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

Autor: Kenji Kohara, Tomohiko Kimura, Hidenori Yoshitaka, Atsushi Obata, Genta Chikazawa, Kentaro Tamura, Arudo Hiraoka, Guy A. Rutter, Saeko Moriuchi, Hideaki Kaneto, Gabriela da Silva Xavier, Hidenori Hirukawa, Atsuhisa Ishida, Tomoatsu Mune, Kohei Kaku, Seizo Okauchi, Ikki Shimizu, Masashi Shimoda
Jazyk: angličtina
Rok vydání: 2018
Předmět:
0301 basic medicine
Male
Small interfering RNA
Receptor expression
lcsh:Medicine
ADHESION
Body Mass Index
Gene expression
RNA
Small Interfering
Receptor
lcsh:Science
Aged
80 and over
Multidisciplinary
GLUCAGON-LIKE PEPTIDE-1
digestive
oral
and skin physiology
Arteriosclerosis
Arteries
Middle Aged
Multidisciplinary Sciences
AGONIST
medicine.anatomical_structure
Science & Technology - Other Topics
CORONARY-ARTERY-DISEASE
Female
Tunica Media
Transcription Factor 7-Like 2 Protein
hormones
hormone substitutes
and hormone antagonists
medicine.medical_specialty
endocrine system
Endothelium
TYPE-2 DIABETES-MELLITUS
Down-Regulation
Article
Glucagon-Like Peptide-1 Receptor
03 medical and health sciences
Downregulation and upregulation
BETA-CELL FUNCTION
Internal medicine
medicine
Human Umbilical Vein Endothelial Cells
Animals
Humans
Obesity
Glucagon-like peptide 1 receptor
Aged
Science & Technology
business.industry
lcsh:R
medicine.disease
ENDOTHELIAL-CELLS
TCF7L2
030104 developmental biology
Endocrinology
ATHEROSCLEROSIS
LIRAGLUTIDE
lcsh:Q
Endothelium
Vascular
business
Tunica Intima
Zdroj: Scientific Reports
Scientific Reports, Vol 8, Iss 1, Pp 1-9 (2018)
ISSN: 2045-2322
Popis: 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.
Databáze: OpenAIRE
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