Serum Level of Soluble Receptor for Advanced Glycation End Products Is Associated with A Disintegrin And Metalloproteinase 10 in Type 1 Diabetes

The receptor for advanced glycation end products (RAGE) is involved in the pathogenesis of diabetic complications, and soluble forms of the receptor (sRAGE) can counteract the detrimental action of the full-length receptor by acting as decoy. Soluble RAGE is produced by alternative splicing [endogen...

Full description

Saved in:
Bibliographic Details
Published in:PloS one 2015-09, Vol.10 (9), p.e0137330-e0137330
Main Authors: Lee, Alan C H, Lam, Joanne K Y, Shiu, Sammy W M, Wong, Ying, Betteridge, D John, Tan, Kathryn C B
Format: Article
Language:English
Subjects:
ADAM Proteins - blood
ADAM10 Protein
Adult
Advanced glycation end products
Advanced glycosylation end products
Alternative splicing
Amyloid Precursor Protein Secretases - blood
Atherosclerosis
Biology
Body mass
Cleavage
Complications
Development and progression
Diabetes
Diabetes mellitus
Diabetes Mellitus, Type 1 - blood
Disease
Enzyme-linked immunosorbent assay
Experiments
Female
Genetic aspects
Glucose
Glycosylation
Hemoglobin
Humans
Insulin
Kinases
Macrophages
Male
Medical research
Medicine
Membrane Proteins - blood
Metalloenzymes
Middle Aged
Pathogenesis
Physiological aspects
Protein expression
Proteins
Proteolysis
Receptor for Advanced Glycation End Products - blood
Rodents
Shedding
Smoking
Studies
Type 1 diabetes
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The receptor for advanced glycation end products (RAGE) is involved in the pathogenesis of diabetic complications, and soluble forms of the receptor (sRAGE) can counteract the detrimental action of the full-length receptor by acting as decoy. Soluble RAGE is produced by alternative splicing [endogenous secretory RAGE (esRAGE)] and/or by proteolytic cleavage of the membrane-bound receptor. We have investigated the role of A Disintegrin And Metalloproteinase 10 (ADAM10) in the ectodomain shedding of RAGE. Constitutive and insulin-induced shedding of RAGE in THP-1 macrophages by ADAM10 was evaluated using an ADAM10-specific metalloproteinase inhibitor. Serum ADAM10 level was measured in type 1 diabetes and control subjects, and the association with serum soluble RAGE was determined. Serum total sRAGE and esRAGE were assayed by ELISA and the difference between total sRAGE and esRAGE gave an estimated measure of soluble RAGE formed by cleavage (cRAGE). RAGE shedding (constitutive and insulin-induced) was significantly reduced after inhibition of ADAM10 in macrophages, and insulin stimulated ADAM10 expression and activity. Diabetic subjects have higher serum total sRAGE and esRAGE (p
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0137330