Down-regulation of vascular GLP-1 receptor expression in human subjects with obesity

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Title: Down-regulation of vascular GLP-1 receptor expression in human subjects with obesity
Authors: Kimura, T
Obata, A
Shimoda, M
Shimizu, I
Xavier, GDS
Okauchi, S
Hirukawa, H
Kohara, K
Mune, T
Moriuchi, S
Hiraoka, A
Tamura, K
Chikazawa, G
Ishida, A
Yoshitaka, H
Rutter, GA
Kaku, K
Kaneto, H
Item Type: Journal Article
Abstract: It has been thought that incretin signaling prevents arteriosclerosis, and very recently anti-arteriosclerotic effects through GLP-1 receptor were finally demonstrated in clinical human study. The purpose of this study was to investigate how vascular GLP-1 receptor expression is influenced in human subjects. First, we evaluated GLP-1 receptor expression in human arteries in immunostaining. Next, we separated the artery into the intima and media, and evaluated gene expression levels of various factors. We divided the subjects into obesity and non-obesity group and compared their expression levels between them. Finally, we evaluated which factors determine vascular GLP-1 receptor expression. GLP-1 receptor expression in intima and media was lower in obesity group compared to non-obesity group which was correlated with the alteration of TCF7L2 expression. Multiple regression analyses showed that BMI was an independent determining factor for GLP-1 receptor expression in the intima and media. Furthermore, using small interfering RNA method and TCF7L2-EGFP adenovirus, we showed that TCF7L2 was involved in GLP-1 receptor expression in human vascular cells. Taken together, vascular GLP-1 receptor and TCF7L2 expression was significantly down-regulated in human subjects with obesity. In addition, it is likely that TCF7L2 functions as a modulator of vascular GLP-1 receptor expression.
Issue Date: 13-Jul-2018
Date of Acceptance: 2-Jul-2018
ISSN: 2045-2322
Publisher: Nature Publishing Group
Journal / Book Title: Scientific Reports
Volume: 8
Issue: 1
Copyright Statement: © 2018 The Author(s). This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit
Keywords: Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
Publication Status: Published
Article Number: 10644
Online Publication Date: 2018-07-13
Appears in Collections:Department of Medicine
Faculty of Medicine

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