes. Molecules 2008, 13, 2659-2673.

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