Glucagon-like peptide-1 (GLP-1) inhibits advanced glycation end product (AGE)-induced up-regulation of VCAM-1 mRNA levels in endothelial cells by suppressing AGE receptor (RAGE) expression.

Abstract

Glucagon-like peptide-1 (GLP-1) is one of the incretins, a gut hormone secreted from L cells in the intestine in response to food intake. It has been proposed as a potential therapeutic target for the treatment of patients with type 2 diabetes. However, the direct effects of GLP-1 on vascular injury in diabetes are largely unknown. Since there is a growing body of evidence that advanced glycation end products (AGE) and their receptor RAGE axis plays an important role in vascular complications in diabetes, this study investigated whether and how GLP-1 blocked the deleterious effects of AGE on human umbilical vein endothelial cells (HUVEC). GLP-1 receptor (GLP-1R) was expressed in HUVEC. GLP-1 dose-dependently inhibited RAGE gene expression in HUVEC, which was blocked by small interfering RNAs raised against GLP-1R. An analogue of cyclic AMP also decreased RAGE mRNA level in HUVEC. Further, GLP-1 decreased reactive oxygen species generation and subsequently reduced vascular cell adhesion molecule-1 mRNA levels in AGE-exposed HUVEC. Our present study suggests that GLP-1 directly acts on HUVEC via GLP-1R and it could work as an anti-inflammatory agent against AGE by reducing RAGE expression via activation of cyclic AMP pathways.

• Authors: Yuji Ishibashi, Takanori Matsui, Masayoshi Takeuchi, Sho-Ichi Yamagishi
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 391 Issue 3 Pg. 1405-8 (Jan 15 2010) ISSN: 1090-2104 [Electronic] United States
• PMID: 20026306 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2009 Elsevier Inc. All rights reserved.

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• GLP1R protein, human
• Glucagon-Like Peptide-1 Receptor
• Glycation End Products, Advanced
• RNA, Messenger
• Receptor for Advanced Glycation End Products
• Receptors, Glucagon
• Receptors, Immunologic
• Vascular Cell Adhesion Molecule-1
• Glucagon-Like Peptide 1

Topics

• Anti-Inflammatory Agents, Non-Steroidal (pharmacology)
• Cells, Cultured
• Endothelium, Vascular (drug effects, metabolism)
• Glucagon-Like Peptide 1 (pharmacology)
• Glucagon-Like Peptide-1 Receptor
• Glycation End Products, Advanced (metabolism, pharmacology)
• Humans
• RNA, Messenger (antagonists & inhibitors, biosynthesis)
• Receptor for Advanced Glycation End Products
• Receptors, Glucagon (agonists)
• Receptors, Immunologic (antagonists & inhibitors, biosynthesis)
• Vascular Cell Adhesion Molecule-1 (biosynthesis)