Abstract
To study the late beta-cell-specific function of the homeodomain protein IPF1/PDX1 we have generated mice in which the Ipf1/Pdx1 gene has been disrupted specifically in beta cells. These mice develop diabetes with age, and we show that IPF1/PDX1 is required for maintaining the beta cell identity by positively regulating insulin and islet amyloid polypeptide expression and by repressing glucagon expression. We also provide evidence that IPF1/PDX1 regulates the expression of Glut2 in a dosage-dependent manner suggesting that lowered IPF1/PDX1 activity may contribute to the development of type II diabetes by causing impaired expression of both Glut2 and insulin.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amyloid / analysis
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Animals
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Blood Glucose / metabolism
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Cell Line
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Diabetes Mellitus, Type 2 / genetics*
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Diabetes Mellitus, Type 2 / metabolism
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Gene Expression Regulation
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Genes / genetics*
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Glucagon / analysis
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Glucose Intolerance
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Glucose Tolerance Test
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Glucose Transporter Type 2
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Heterozygote
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Homeodomain Proteins / analysis
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Immunohistochemistry
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Insulin / metabolism
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Islet Amyloid Polypeptide
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Islets of Langerhans / chemistry
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Islets of Langerhans / growth & development
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Islets of Langerhans / metabolism*
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Mice
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Mice, Inbred C57BL
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Mice, Inbred CBA
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Mice, Mutant Strains
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Monosaccharide Transport Proteins / analysis
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Mutagenesis, Site-Directed
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Phenotype
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Trans-Activators / genetics*
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Trans-Activators / physiology*
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Transcriptional Activation / genetics
Substances
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Amyloid
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Blood Glucose
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Glucose Transporter Type 2
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Homeodomain Proteins
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Insulin
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Islet Amyloid Polypeptide
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Monosaccharide Transport Proteins
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Trans-Activators
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pancreatic and duodenal homeobox 1 protein
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Glucagon