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

Hirohisa Onuma; Kouichi Inukai; Atsuko Kitahara; Rie Moriya; Susumu Nishida; Toshiaki Tanaka; Hidenori Katsuta; Kazuto Takahashi; Yoshikazu Sumitani; Toshio Hosaka; Hitoshi Ishida

doi:10.1016/j.bbrc.2014.07.136

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

Biochem Biophys Res Commun. 2014 Aug 22;451(2):339-44. doi: 10.1016/j.bbrc.2014.07.136. Epub 2014 Aug 7.

Affiliations

¹ Third Department of Internal Medicine, Division of Diabetes, Endocrinology and Metabolism, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka, Tokyo, Japan.
² Third Department of Internal Medicine, Division of Diabetes, Endocrinology and Metabolism, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka, Tokyo, Japan. Electronic address: [email protected].

PMID: 25109805
DOI: 10.1016/j.bbrc.2014.07.136

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 0.2ng/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 12h 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.

Keywords: GLP-1; HUVEC; PPARγ.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anilides / pharmacology
Colforsin / pharmacology
Cyclic AMP-Dependent Protein Kinases / antagonists & inhibitors
Cyclic AMP-Dependent Protein Kinases / metabolism
Endothelial Cells / drug effects*
Endothelial Cells / metabolism*
Exenatide
Gene Expression / drug effects
Glucagon-Like Peptide-1 Receptor
Human Umbilical Vein Endothelial Cells
Humans
Intercellular Adhesion Molecule-1 / genetics
Intercellular Adhesion Molecule-1 / metabolism
Isoquinolines / pharmacology
NADPH Oxidase 1
NADPH Oxidases / genetics
NADPH Oxidases / metabolism
NF-kappa B / metabolism
PPAR gamma / antagonists & inhibitors
PPAR gamma / metabolism*
Peptides / pharmacology*
Phosphorylation
Pioglitazone
Protein Kinase Inhibitors / pharmacology
Receptor Cross-Talk
Receptors, Glucagon / agonists*
Signal Transduction / drug effects
Sulfonamides / pharmacology
Thiazolidinediones / pharmacology
Vascular Cell Adhesion Molecule-1 / genetics
Vascular Cell Adhesion Molecule-1 / metabolism
Venoms / pharmacology*

Substances

2-chloro-5-nitrobenzanilide
Anilides
GLP1R protein, human
Glucagon-Like Peptide-1 Receptor
ICAM1 protein, human
Isoquinolines
NF-kappa B
PPAR gamma
Peptides
Protein Kinase Inhibitors
Receptors, Glucagon
Sulfonamides
Thiazolidinediones
Vascular Cell Adhesion Molecule-1
Venoms
Intercellular Adhesion Molecule-1
Colforsin
Exenatide
NADPH Oxidase 1
NADPH Oxidases
NOX1 protein, human
Cyclic AMP-Dependent Protein Kinases
N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide
Pioglitazone