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PMID: 9637677 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

beta-cell-specific inactivation of the mouse Ipf1/Pdx1 gene results in loss of the beta-cell phenotype and maturity onset diabetes.

Genes & development ·Vol. 12 ·No. 12 ·1998-06-15 ·Pages 1763-8

Ahlgren U, Jonsson J, Jonsson L, Simu K, Edlund H

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.

MeSH Terms

Amyloid/analysis Animals Blood Glucose/metabolism Cell Line Diabetes Mellitus, Type 2/genetics,metabolism Gene Expression Regulation Genes/genetics Glucagon/analysis Glucose Intolerance Glucose Tolerance Test Glucose Transporter Type 2 Heterozygote Homeodomain Proteins/analysis Immunohistochemistry Insulin/metabolism Islet Amyloid Polypeptide Islets of Langerhans/chemistry,growth & development,metabolism Mice Mice, Inbred C57BL Mice, Inbred CBA Mice, Mutant Strains Monosaccharide Transport Proteins/analysis Mutagenesis, Site-Directed Phenotype Trans-Activators/genetics,physiology Transcriptional Activation/genetics

Chemicals

Amyloid Blood Glucose Glucose Transporter Type 2 Homeodomain Proteins Insulin Islet Amyloid Polypeptide Monosaccharide Transport Proteins Trans-Activators pancreatic and duodenal homeobox 1 protein Glucagon

Authors & Affiliations

5 authors, click to expand affiliations / ORCID

Ahlgren U

Department of Microbiology, University of Umeâ, S-901 87 Umeâ, Sweden.

Jonsson J

Jonsson L

Simu K

Edlund H

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35 references, click to expand

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Article Info

Journal

Genes & development

Abbr.

Genes Dev

ISSN

0890-9369

DOI

10.1101/gad.12.12.1763

Published

1998-06-15

Pages

1763-8

Language

English

Region

United States

NLM ID

8711660

PMCID

PMC316911

Subset

External Links

PubMed source DOI: 10.1101/gad.12.12.1763 PMC Full Text View journal details

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beta-cell-specific inactivation of the mouse Ipf1/Pdx1 gene results in loss of the beta-cell phenotype and maturity onset diabetes.

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