The loss of GLUT2 expression in the pancreatic beta-cells of diabetic db/db mice is associated with an impaired DNA-binding activity of islet-specific trans-acting factors.

Détails

ID Serval
serval:BIB_5F54DCA36FB6
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
The loss of GLUT2 expression in the pancreatic beta-cells of diabetic db/db mice is associated with an impaired DNA-binding activity of islet-specific trans-acting factors.
Périodique
Molecular and Cellular Endocrinology
Auteur(s)
Bonny C., Roduit R., Gremlich S., Nicod P., Thorens B., Waeber G.
ISSN
0303-7207
ISSN-L
0303-7207
Statut éditorial
Publié
Date de publication
1997
Peer-reviewed
Oui
Volume
135
Numéro
1
Pages
59-65
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
GLUT2 expression is reduced in the pancreatic beta-cells of several diabetic animals. The transcriptional control of the gene in beta-cells involves at least two islet-specific DNA-binding proteins, GTIIa and PDX-1, which also transactivates the insulin, somatostatin and glucokinase genes. In this report, we assessed the DNA-binding activities of GTIIa and PDX-1 to their respective cis-elements of the GLUT2 promoter using nuclear extracts prepared from pancreatic islets of 12 week old db/db diabetic mice. We show that the decreased GLUT2 mRNA expression correlates with a decrease of the GTIIa DNA-binding activity, whereas the PDX-1 binding activity is increased. In these diabetic animals, insulin mRNA expression remains normal. The adjunction of dexamethasone to isolated pancreatic islets, a treatment previously shown to decrease PDX-1 expression in the insulin-secreting HIT-T15 cells, has no effect on the GTIIa and PDX-1 DNA-binding activities. These data suggest that the decreased activity of GTIIa, in contrast to PDX-1, may be a major initial step in the development of the beta-cell dysfunction in this model of diabetes.
Mots-clé
Animals, DNA/metabolism, Diabetes Mellitus/metabolism, Gene Expression, Glucose Transporter Type 2, Homeodomain Proteins, Insulin/genetics, Islets of Langerhans/metabolism, Male, Mice, Monosaccharide Transport Proteins/genetics, RNA, Messenger/metabolism, Rats, Rats, Sprague-Dawley, Trans-Activators/metabolism
Pubmed
Web of science
Création de la notice
24/01/2008 14:41
Dernière modification de la notice
20/08/2019 15:17
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