Elevated Serum Levels of Advanced Glycation End Products and their Monocyte Receptors in Patients with Type 2 Diabetes

Su, Xudong; Li, Shou-she; Tian, Yaqiang; Zhang, Zhao-yan; Zhang, Guangzhen; Wang, Lexin

doi:10.1016/j.arcmed.2011.11.001

Cited by 35 publications

(20 citation statements)

References 36 publications

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“…As reported by many studies [16,17], our study found decreased sRAGE level in PCD compared with healthy control. On the other hand, other studies [18,19] found higher level of sRAGE in T2DM compared with control subjects.…”

Section: Discussionsupporting

confidence: 88%

Effect of glycemic control on soluble RAGE and oxidative stress in type 2 diabetic patients

et al. 2013

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BackgroundThe interaction of advanced glycation end products (AGEs) and its receptor (RAGE) has played an important role in the pathogenesis of diabetes and its complications. A soluble form of RAGE (sRAGE) has been reported as a decoy receptor for AGEs. Oxidative stress is demonstrated in pathological condition such as atherosclerosis and diabetes mellitus. It has been suggested to be involved in the pathogenesis of both macro- and microvascular complications. This study was designed to evaluate the effect of glycemic control on sRAGE and oxidative stress markers in type 2 diabetic patients.MethodsSeventy patients with type 2 diabetes and 20 healthy subjects were recruited into the study. Blood glutathione (GSH) and plasma total nitric oxide (NOx) levels were measured using commercially available colorimetric kits, blood superoxide dismutase (SOD) activity was measured by the method of Marklund and Marklund, and plasma C-peptide, oxidized LDL (ox-LDL), sRAGE, and VCAM-1 levels were measured using competitive ELISA kits.ResultsPlasma sRAGE levels were significantly lower (p < 0.05) while VCAM-1 levels were significantly higher (p < 0.05) in poorly controlled diabetic patients compared with healthy control. Blood GSH levels were significantly lower in diabetic patients compared with healthy control (p < 0.05). Plasma C-peptide, NOx, ox-LDL levels, and SOD activity were not significantly different in diabetic patients compared with healthy control. Plasma levels of sRAGE were negatively associated with circulating VCAM-1 levels in diabetic patients.ConclusionPoor glycemic control decreases plasma sRAGE and increases VCAM-1 levels while good glycemic control improves these abnormalities which provides benefit to diabetic patients.

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Section: Discussionsupporting

confidence: 88%

Effect of glycemic control on soluble RAGE and oxidative stress in type 2 diabetic patients

et al. 2013

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“…24,27,30 Thus we anticipated that increased CD36 in DM2 could contribute to TB susceptibility in DM2 patients, but this was not observed. Finally, iv) RAGE is a scavenger receptor for glycated end products that is up-regulated in DM2 patients, and this receptor may play a role in TB pathogenesis, 27,31 but we did not find differences in RAGE expression between study groups. Despite the absence of differences in expression of CD11b, CD16, MHC-II, CD36 and RAGE in baseline blood monocytes of TB-DM versus TB-no DM, it is premature to rule out their contribution to TB susceptibility.…”

Section: Discussioncontrasting

confidence: 60%

Differential expression of monocyte surface markers among TB patients with diabetes co-morbidity

Stew¹,

Martinez²,

Schlesinger³

et al. 2013

Tuberculosis

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The expression of monocyte surface markers was compared between tuberculosis patients with and without type 2 diabetes (DM2). DM2 was associated with increased CCR2 expression, which may restrain monocyte traffic to the lung. Other host factors associated with baseline monocyte changes were older age (associated with lower CD11b) and obesity (associated with higher RAGE). Given that DM2 patients are more likely to be older and obese, their monocytes are predicted to be altered in function in ways that affect their interaction with Mycobacterium tuberculosis.

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“…Su and colleagues assessed AGER mRNA levels in monocytes from the peripheral blood of type 2 diabetic vs. non-diabetic human subjects (50 subjects per group). They reported a statistically-significant increase in levels of AGER in the diabetic vs. non-diabetic monocytes, which paralleled an increase in serum AGE levels and was inversely correlated with levels of soluble RAGE 54 . Tam and co-workers studied RAGE protein levels by Western blot in 53 diabetic and 52 control subjects and reported that monocyte full-length RAGE expression was significantly higher in the diabetic group but that a splice form of RAGE, called RAGEv1 or “endogenous secretory (es) RAGE” was lower.…”

Section: Rage and Signal Transductionmentioning

confidence: 90%

2016 ATVB Plenary Lecture

Schmidt

2017

ATVB

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The receptor for advanced glycation endproducts (RAGE) interacts with a unique repertoire of ligands that form and collect in the tissues and circulation in diabetes, aging, inflammation, renal failure and obesity. RAGE is expressed on multiple cell types linked to tissue perturbation in these settings. This Brief Review focuses on the role of RAGE in monocytes/macrophages and how RAGE ligand engagement on these cells mediates seminal changes in monocyte/macrophage migration, oxidative stress, cholesterol efflux and pro- vs. anti-inflammatory cues that signal to tissue damage. Studies using mice devoid of Ager (gene encoding RAGE) or pharmacological antagonists of RAGE are protective in animal models of diabetes, atherosclerosis, and high fat diet-induced obesity, in least in part through key roles in monocytes/macrophages. RAGE signal transduction requires the interaction of RAGE cytoplasmic domain with the formin, DIAPH1 and novel antagonists of this interaction show significant promise in attenuation of the maladaptive effects of RAGE ligands in cellular and in vivo models. Finally, this Brief Review discusses evidence for RAGE axis perturbation in human monocytes/macrophages and how tracing RAGE activity in these cells may identify target engagement biomarkers of RAGE antagonism for future clinical trials.

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Elevated Serum Levels of Advanced Glycation End Products and their Monocyte Receptors in Patients with Type 2 Diabetes

Cited by 35 publications

References 36 publications

Effect of glycemic control on soluble RAGE and oxidative stress in type 2 diabetic patients

Effect of glycemic control on soluble RAGE and oxidative stress in type 2 diabetic patients

Differential expression of monocyte surface markers among TB patients with diabetes co-morbidity

2016 ATVB Plenary Lecture

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