title: The glucagon-like peptide 1 receptor agonist enhances intrinsic peroxisome proliferator-activated receptor γ activity in endothelial cells.
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.
authors.affiliation: Third Department of Internal Medicine, Division of Diabetes, Endocrinology and Metabolism, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka, Tokyo, Japan.
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Onuma
authors.affiliation: 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: kinukai@ks.kyorin-u.ac.jp.
authors.forename: Kouichi
authors.initials: K
authors.lastname: Inukai
authors.affiliation: Third Department of Internal Medicine, Division of Diabetes, Endocrinology and Metabolism, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka, Tokyo, Japan.
authors.forename: Atsuko
authors.initials: A
authors.lastname: Kitahara
authors.affiliation: Third Department of Internal Medicine, Division of Diabetes, Endocrinology and Metabolism, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka, Tokyo, Japan.
authors.forename: Rie
authors.initials: R
authors.lastname: Moriya
authors.affiliation: Third Department of Internal Medicine, Division of Diabetes, Endocrinology and Metabolism, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka, Tokyo, Japan.
authors.forename: Susumu
authors.initials: S
authors.lastname: Nishida
authors.affiliation: Third Department of Internal Medicine, Division of Diabetes, Endocrinology and Metabolism, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka, Tokyo, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Tanaka
authors.affiliation: Third Department of Internal Medicine, Division of Diabetes, Endocrinology and Metabolism, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka, Tokyo, Japan.
authors.forename: Hidenori
authors.initials: H
authors.lastname: Katsuta
authors.affiliation: Third Department of Internal Medicine, Division of Diabetes, Endocrinology and Metabolism, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka, Tokyo, Japan.
authors.forename: Kazuto
authors.initials: K
authors.lastname: Takahashi
authors.affiliation: Third Department of Internal Medicine, Division of Diabetes, Endocrinology and Metabolism, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka, Tokyo, Japan.
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Sumitani
authors.affiliation: Third Department of Internal Medicine, Division of Diabetes, Endocrinology and Metabolism, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka, Tokyo, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Hosaka
authors.affiliation: Third Department of Internal Medicine, Division of Diabetes, Endocrinology and Metabolism, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka, Tokyo, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Ishida
mesh_terms: D000813:Anilides / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism*; D000077270:Exenatide; D015870:Gene Expression / Q000187:drug effects; D000067757:Glucagon-Like Peptide-1 Receptor; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D007546:Isoquinolines / Q000494:pharmacology; D000074624:NADPH Oxidase 1; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D047495:PPAR gamma / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010455:Peptides / Q000494:pharmacology*; D010766:Phosphorylation; D000077205:Pioglitazone; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D020239:Receptor Cross-Talk; D018027:Receptors, Glucagon / Q000819:agonists*; D015398:Signal Transduction / Q000187:drug effects; D013449:Sulfonamides / Q000494:pharmacology; D045162:Thiazolidinediones / Q000494:pharmacology; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D014688:Venoms / Q000494:pharmacology*
chemical_list: C457499:2-chloro-5-nitrobenzanilide; D000813:Anilides; C000593833:GLP1R protein, human; D000067757:Glucagon-Like Peptide-1 Receptor; C573420:ICAM1 protein, human; D007546:Isoquinolines; D016328:NF-kappa B; D047495:PPAR gamma; D010455:Peptides; D047428:Protein Kinase Inhibitors; D018027:Receptors, Glucagon; D013449:Sulfonamides; D045162:Thiazolidinediones; D019010:Vascular Cell Adhesion Molecule-1; D014688:Venoms; D018799:Intercellular Adhesion Molecule-1; D005576:Colforsin; D000077270:Exenatide; D000074624:NADPH Oxidase 1; D019255:NADPH Oxidases; C402799:NOX1 protein, human; D017868:Cyclic AMP-Dependent Protein Kinases; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide; D000077205:Pioglitazone
keywords: GLP-1; HUVEC; PPARγ