Glucose represses PPARα gene expression via AMP-activated protein kinase but not via p38 mitogen-activated protein kinase in the pancreatic β-cell.

Détails

ID Serval
serval:BIB_802A55897AFA
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Glucose represses PPARα gene expression via AMP-activated protein kinase but not via p38 mitogen-activated protein kinase in the pancreatic β-cell.
Périodique
Journal of diabetes
Auteur(s)
Joly E., Roduit R., Peyot M.L., Habinowski S.A., Ruderman N.B., Witters L.A., Prentki M.
ISSN
1753-0407 (Electronic)
ISSN-L
1753-0407
Statut éditorial
Publié
Date de publication
12/2009
Peer-reviewed
Oui
Volume
1
Numéro
4
Pages
263-272
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
Peroxisome proliferator-activated receptor α (PPARα) regulates the expression of fatty acid metabolism genes and is thought to play a role in the regulation of insulin secretion and lipid detoxification. We have examined the mechanism whereby glucose decreases PPARα gene expression in the pancreatic β-cell.
INS832/13 β-cell and isolated rat islets were incubated at 3 and 20 mM glucose for 18 h in the absence or presence of adenosine monophosphate (AMP)-activated protein kinase (AMPK) activators and inhibitors, as well as p38 mitogen-activated protein kinase (p38 MAPK) inhibitors. In another set of experiments, INS832/13 were infected with an adenovirus expressing a dominant-negative form of AMPK. PPARα expression levels were measured by reverse transcription polymerase chain reaction and Western blot.
Elevated glucose reduced the abundance of the PPARα transcript and protein, and its target genes acyl-coenzyme A (CoA) oxidase (ACO) and uncoupling protein 2 (UCP-2) in INS832/13 β-cell and isolated rat islets. Glucose reduced AMPK activity, while the AMPK activators 5-amino-4-imidazolecarboxamide riboside and metformin increased PPARα expression and suppressed the action of glucose. By contrast, the AMPK inhibitor compound C mimicked the glucose effect. A dominant negative form of AMPKα reduced the PPARα, ACO and UCP-2 transcripts to the same extent as elevated glucose. Pharmacological evidence indicated that glucose-regulated PPARα expression does not involve p38 MAPK, a target of AMPK in several cell types.
The results indicate that glucose represses PPARα gene expression via AMPK, but not via p38 MAPK in the β-cell.

Mots-clé
AMP-Activated Protein Kinases/metabolism, Animals, DNA Primers, Down-Regulation, Gene Expression/drug effects, Glucose/pharmacology, Islets of Langerhans/drug effects, Islets of Langerhans/enzymology, Islets of Langerhans/physiology, PPAR alpha/drug effects, PPAR alpha/genetics, Rats, Reverse Transcriptase Polymerase Chain Reaction, Transcription, Genetic/drug effects, p38 Mitogen-Activated Protein Kinases/metabolism
Pubmed
Web of science
Open Access
Oui
Création de la notice
07/09/2017 15:14
Dernière modification de la notice
20/08/2019 15:40
Données d'usage