overexpression of the pdx-1 homeodomain transcription factor impairs glucose metabolism in cultured rat hepatocytes过度的pdx-1 homeodomain转录因子损害在培养大鼠肝细胞葡萄糖代谢.pdfVIP

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overexpression of the pdx-1 homeodomain transcription factor impairs glucose metabolism in cultured rat hepatocytes过度的pdx-1 homeodomain转录因子损害在培养大鼠肝细胞葡萄糖代谢.pdf

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overexpression of the pdx-1 homeodomain transcription factor impairs glucose metabolism in cultured rat hepatocytes过度的pdx-1 homeodomain转录因子损害在培养大鼠肝细胞葡萄糖代谢

Molecules 2008, 13, 2659-2673; DOI: 10.3390/molecule OPEN ACCESS molecules ISSN 1420-3049 /journal/molecules Article Overexpression of the Pdx-1 Homeodomain Transcription Factor Impairs Glucose Metabolism in Cultured Rat Hepatocytes Rudolf Tito Pillich 1, Gianfranco Scarsella 1 and Gianfranco Risuleo 2,* 1 Dipartimento di Biologia Cellulare e dello Sviluppo, Sapienza Università di Roma, P.le Aldo Moro, 5 – 00185 Roma, Italy; E-mail: rpillich@ (R-T. P.), gianfranco.scarsella@uniroma1.it (G. S.) 2 Dipartimento di Genetica e Biologia Molecolare, Sapienza Università di Roma, P.le Aldo Moro, 5 – 00185 Roma, Italy * Author to whom correspondence should be addressed; E-mails: gianfranco.risuleo@uniroma1.it or gianfranco.risuleo@asi.it; Tel.: +39 0649912234; Fax: +39 064440812. Received: 30 September 2008; in revised form: 20 October 2008 / Accepted: 24 October 2008 / Published: 28 October 2008 Abstract: 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 phosp