| Critical Role of Egr Transcription Factors in Regulating Insulin Biosynthesis, Blood Glucose Homeostasis, and Islet Size. | |
| | |
MedLine Citation:
|
PMID: 22597533 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
|
Expression of early growth response protein (Egr)-1, a protein of the Egr family of zinc finger transcription factors, is stimulated in glucose-treated pancreatic β-cells and insulinoma cells. The purpose of this study was to elucidate the role of Egr transcription factors in pancreatic β-cells in vivo. To overcome the problem associated with redundancy of functions between Egr proteins, conditional transgenic mice were generated expressing a dominant-negative mutant of Egr-1 in pancreatic β-cells. The Egr-1 mutant interferes with DNA binding of all Egr proteins and thus impairs the biological functions of the entire Egr family. Expression of the Egr-1 mutant reduced expression of TGFβ and basic fibroblast growth factor, known target genes of Egr-1, whereas the expression of Egr-1, Egr-3, Ets-like gene-1, and specificity protein-3 was not changed in the presence of the Egr-1 mutant. Expression of the homeobox protein pancreas duodenum homeobox-1, a major regulator of insulin biosynthesis, was reduced in islets expressing the Egr-1 mutant. Accordingly, insulin mRNA and protein levels were reduced by 75 or 25%, respectively, whereas expression of glucagon and somatostatin was not altered after expression of the Egr-1 mutant in β-cells. Glucose tolerance tests revealed that transgenic mice expressing the Egr-1 mutant in pancreatic β-cells displayed impaired glucose tolerance. In addition, increased caspase-3/7 activity was detected as a result of transgene expression, leading to a 20% decrease of the size of the islets. These results show that Egr proteins play an important role in controlling insulin biosynthesis, glucose homeostasis, and islet size of pancreatic β-cells in vivo. |
| | |
Authors:
|
Isabelle Müller; Oliver G Rössler; Christine Wittig; Michael D Menger; Gerald Thiel |
Related Documents
:
|
9438383 - P27kip1 is expressed transiently in developing myotomes and enhances myogenesis. 14659813 - Differential cyclin e expression in human in-stent stenosis smooth muscle cells identif... 9730973 - Dichotomous development of the organic anion transport protein in liver and choroid ple... |
Publication Detail:
|
Type: JOURNAL ARTICLE Date: 2012-5-17 |
Journal Detail:
|
Title: Endocrinology Volume: - ISSN: 1945-7170 ISO Abbreviation: - Publication Date: 2012 May |
Date Detail:
|
Created Date: 2012-5-18 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 0375040 Medline TA: Endocrinology Country: - |
Other Details:
|
Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
|
Departments of Medical Biochemistry and Molecular Biology (I.M., O.G.R., G.T.), and Clinical and Experimental Surgery (C.W., M.D.M.), University of Saarland Medical Center, D-66421 Homburg, Germany. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: The scatter of research: cross sectional comparison of randomised trials and systematic reviews acro...
Next Document: Dihydrotestosterone Inhibits Lectin-Like Oxidized-LDL Receptor-1 Expression in Aortic Endothelial Ce...