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Title: The glucagon-like peptide 1 receptor agonist enhances intrinsic peroxisome proliferator-activated receptor γ activity in endothelial cells

Abstract

Highlights: • PPARγ activation was involved in the GLP-1-mediated anti-inflammatory action. • Exendin-4 enhanced endogenous PPARγ transcriptional activity in HUVECs. • H89, a PKA inhibitor, abolished GLP-1-induced PPARγ enhancement. • The anti-inflammatory effects of GLP-1 may be explained by PPARγ activation. - Abstract: Recent studies have suggested glucagon-like peptide-1 (GLP-1) signaling to exert anti-inflammatory effects on endothelial cells, although the precise underlying mechanism remains to be elucidated. In the present study, we investigated whether PPARγ activation is involved in the GLP-1-mediated anti-inflammatory action on endothelial cells. When we treated HUVEC cells with 0.2 ng/ml exendin-4, a GLP-1 receptor agonist, endogenous PPARγ transcriptional activity was significantly elevated, by approximately 20%, as compared with control cells. The maximum PPARγ activity enhancing effect of exendin-4 was observed 12 h after the initiation of incubation with exendin-4. As H89, a PKA inhibitor, abolished GLP-1-induced PPARγ enhancement, the signaling downstream from GLP-1 cross-talk must have been involved in PPARγ activation. In conclusion, our results suggest that GLP-1 has the potential to induce PPARγ activity, partially explaining the anti-inflammatory effects of GLP-1 on endothelial cells. Cross-talk between GLP-1 signaling and PPARγ activation would have major impacts on treatments for patients at high risk for cardiovascular disease.

Authors:
; ; ; ; ; ; ; ; ; ;
Publication Date:
OSTI Identifier:
22416722
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 451; Journal Issue: 2; Other Information: Copyright (c) 2014 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ADHESION; CARDIOVASCULAR DISEASES; COMPARATIVE EVALUATIONS; GLUCAGON; HOMEOSTASIS; HUMAN POPULATIONS; INCUBATION; INFLAMMATION; INSULIN; MOLECULES; NADP; OXIDASES; PATIENTS; PHOSPHATES; PLASMINOGEN; RECEPTORS; SUBSTRATES; VEINS

Citation Formats

Onuma, Hirohisa, Inukai, Kouichi, E-mail: kinukai@ks.kyorin-u.ac.jp, Kitahara, Atsuko, Moriya, Rie, Nishida, Susumu, Tanaka, Toshiaki, Katsuta, Hidenori, Takahashi, Kazuto, Sumitani, Yoshikazu, Hosaka, Toshio, and Ishida, Hitoshi. The glucagon-like peptide 1 receptor agonist enhances intrinsic peroxisome proliferator-activated receptor γ activity in endothelial cells. United States: N. p., 2014. Web. doi:10.1016/J.BBRC.2014.07.136.
Onuma, Hirohisa, Inukai, Kouichi, E-mail: kinukai@ks.kyorin-u.ac.jp, Kitahara, Atsuko, Moriya, Rie, Nishida, Susumu, Tanaka, Toshiaki, Katsuta, Hidenori, Takahashi, Kazuto, Sumitani, Yoshikazu, Hosaka, Toshio, & Ishida, Hitoshi. The glucagon-like peptide 1 receptor agonist enhances intrinsic peroxisome proliferator-activated receptor γ activity in endothelial cells. United States. doi:10.1016/J.BBRC.2014.07.136.
Onuma, Hirohisa, Inukai, Kouichi, E-mail: kinukai@ks.kyorin-u.ac.jp, Kitahara, Atsuko, Moriya, Rie, Nishida, Susumu, Tanaka, Toshiaki, Katsuta, Hidenori, Takahashi, Kazuto, Sumitani, Yoshikazu, Hosaka, Toshio, and Ishida, Hitoshi. Fri . "The glucagon-like peptide 1 receptor agonist enhances intrinsic peroxisome proliferator-activated receptor γ activity in endothelial cells". United States. doi:10.1016/J.BBRC.2014.07.136.
@article{osti_22416722,
title = {The glucagon-like peptide 1 receptor agonist enhances intrinsic peroxisome proliferator-activated receptor γ activity in endothelial cells},
author = {Onuma, Hirohisa and Inukai, Kouichi, E-mail: kinukai@ks.kyorin-u.ac.jp and Kitahara, Atsuko and Moriya, Rie and Nishida, Susumu and Tanaka, Toshiaki and Katsuta, Hidenori and Takahashi, Kazuto and Sumitani, Yoshikazu and Hosaka, Toshio and Ishida, Hitoshi},
abstractNote = {Highlights: • PPARγ activation was involved in the GLP-1-mediated anti-inflammatory action. • Exendin-4 enhanced endogenous PPARγ transcriptional activity in HUVECs. • H89, a PKA inhibitor, abolished GLP-1-induced PPARγ enhancement. • The anti-inflammatory effects of GLP-1 may be explained by PPARγ activation. - Abstract: Recent studies have suggested glucagon-like peptide-1 (GLP-1) signaling to exert anti-inflammatory effects on endothelial cells, although the precise underlying mechanism remains to be elucidated. In the present study, we investigated whether PPARγ activation is involved in the GLP-1-mediated anti-inflammatory action on endothelial cells. When we treated HUVEC cells with 0.2 ng/ml exendin-4, a GLP-1 receptor agonist, endogenous PPARγ transcriptional activity was significantly elevated, by approximately 20%, as compared with control cells. The maximum PPARγ activity enhancing effect of exendin-4 was observed 12 h after the initiation of incubation with exendin-4. As H89, a PKA inhibitor, abolished GLP-1-induced PPARγ enhancement, the signaling downstream from GLP-1 cross-talk must have been involved in PPARγ activation. In conclusion, our results suggest that GLP-1 has the potential to induce PPARγ activity, partially explaining the anti-inflammatory effects of GLP-1 on endothelial cells. Cross-talk between GLP-1 signaling and PPARγ activation would have major impacts on treatments for patients at high risk for cardiovascular disease.},
doi = {10.1016/J.BBRC.2014.07.136},
journal = {Biochemical and Biophysical Research Communications},
number = 2,
volume = 451,
place = {United States},
year = {Fri Aug 22 00:00:00 EDT 2014},
month = {Fri Aug 22 00:00:00 EDT 2014}
}