Role of methylglyoxal adducts in the development of vascular complications in diabetes mellitus

2003 ◽  
Vol 31 (6) ◽  
pp. 1400-1402 ◽  
Author(s):  
M. Bourajjaj ◽  
C.D.A. Stehouwer ◽  
V.W.M. van Hinsbergh ◽  
C.G. Schalkwijk
Keyword(s):  
Diabetes Mellitus ◽  
Advanced Glycation End Products ◽  
Vascular Complications ◽  
Advanced Glycation ◽  
Exact Role ◽  
Dicarbonyl Compound ◽  
Diabetic Vascular Complications ◽  
Glycation End Products ◽  
End Products

Various theories have been proposed to explain the hyperglycaemia-induced pathogenesis of vascular complications of diabetes, including detrimental effects of AGEs (advanced glycation end products) on vascular tissues. Increased formation of the very reactive dicarbonyl compound MGO (methylglyoxal), one of the side-products of glycolysis, and MGO-derived AGEs seem to be implicated in the development of diabetic vascular complications. Although the exact role of MGO and MGO adducts in the development of vascular complications is unknown, receptor-mediated activation of vascular cells by the MGO–arginine adduct hydroimidazolone, as well as intracellular modifications of protein by MGO, seem to be involved. The aim of this mini-review is to assess to what extent MGO is related to vascular complications in diabetes.

scholarly journals Advanced glycation end products induce a prothrombotic phenotype in mice via interaction with platelet CD36

Blood ◽  
2012 ◽  
Vol 119 (25) ◽  
pp. 6136-6144 ◽  
Author(s):  
Weifei Zhu ◽  
Wei Li ◽  
Roy L. Silverstein
Keyword(s):  
Diabetes Mellitus ◽  
Mouse Models ◽  
Advanced Glycation End Products ◽  
Vascular Complications ◽  
Dependent Manner ◽  
Advanced Glycation ◽  
Drug Induced ◽  
Glycation End Products ◽  
End Products

Abstract Diabetes mellitus has been associated with platelet hyperreactivity, which plays a central role in the hyperglycemia-related prothrombotic phenotype. The mechanisms responsible for this phenomenon are not established. In the present study, we investigated the role of CD36, a class-B scavenger receptor, in this process. Using both in vitro and in vivo mouse models, we demonstrated direct and specific interactions of platelet CD36 with advanced glycation end products (AGEs) generated under hyperglycemic conditions. AGEs bound to platelet CD36 in a specific and dose-dependent manner, and binding was inhibited by the high-affinity CD36 ligand NO2LDL. Cd36-null platelets did not bind AGE. Using diet- and drug-induced mouse models of diabetes, we have shown that cd36-null mice had a delayed time to the formation of occlusive thrombi compared with wild-type (WT) in a FeCl3-induced carotid artery injury model. Cd36-null mice had a similar level of hyperglycemia and a similar level of plasma AGEs compared with WT mice under this condition, but WT mice had more AGEs incorporated into thrombi. Mechanistic studies revealed that CD36-dependent JNK2 activation is involved in this prothrombotic pathway. Therefore, the results of the present study couple vascular complications in diabetes mellitus with AGE-CD36–mediated platelet signaling and hyperreactivity.

Elevated endogenous secretory receptor for advanced glycation end products (esRAGE) levels are associated with circulating soluble RAGE levels in diabetic children

2017 ◽  
Vol 30 (1) ◽  
Author(s):  
Reiko Saito ◽  
Shunsuke Araki ◽  
Yukiyo Yamamoto ◽  
Koichi Kusuhara
Keyword(s):  
Advanced Glycation End Products ◽  
Vascular Complications ◽  
Soluble Form ◽  
Advanced Glycation ◽  
Diabetic Vascular Complications ◽  
Soluble Rage ◽  
Control Serum ◽  
Glycation End Products ◽  
End Products ◽  
Diabetic Children

AbstractBackground:Advanced glycation end products (AGEs) and the receptor for AGE (RAGE) play an important role in the development of diabetic vascular complications. This study aimed at investigating the relationship between the soluble form of RAGE (sRAGE), endogenous secretory RAGE (esRAGE), and pentosidine in childhood diabetes.Methods:The study included 18 children with type 1 diabetes mellitus (T1DM), 10 with type 2 DM (T2DM), and 22 age-matched, non-diabetic children (control).Results:Serum sRAGE levels in the T1DM (2557.7 pg/mL) were significantly higher than both T2DM (1956.4 pg/mL) and control (1658.5 pg/mL). The circulating levels of esRAGE in T1DM and T2DM children were similar, but significantly higher than those of control. Serum pentosidine levels in the T1DM group were positively correlated with serum sRAGE and esRAGE levels, but not with anthropometric or biochemical measurements. The duration of diabetes and esRAGE levels were independent predictors of the circulating sRAGE levels.Conclusions:Unlike adults, children with diabetes exhibit high circulating esRAGE levels, and both sRAGE and esRAGE levels are correlated with pentosidine levels. These results suggest that circulating sRAGE and esRAGE in children may be surrogate markers for progressive glucose toxicity in pediatric patients with childhood-onset diabetes.

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