Hidden Complexities in the Measurement of Fructosyl-Lysine and Advanced Glycation End Products for Risk Prediction of Vascular Complications of Diabetes

Rabbani, Naila; Thornalley, Paul J.

doi:10.2337/db14-1516

Cited by 19 publications

(10 citation statements)

References 21 publications

(20 reference statements)

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“…SA markedly increased the levels of fructoselysine, 1-methylguanosine, N -acetylhistamine, creatinine and L -isoleucine, D -glutamine, and citric acid compared to those in AMI mice. Some studies have shown that later-stage or advanced-stage glycation processes involve the degradation of fructoselysine and the glycation of proteins by methylglyoxal to form advanced glycation end products, which contribute to the pathogenesis of vascular complications of diabetes [ 24 ]. Additionally, 1-methylguanosine was identified as a marker that predicts the development of nephropathy in T2DM patients [ 25 ].…”

Section: Discussionmentioning

confidence: 99%

Exploring the protective effects of schizandrol A in acute myocardial ischemia mice by comprehensive metabolomics profiling integrated with molecular mechanism studies

et al. 2020

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Schizandrol A (SA) is an bioactive component isolated from the Schisandra chinensis (Turcz.) Baill., which has been used as a remedy to prevent oxidative injury. However, whether the cardioprotective effect of SA is associated with regulating endogenous metabolites remains unclear, thus we performed comprehensive metabolomics profiling in acute myocardial ischemia (AMI) mice following SA treatment. AMI was induced in ICR mice by coronary artery ligation, then SA (6 mg·kg −1 ·d −1 , ip) was administered. SA treatment significantly decreased the infarct size, preserved the cardiac function, and improved the biochemical indicators and cardiac pathological alterations. Moreover, SA (10, 100 M) significantly decreased the apoptotic index in OGD-treated H8c2 cardiomycytes in vitro. By using HPLC-Q-TOF/MS, we conducted metabonomics analysis to screen the significantly changed endogenous metabolites and construct the network in both serum and urine. The results revealed that SA regulated the pathways of glycine, serine and threonine metabolism, lysine biosynthesis, pyrimidine metabolism, arginine and proline metabolism, cysteine and methionine metabolism, valine, leucine and isoleucine biosynthesis under the pathological conditions of AMI. Furthermore, we selected the regulatory enzymes related to heart disease, including ecto-5’-nucleotidase (NT5E), guanidinoacetate N-methyltransferase (GAMT), platelet-derived endothelial cell growth factor (PD-ECGF) and methionine synthase (MTR), for validation. In addition, SA was found to facilitate PI3K/Akt activation and inhibit the expression of NOX2 in AMI mice and OGD-treated H9c2 cells. In conclusion, we have elucidated SA-regulated endogenous metabolic pathways and constructed a regulatory metabolic network map. Furthermore, we have validated the new potential therapeutic targets and underlying molecular mechanisms of SA against AMI, which might provide a reference for its future application in cardiovascular diseases.

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Section: Discussionmentioning

confidence: 99%

Exploring the protective effects of schizandrol A in acute myocardial ischemia mice by comprehensive metabolomics profiling integrated with molecular mechanism studies

et al. 2020

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“…This method is noninvasive, but is neither specific for individual AGEs, nor quantitative (38–41). Gas or LC-MS is sensitive, but not without technical limitations (23). Taken together, all of the issues in measurement make biologically meaningful assessment of AGE-related biomarkers difficult.…”

Section: Discussionmentioning

confidence: 99%

“…esRAGE has been studied less, although higher levels have been associated with an increased risk of major adverse cardiovascular events in people with diabetes (22). The variable findings for sRAGE have raised questions regarding its utility as a diabetes biomarker (23). Further complicating the field is that measurement of AGE products is challenging and methods have differed across studies.…”

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confidence: 99%

Cross-sectional Analysis of AGE-CML, sRAGE, and esRAGE with Diabetes and Cardiometabolic Risk Factors in a Community-Based Cohort

et al. 2017

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BACKGROUND Advanced glycation end products (AGEs) and their receptors are regarded as central to the development of diabetic complications, but associations with diabetes and cardiometabolic outcomes in previous studies are mixed. METHODS Using ELISA assays, we measured N(6)-carboxymethyllysine (AGE-CML), soluble receptor for AGEs (sRAGE), and endogenous secreted receptor for AGEs (esRAGE) in 1874 participants from the Atherosclerosis Risk in Communities study. We conducted a cross-sectional analysis to evaluate associations of these biomarkers with demographics, diabetes, hyperglycemia, cardiometabolic measures, and genetic variants in the gene encoding RAGE, AGER (advanced glycosylation end-product specific receptor). RESULTS After adjustment for demographics and body mass index (BMI), there were no significant differences in AGE-CML, sRAGE, or esRAGE by diabetes or hemoglobin A1c. Black race and AGER genetic variants were strongly associated with lower sRAGE and esRAGE even after adjustment [percent difference (95% CI) in black vs whites in sRAGE: −29.17 (−34.86 to −23.48), esRAGE: −26.97 (−33.11 to −20.84); with rs2070600 in sRAGE: −30.13 (−40.98 to −19.29), and esRAGE: −30.32 (−42.42 to −18.21); with rs2071288 in sRAGE: −20.03 (−34.87 to −5.18), and esRAGE: −37.70 (−55.75 to −19.65)]. Estimated glomerular filtration rate and albuminuria significantly correlated with sRAGE and esRAGE. BMI and C-reactive protein significantly negatively correlated with AGE-CML, sRAGE, and esRAGE. AGE-CML was modestly correlated with fructosamine and glycated albumin. CONCLUSIONS AGE-CML, sRAGE, and esRAGE were more related to genetic, kidney, and inflammatory measures than to diabetes in this community-based population. Our results suggest that, when measured by ELISA, these biomarkers lack specificity and are of limited value in evaluating the role of these compounds in diabetes.

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“…As shown in Figure 1,the adducts primarily result from a reaction between MGO and Nα-acetylarginine on the peptide backbone leading to an irreversible imidazolone derivative or hydroimidazolone (MG-H1) through autoxidation of an intermediate 1,5-dihydroimidazolone (Lo et al, 1994). Also, modification of the lysine residues triggered by MGO results in Nε-carboxyethyl-lysine (CEL) (Rabbani and Thornalley, 2015a). …”

Section: The Maillard Reaction: Initiators Propagators and Chemistrymentioning

confidence: 99%

The Role of Advanced Glycation End Products in Aging and Metabolic Diseases: Bridging Association and Causality

et al. 2018

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Accumulation of advanced glycation end products (AGEs) on nucleotides, lipids, and peptides/proteins are an inevitable component of the aging process in all eukaryotic organisms, including humans. To date, a substantial body of evidence shows that AGEs and their functionally compromised adducts are linked to and perhaps responsible for changes seen during aging and for the development of many age-related morbidities. However, much remains to be learned about the biology of AGE formation, causal nature of these associations, and whether new interventions might be developed that will prevent or reduce the negative impact of AGEs-related damage. To facilitate achieving these latter ends, we show how invertebrate models, notably Drosophila melanogaster and Caenorhabditis elegans, can be used to explore AGE-related pathways in depth and to identify and assess drugs that will mitigate against the detrimental effects of AGE-adduct development.

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Hidden Complexities in the Measurement of Fructosyl-Lysine and Advanced Glycation End Products for Risk Prediction of Vascular Complications of Diabetes

Cited by 19 publications

References 21 publications

Exploring the protective effects of schizandrol A in acute myocardial ischemia mice by comprehensive metabolomics profiling integrated with molecular mechanism studies

Exploring the protective effects of schizandrol A in acute myocardial ischemia mice by comprehensive metabolomics profiling integrated with molecular mechanism studies

Cross-sectional Analysis of AGE-CML, sRAGE, and esRAGE with Diabetes and Cardiometabolic Risk Factors in a Community-Based Cohort

The Role of Advanced Glycation End Products in Aging and Metabolic Diseases: Bridging Association and Causality

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