Conditional expression demonstrates the role of the homeodomain transcription factor Pdx1 in maintenance and regeneration of beta-cells in the adult pancreas
Details
Publication Year 2005-09,Volume 54,Issue #9,Page 2586-2595
Journal Title
DIABETES
Publication Type
Journal Article
Abstract
The homeodomain transcription factor Pdx1 is essential for pancreas development. To investigate the role of Pdx1 in the adult pancreas, we employed a mouse model in which transcription of Pdx1 could be reversibly repressed by administration of doxycycline. Repression of Pdx1 in adult mice impaired expression of insulin and glucagon, leading to diabetes within 14 days. Pdx1 repression was associated with increased cell proliferation predominantly in the exocrine pancreas and up-regulation of genes implicated in pancreas regeneration. Following withdrawal of doxycycline and derepression of Pdx1, normoglycemia was restored within 28 days; during this period, Pdx1(+)/Ins(+) and Pdx(+)/Ins(-) cells were observed in association with the duct epithelia. These findings confirm that Pdx1 is required for R-cell function in the adult (pancreas and indicate that in the absence of Pdx1 expression, a regenerative program is initiated with the potential for Pdx1-dependent beta-cell neogenesis.
Publisher
AMER DIABETES ASSOC
Keywords
EXOCRINE PANCREAS; TRANSGENIC MICE; INSULIN GENE; DIABETES-MELLITUS; PROGENITOR CELLS; IN-VITRO; NEOGENESIS; ISLETS; DIFFERENTIATION; EPITHELIUM
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Creation Date: 2005-09-01 12:00:00
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