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Positive association between serum levels of advanced glycation end products and the soluble form of receptor for advanced glycation end products in nondiabetic subjects
Abstract
The advanced glycation end products (AGEs)-receptor for AGE (RAGE) axis is implicated in diabetic vascular complications. Administration of soluble form of RAGE (sRAGE) to mice has been shown to block the AGE-elicited tissue damage by acting as a decoy. These observations suggest that endogenous sRAGE may capture and eliminate circulating AGEs and decrease its serum levels. However, because AGEs up-regulate tissue RAGE expression and endogenous sRAGE could be generated from the cleavage of cell surface RAGE, sRAGE may be positively, rather than inversely, associated with circulating AGEs by reflecting tissue RAGE expression. In this study, we investigated the association of sRAGE with serum levels of AGEs in humans. Data for fasting serum sRAGE and AGE levels of 184 nondiabetic subjects were obtained from a general population in Japan. We also measured body mass index (BMI), waist circumference, blood pressure, and blood biochemistries in this population. Uni- and multivariate analyses were applied for the determinants of serum sRAGE levels. The average sRAGE levels were 0.40 +/- 0.17 ng/mL in males and 0.43 +/- 0.14 ng/mL in females, respectively. In the univariate analysis, BMI (P < .05, inversely), waist circumference (P < .05, inversely), AGEs (P < .05), and alcohol intake (P < .05, inversely) were significantly associated with sRAGE levels. After performing multivariate analyses, BMI (P < .05, inversely) and AGEs (P < .05) still remained significant independently. The present study is the first demonstration that serum sRAGE levels were positively associated with circulating AGEs in the nondiabetic general population. Endogenous sRAGE levels are elevated in parallel with serum AGE levels.
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“Furthermore, the soluble forms of the RAGE competitively bind AGEs preventing their interaction with mRAGE and the activation of downstream pathways, including pro-inflammatory responses.[42,43]”
From The Role of Dietary Advanced Glycation End Products in Metabolic Dysfunction (2021) · cites this paper as [43]
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Metadata
- Authors
- Yamagishi, S.-I., Adachi, H., Nakamura, K., Matsui, T., Jinnouchi, Y., Takenaka, K., Takeuchi, M., Enomoto, M., Furuki, K., Hino, A., Shigeto, Y., & Imaizumi, T.
- Affiliations
- Kurume University (JP)
- Hokuriku University (JP)
- Corresponding author
- Yamagishi, Sho-ichi
- Venue
- Metabolism
- Publisher
- Elsevier BV
- Published
- 2006-09
- Volume
- 55
- Issue
- 9
- Pages
- 1227-1231
- ISSN
- 0026-0495 (ISSN-L)
- OpenAlex
- W2042667331
- Cited by
- 148
- References
- 33
- Citations by year
- 2026: 3 · 2024: 2 · 2023: 3 · 2022: 7 · 2021: 5 · 2020: 7 · 2019: 7 · 2018: 1 · 2017: 5 · 2016: 13 · 2015: 7 · 2014: 11 · 2013: 7 · 2012: 9
- FWCI
- 9.80
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Education, Culture, Sports, Science and Technology
- Kimura Memorial Heart Foundation
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Advanced Glycation End Products research
- Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- advanced glycation end products, soluble receptor for advanced glycation end products, non-diabetic patients, body mass index, waist circumference, alcohol consumption, diabetic vascular complications, AGE-RAGE axis
- MeSH terms
- Receptor for Advanced Glycation End Products, Aged, Alcohol Drinking, Analysis of Variance, Blood Chemical Analysis, Blood Pressure, Female, Humans, Japan, Male, Middle Aged, Receptors, Immunologic, Solubility, Body Mass Index, Glycation End Products, Advanced, Body Size
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