Theoretical studies on models of lysine-arginine cross-links derived from α-oxoaldehydes: a new mechanism for glucosepane formation

Nasiri, Rasoul; Zahedi, Mansour; Jamet, Hélène; Moosavi-Movahedi, Ali Akbar

doi:10.1007/s00894-011-1161-x

Cited by 10 publications

(9 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…3, implies a non-oxidative reaction initiated by FL reacting with an arginine residue via a so-called dideoxyglucosone intermediate. Very recently, an alternative, highly complex mechanism initiated by methylglyoxal, and followed by glyceraldehyde addition, was proposed based on computational calculations 28 . However, the role of this mechanism for GSPNE formation in diabetes is questionable since we were unable to find mass spectrometric evidence for in vivo formation of triosidines (unpublished data), i.e.…”

Section: Discussionmentioning

confidence: 99%

The association between skin collagen glucosepane and past progression of microvascular and neuropathic complications in type 1 diabetes

Monnier

Sell

Strauch

et al. 2013

Journal of Diabetes and its Complications

View full text Add to dashboard Cite

PURPOSE We determined the association between novel and acid-labile skin collagen-linked advanced glycation endproducts (AGEs) and the progression of microvascular and neuropathic complications from baseline to near study closeout in the Diabetes Control and Complications Trial (DCCT). METHODS From a skin biopsy obtained near the close of the DCCT, proteolytic collagen digests were analyzed by liquid chromatography/mass spectrometry (LC/MS/MS) for glucosepane (GSPNE), glyoxal and methylglyoxal hydroimidazolones (G-H1 and MG-H1) and the glycation product fructose-lysine(FL) using isotope dilution method. RESULTS GSPNE and MG-H1 correlated with age and diabetes duration (p<0.02), while GSPNE and FL correlated with the history of glycemia expressed as mean A1c(p≤0.003). Age and duration-adjusted GSPNE and FL levels were lower in intensive (INT) vs. conventional (CONV) treatment subjects in the primary prevention DCCT cohort (p < 0.0001), and FL lower in INT in the secondary intervention cohort (p < 0.0001). GSPNE was associated with increased incidence of retinopathy progression (odds ratio (OR)/unit increase in GSPNE: 2.5 for 3 step progression on the ETDRS scale, p=0.003) and sustained ≥ 3 microaneurysms (MA) (OR=4.8, p<0.0001) from DCCT baseline up to the time of the biopsy, and prevalence of microalbuminuria or AER>40 mg/24 hr (OR=5.3, P<0.0001), and confirmed clinical neuropathy (OR=3.4, p=0.015) at the time of the biopsy. GSPNE adjusted for mean A1c remained significant for ≥ 3 MA (p=0.0252) and AER (p=0.0006). The strong association of complications with A1c was reduced or eliminated when adjusted for GSPNE. CONCLUSIONS Glucosepane is a novel AGE marker of diabetic complications that is robustly associated with nephropathic, retinopathic and neuropathic outcomes despite adjustment for A1c, suggesting that it could be one mediator of these complications with possible diagnostic implications.

show abstract

Section: Discussionmentioning

confidence: 99%

The association between skin collagen glucosepane and past progression of microvascular and neuropathic complications in type 1 diabetes

Monnier

Sell

Strauch

et al. 2013

Journal of Diabetes and its Complications

View full text Add to dashboard Cite

show abstract

“…Thus, this form of carbonyl stress would proceed anaerobically in diabetes and be insensitive to antioxidants! Interestingly, Nasiri et al found, based on theoretical considerations, that glucosepane might possibly originate from a combination of methylglyoxal and glyceraldehyde [15]. In unpublished preliminary studies, we have found that glyceraldehyde, but not methylglyoxal, generates glucosepane-like m/z species in our LC/MS chromatogram.…”

Section: Glucosepane: Chemistry and Mechanism Of Formationmentioning

confidence: 48%

Glucosepane: a poorly understood advanced glycation end product of growing importance for diabetes and its complications

Monnier¹,

Sun

Sell

et al. 2014

Clinical Chemistry and Laboratory Medicine

View full text Add to dashboard Cite

Advanced glycation end products (AGEs) represent a family of protein, peptide, amino acid, nucleic acid and lipid adducts formed by the reaction of carbonyl compounds derived directly or indirectly from glucose, ascorbic acid and other metabolites such as methylglyoxal. AGE formation in diabetes is of growing importance for their role as markers and potential culprits of diabetic complications, in particular retinopathy, nephropathy and neuropathy. Development of sensitive and specific assays utilizing liquid chromatography mass spectrometry with isotope dilution method has made it possible to detect and quantitate non-UV active AGEs such as carboxymethyllysine and glucosepane, the most prevalent AGE and protein crosslink of the extracellular matrix. Below we review studies on AGE formation in two skin biopsies obtained near the closeout of the Diabetes Control and Complications Trial (DCCT), one of which was processed in 2011 for assay of novel AGEs. The results of these analyses show that while several AGEs are associated and predict complication progression, the glucose/fructose-lysine/glucosepane AGE axis is one of the most robust markers for microvascular disease, especially retinopathy, in spite of adjustment for past or future average glycemia. Yet overall little biological and clinical information is available on glucosepane, making this review a call for data in a field of growing importance for diabetes and chronic metabolic diseases of aging.

show abstract

“…28,61,[64][65][66][67] The reaction between these precursors and amino groups of proteins could happen either oxidatively or non-oxidatively, giving rise to different types of AGEs. The group of intermediate compounds produced during Amadori rearrangements, including the reactive carbonyl species (glyoxal, methylglyoxal and 3-deoxyglucosone) have been proposed to be the immediate precursors of AGEs.…”

Section: Advanced Glycation Endproducts (Ages)mentioning

confidence: 99%

“…The group of intermediate compounds produced during the Amadori rearrangements, including the reactive carbonyl species (glyoxal, methylglyoxal and 3-deoxyglucosone), have been proposed to be the immediate precursors of AGEs. 28,61,[64][65][66][67] The reaction between these precursors and the amino groups of proteins could happen either oxidatively or non-oxidatively, giving rise to different types of AGEs. 68 Carboxymethyllysine (CML) and pentosidine are two of the best Fig.…”

Section: Advanced Glycation End Products (Ages)mentioning

confidence: 99%

The colorants, antioxidants, and toxicants from nonenzymatic browning reactions and the impacts of dietary polyphenols on their thermal formation

et al. 2015

View full text Add to dashboard Cite

Nonenzymatic browning reactions proceed with the starting reactants of sugar and/or protein during thermal processing and storage of food. In addition to food color formation, the process also contributes to the loss of essential nutrients, generation of beneficial antioxidants, and production of toxicants, including 5-hydroxymethylfurfural (5-HMF), reactive carbonyl species, advanced glycation end products (AGEs), and heterocyclic amines (HAs). Recent research has demonstrated that dietary polyphenols can actively participate in nonenzymatic browning reactions, contributing to the generation of new colorants and antioxidants. More importantly, polyphenol addition has been found to be an effective approach to mitigate heat-induced formation of toxicants, mainly through inhibiting oxidative pathways and trapping reactive intermediates. In the matrix of polyphenol-fortified foods, a complex array of chemical interactions happen among polyphenols, traditional nutritional components, and neo-formed compounds they are thermally converted to. These reactions play a significant role in the colorants, antioxidants as well as toxicants production. Our findings support the potential of dietary polyphenols for increasing the antioxidant content and for reducing the level of toxicants when they participate in nonenzymatic browning reactions in fortified food products.

show abstract

Theoretical studies on models of lysine-arginine cross-links derived from α-oxoaldehydes: a new mechanism for glucosepane formation

Cited by 10 publications

References 55 publications

The association between skin collagen glucosepane and past progression of microvascular and neuropathic complications in type 1 diabetes

The association between skin collagen glucosepane and past progression of microvascular and neuropathic complications in type 1 diabetes

Glucosepane: a poorly understood advanced glycation end product of growing importance for diabetes and its complications

The colorants, antioxidants, and toxicants from nonenzymatic browning reactions and the impacts of dietary polyphenols on their thermal formation

Contact Info

Product

Resources

About