Dicarbonyls and Advanced Glycation End-Products in the Development of Diabetic Complications and Targets for Intervention

Advanced glycation end-products (AGEs) are non-enzymatic protein and amino acid adducts as well as DNA adducts which form from dicarbonyls and glucose. AGE formation is enhanced in diabetes and is associated with the development of diabetic complications. In the current review, we discuss mechanisms that lead to enhanced AGE levels in the context of diabetes and diabetic complications. The methylglyoxal-detoxifying glyoxalase system as well as alternative pathways of AGE detoxification are summarized. Therapeutic approaches to interfere with different pathways of AGE formation are presented.

[1]  K. Bennett,et al.  A Comprehensive Analytical Strategy To Identify Malondialdehyde-Modified Proteins and Peptides. , 2017, Analytical chemistry.

[2]  U. Haberkorn,et al.  A scavenger peptide prevents methylglyoxal induced pain in mice. , 2017, Biochimica et biophysica acta. Molecular basis of disease.

[3]  M. Freichel,et al.  Loss of Glyoxalase 1 Induces Compensatory Mechanism to Achieve Dicarbonyl Detoxification in Mammalian Schwann Cells* , 2016, The Journal of Biological Chemistry.

[4]  T. Lauritzen,et al.  Methylglyoxal is associated with changes in kidney function among individuals with screen‐detected Type 2 diabetes mellitus , 2016, Diabetic medicine : a journal of the British Diabetic Association.

[5]  Paul J Thornalley,et al.  Mass spectrometric determination of early and advanced glycation in biology , 2016, Glycoconjugate Journal.

[6]  Paul J Thornalley,et al.  Dicarbonyls and glyoxalase in disease mechanisms and clinical therapeutics , 2016, Glycoconjugate Journal.

[7]  J. Forbes,et al.  Targeting advanced glycation with pharmaceutical agents: where are we now? , 2016, Glycoconjugate Journal.

[8]  S. Genuth,et al.  The pecking order of skin Advanced Glycation Endproducts (AGEs) as long-term markers of glycemic damage and risk factors for micro- and subclinical macrovascular disease progression in Type 1 diabetes , 2016, Glycoconjugate Journal.

[9]  M. Glomb,et al.  Pathways of the Maillard reaction under physiological conditions , 2016, Glycoconjugate Journal.

[10]  Paul J Thornalley,et al.  Improved Glycemic Control and Vascular Function in Overweight and Obese Subjects by Glyoxalase 1 Inducer Formulation , 2016, Diabetes.

[11]  S. Snyder,et al.  Metformin Scavenges Methylglyoxal To Form a Novel Imidazolinone Metabolite in Humans. , 2016, Chemical research in toxicology.

[12]  M. Pischetsrieder,et al.  Quantification of reactive carbonyl compounds in icodextrin-based peritoneal dialysis fluids by combined UHPLC-DAD and -MS/MS detection. , 2016, Journal of pharmaceutical and biomedical analysis.

[13]  C. Drăghici,et al.  Concise total synthesis of glucosepane , 2015, Science.

[14]  G. Cooper,et al.  Diabetes-induced alterations in tissue collagen and carboxymethyllysine in rat kidneys: Association with increased collagen-degrading proteinases and amelioration by Cu(II)-selective chelation. , 2015, Biochimica et Biophysica Acta.

[15]  T. Lauritzen,et al.  The role of serum methylglyoxal on diabetic peripheral and cardiovascular autonomic neuropathy: the ADDITION Denmark study , 2015, Diabetic medicine : a journal of the British Diabetic Association.

[16]  R. Nagaraj,et al.  Comprehensive analysis of maillard protein modifications in human lenses: effect of age and cataract. , 2015, Biochemistry.

[17]  Paul J Thornalley,et al.  Increased DNA Dicarbonyl Glycation and Oxidation Markers in Patients with Type 2 Diabetes and Link to Diabetic Nephropathy , 2015, Journal of diabetes research.

[18]  Rico Schmidt,et al.  Specific tandem mass spectrometric detection of AGE-modified arginine residues in peptides. , 2015, Journal of mass spectrometry : JMS.

[19]  H. Daniel,et al.  Glyoxylate, a New Marker Metabolite of Type 2 Diabetes , 2014, Journal of diabetes research.

[20]  S. Genuth,et al.  Skin Advanced Glycation End Products Glucosepane and Methylglyoxal Hydroimidazolone Are Independently Associated With Long-term Microvascular Complication Progression of Type 1 Diabetes , 2014, Diabetes.

[21]  M. Glomb,et al.  Extending the Spectrum of α-Dicarbonyl Compounds in Vivo* , 2014, The Journal of Biological Chemistry.

[22]  Paul J Thornalley,et al.  Measurement of methylglyoxal by stable isotopic dilution analysis LC-MS/MS with corroborative prediction in physiological samples , 2014, Nature Protocols.

[23]  Q. Su,et al.  Increased plasma levels of the methylglyoxal in patients with newly diagnosed type 2 diabetes 初诊2型糖尿病患者血浆甲基乙二醛水平升高 , 2014, Journal of diabetes.

[24]  Stephan Herzig,et al.  Effect of metformin on methylglyoxal metabolism in patients with type 2 diabetes. , 2014, Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association.

[25]  Paul J Thornalley,et al.  Dicarbonyl proteome and genome damage in metabolic and vascular disease. , 2014, Biochemical Society transactions.

[26]  M. Hellwig,et al.  Dietary influence on urinary excretion of 3-deoxyglucosone and its metabolite 3-deoxyfructose. , 2014, Journal of agricultural and food chemistry.

[27]  Paul J Thornalley,et al.  Detection of oxidized and glycated proteins in clinical samples using mass spectrometry--a user's perspective. , 2014, Biochimica et biophysica acta.

[28]  G. Lamas,et al.  The Effect of an EDTA-based Chelation Regimen on Patients With Diabetes Mellitus and Prior Myocardial Infarction in the Trial to Assess Chelation Therapy (TACT) , 2014, Circulation. Cardiovascular quality and outcomes.

[29]  V. D’Agati,et al.  Knockdown of Glyoxalase 1 Mimics Diabetic Nephropathy in Nondiabetic Mice , 2013, Diabetes.

[30]  C. Stehouwer,et al.  Plasma levels of advanced glycation endproducts are associated with type 1 diabetes and coronary artery calcification , 2013, Cardiovascular Diabetology.

[31]  Michael E. Miller,et al.  Early Progression of Diabetic Nephropathy Correlates With Methylglyoxal-Derived Advanced Glycation End Products , 2013, Diabetes Care.

[32]  António E. N. Ferreira,et al.  The glyoxalase pathway: the first hundred years... and beyond. , 2013, The Biochemical journal.

[33]  N. Žarković,et al.  Advanced glycoxidation and lipoxidation end products (AGEs and ALEs): an overview of their mechanisms of formation , 2013, Free radical research.

[34]  H. Parving,et al.  The methylglyoxal-derived AGE tetrahydropyrimidine is increased in plasma of individuals with type 1 diabetes mellitus and in atherosclerotic lesions and is associated with sVCAM-1 , 2013, Diabetologia.

[35]  M. Glomb,et al.  Maillard degradation pathways of vitamin C. , 2013, Angewandte Chemie.

[36]  G. Lamas,et al.  Effect of disodium EDTA chelation regimen on cardiovascular events in patients with previous myocardial infarction: the TACT randomized trial. , 2013, JAMA.

[37]  M. Hellwig,et al.  Metabolic transit of dietary methylglyoxal. , 2013, Journal of agricultural and food chemistry.

[38]  M. Kalapos.  Where does plasma methylglyoxal originate from? , 2013, Diabetes research and clinical practice.

[39]  R. Wender,et al.  Erratum to: Management of hyperglycaemia in type 2 diabetes: a patient-centered approach. Position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) , 2013, Diabetologia.

[40]  D. Spiegel,et al.  The unique reactivity of N-phenacyl-derived thiazolium salts toward α-dicarbonyl compounds. , 2013, Rejuvenation research.

[41]  G. Striker,et al.  Oral advanced glycation endproducts (AGEs) promote insulin resistance and diabetes by depleting the antioxidant defenses AGE receptor-1 and sirtuin 1 , 2012, Proceedings of the National Academy of Sciences.

[42]  Paul J Thornalley,et al.  Methylglyoxal modification of Nav1.8 facilitates nociceptive neuron firing and causes hyperalgesia in diabetic neuropathy , 2012, Nature Medicine.

[43]  C. Kahn,et al.  Retinaldehyde dehydrogenase 1 regulates a thermogenic program in white adipose tissue , 2012, Nature Medicine.

[44]  Paul J Thornalley,et al.  Transcriptional control of glyoxalase 1 by Nrf2 provides a stress-responsive defence against dicarbonyl glycation. , 2012, The Biochemical journal.

[45]  T. Reinheckel,et al.  Cathepsins D and L reduce the toxicity of advanced glycation end products. , 2012, Free radical biology & medicine.

[46]  T. Metz,et al.  Chelation: A Fundamental Mechanism of Action of AGE Inhibitors, AGE Breakers, and Other Inhibitors of Diabetes Complications , 2012, Diabetes.

[47]  J. Handa,et al.  Glycation‐altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age‐related disease (in nondiabetics) , 2012, Aging cell.

[48]  M. Zeier,et al.  Is diabetes an acquired disorder of reactive glucose metabolites and their intermediates? , 2012, Diabetologia.

[49]  M. Sano,et al.  Serum concentration of an inflammatory glycotoxin, methylglyoxal, is associated with increased cognitive decline in elderly individuals , 2011, Mechanisms of Ageing and Development.

[50]  G. Striker,et al.  Restriction of Advanced Glycation End Products Improves Insulin Resistance in Human Type 2 Diabetes , 2011, Diabetes Care.

[51]  Paul J Thornalley,et al.  Glyoxalase in diabetes, obesity and related disorders. , 2011, Seminars in cell & developmental biology.

[52]  K. Adeli,et al.  Increased plasma methylglyoxal level, inflammation, and vascular endothelial dysfunction in diabetic nephropathy. , 2011, Clinical biochemistry.

[53]  H. Parving,et al.  Higher Plasma Levels of Advanced Glycation End Products Are Associated With Incident Cardiovascular Disease and All-Cause Mortality in Type 1 Diabetes , 2011, Diabetes Care.

[54]  M. Glomb,et al.  Formation of arginine modifications in a model system of Nα-tert-butoxycarbonyl (Boc)-arginine with methylglyoxal. , 2011, Journal of agricultural and food chemistry.

[55]  Lingyun Wu,et al.  Methylglyoxal scavengers attenuate endothelial dysfunction induced by methylglyoxal and high concentrations of glucose , 2010, British journal of pharmacology.

[56]  S. Ito,et al.  Methylglyoxal Is a Predictor in Type 2 Diabetic Patients of Intima-Media Thickening and Elevation of Blood Pressure , 2010, Hypertension.

[57]  M. Stratton,et al.  Imidazopurinones are markers of physiological genomic damage linked to DNA instability and glyoxalase 1-associated tumour multidrug resistance , 2010, Nucleic acids research.

[58]  J. Baynes,et al.  Citric acid inhibits development of cataracts, proteinuria and ketosis in streptozotocin (type 1) diabetic rats. , 2010, Biochemical and biophysical research communications.

[59]  K. Nair,et al.  Protein and energy metabolism in type 1 diabetes. , 2010, Clinical nutrition.

[60]  Lingyun Wu,et al.  Alagebrium attenuates acute methylglyoxal‐induced glucose intolerance in Sprague‐Dawley rats , 2010, British journal of pharmacology.

[61]  Paul J Thornalley,et al.  Advanced Glycation End Products in Extracellular Matrix Proteins Contribute to the Failure of Sensory Nerve Regeneration in Diabetes , 2009, Diabetes.

[62]  A. Bhatnagar,et al.  Reductive Metabolism of AGE Precursors: A Metabolic Route for Preventing AGE Accumulation in Cardiovascular Tissue , 2009, Diabetes.

[63]  J. Donoso,et al.  A comparative study of the chemical reactivity of pyridoxamine, Ac-Phe-Lys and Ac-Cys with various glycating carbonyl compounds , 2009, Amino Acids.

[64]  R. Doughty,et al.  A copper(II)-selective chelator ameliorates left-ventricular hypertrophy in type 2 diabetic patients: a randomised placebo-controlled study , 2009, Diabetologia.

[65]  J. Termini,et al.  Advanced glycation end products of DNA: quantification of N2-(1-Carboxyethyl)-2'-deoxyguanosine in biological samples by liquid chromatography electrospray ionization tandem mass spectrometry. , 2008, Chemical research in toxicology.

[66]  M. Pischetsrieder,et al.  Analysis and biological relevance of advanced glycation end‐products of DNA in eukaryotic cells , 2008, The FEBS journal.

[67]  L. Cai,et al.  The Role of Zinc, Copper and Iron in the Pathogenesis of Diabetes and Diabetic Complications: Therapeutic Effects by Chelators , 2008, Hemoglobin.

[68]  I. Mahmood.  Application of allometric principles for the prediction of pharmacokinetics in human and veterinary drug development. , 2007, Advanced drug delivery reviews.

[69]  Mark E. Williams,et al.  Effects of Pyridoxamine in Combined Phase 2 Studies of Patients with Type 1 and Type 2 Diabetes and Overt Nephropathy , 2007, American Journal of Nephrology.

[70]  R. Ramasamy,et al.  Arguing for the motion: yes, RAGE is a receptor for advanced glycation endproducts. , 2007, Molecular nutrition & food research.

[71]  C. Heizmann.  The mechanism by which dietary AGEs are a risk to human health is via their interaction with RAGE: arguing against the motion. , 2007, Molecular nutrition & food research.

[72]  T. Niwa,et al.  Pyridoxal phosphate prevents progression of diabetic nephropathy. , 2007, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[73]  E. Randell,et al.  Plasma methylglyoxal and glyoxal are elevated and related to early membrane alteration in young, complication-free patients with Type 1 diabetes , 2007, Molecular and Cellular Biochemistry.

[74]  Paul J Thornalley,et al.  Advanced glycation endproducts: what is their relevance to diabetic complications? , 2007, Diabetes, obesity & metabolism.

[75]  D. Vertommen,et al.  Identification of 3-deoxyglucosone dehydrogenase as aldehyde dehydrogenase 1A1 (retinaldehyde dehydrogenase 1). , 2007, Biochimie.

[76]  Y. Tomino,et al.  Effect of pyridoxamine (K-163), an inhibitor of advanced glycation end products, on type 2 diabetic nephropathy in KK-A(y)/Ta mice. , 2007, Metabolism: clinical and experimental.

[77]  D. Vertommen,et al.  Increased protein glycation in fructosamine 3-kinase-deficient mice. , 2006, The Biochemical journal.

[78]  R. Nagaraj,et al.  Upregulation of Glyoxalase I fails to Normalize Methylglyoxal Levels: A Possible Mechanism for Biochemical Changes in Diabetic Mouse Lenses , 2006, Molecular and Cellular Biochemistry.

[79]  T. Niwa,et al.  N2-carboxyethyl-2'-deoxyguanosine, a DNA glycation marker, in kidneys and aortas of diabetic and uremic patients. , 2006, Kidney international.

[80]  R. Nelson,et al.  Susceptibility to diabetic nephropathy is related to dicarbonyl and oxidative stress. , 2005, Diabetes.

[81]  S. Genuth,et al.  Glycation and carboxymethyllysine levels in skin collagen predict the risk of future 10-year progression of diabetic retinopathy and nephropathy in the diabetes control and complications trial and epidemiology of diabetes interventions and complications participants with type 1 diabetes. , 2005, Diabetes.

[82]  J. Angerer,et al.  Identification of DNA adducts of methylglyoxal. , 2005, Chemical research in toxicology.

[83]  Paul J Thornalley,et al.  Degradation products of proteins damaged by glycation, oxidation and nitration in clinical type 1 diabetes , 2005, Diabetologia.

[84]  Paul J Thornalley,et al.  Peptide Mapping of Human Serum Albumin Modified Minimally by Methylglyoxal in Vitro and in Vivo , 2005, Annals of the New York Academy of Sciences.

[85]  S. Horiuchi,et al.  Conventional antibody against Nε-(carboxymethyl)lysine (CML) shows cross-reaction to Nε-(carboxyethyl)lysine (CEL): Immunochemical quantification of CML with a specific antibody , 2004 .

[86]  M. Cooper,et al.  Attenuation of extracellular matrix accumulation in diabetic nephropathy by the advanced glycation end product cross-link breaker ALT-711 via a protein kinase C-alpha-dependent pathway. , 2004, Diabetes.

[87]  P. Ståhl,et al.  Determination of glycated nucleobases in human urine by a new monoclonal antibody specific for N2-carboxyethyl-2'-deoxyguanosine. , 2004, Chemical research in toxicology.

[88]  R. Gans,et al.  Simple non-invasive assessment of advanced glycation endproduct accumulation , 2004, Diabetologia.

[89]  C. Schalkwijk,et al.  Measurement of Nε-(Carboxymethyl)lysine and Nε-(Carboxyethyl)lysine in Human Plasma Protein by Stable-Isotope-Dilution Tandem Mass Spectrometry , 2004 .

[90]  Mark E. Williams,et al.  Randomized Trial of an Inhibitor of Formation of Advanced Glycation End Products in Diabetic Nephropathy , 2004, American Journal of Nephrology.

[91]  D. Slatter,et al.  Identification of a New Cross-link and Unique Histidine Adduct from Bovine Serum Albumin Incubated with Malondialdehyde* , 2004, Journal of Biological Chemistry.

[92]  E. Schaftingen,et al.  Fructosamine 3-kinase, an enzyme involved in protein deglycation. , 2003, Biochemical Society transactions.

[93]  Paul J Thornalley,et al.  Accumulation of fructosyl-lysine and advanced glycation end products in the kidney, retina and peripheral nerve of streptozotocin-induced diabetic rats. , 2003, Biochemical Society transactions.

[94]  Paul J Thornalley.  Glyoxalase I--structure, function and a critical role in the enzymatic defence against glycation. , 2003, Biochemical Society transactions.

[95]  R. Khalifah,et al.  Modification of Proteins In Vitro by Physiological Levels of Glucose , 2003, Journal of Biological Chemistry.

[96]  Anne Dawnay,et al.  Quantitative screening of advanced glycation endproducts in cellular and extracellular proteins by tandem mass spectrometry. , 2003, The Biochemical journal.

[97]  L. A. Hunsaker,et al.  Aldo-Keto Reductase-Catalyzed Detoxication of Endogenous Aldehydes Associated with Diabetic Complications , 2003 .

[98]  T. Penning,et al.  Aldo-keto reductases and toxicant metabolism , 2003 .

[99]  M. Kasuga,et al.  Relation between serum 3-deoxyglucosone and development of diabetic microangiopathy. , 2003, Diabetes care.

[100]  J. Baynes,et al.  AGE-breakers cleave model compounds, but do not break Maillard crosslinks in skin and tail collagen from diabetic rats. , 2003, Archives of biochemistry and biophysics.

[101]  P. Traldi,et al.  Glyoxal and Methylglyoxal Levels in Diabetic Patients: Quantitative Determination by a New GC/MS Method , 2003, Clinical chemistry and laboratory medicine.

[102]  J. Baynes,et al.  CML: a brief history , 2002 .

[103]  N. Ahmed,et al.  Kinetics and mechanism of the reaction of metformin with methylglyoxal , 2002 .

[104]  Alan W. Stitt,et al.  The AGE inhibitor pyridoxamine inhibits development of retinopathy in experimental diabetes. , 2002, Diabetes.

[105]  K. Biemel,et al.  Identification and Quantification of Major Maillard Cross-links in Human Serum Albumin and Lens Protein , 2002, The Journal of Biological Chemistry.

[106]  R. Nagaraj,et al.  Effect of pyridoxamine on chemical modification of proteins by carbonyls in diabetic rats: characterization of a major product from the reaction of pyridoxamine and methylglyoxal. , 2002, Archives of biochemistry and biophysics.

[107]  Paul J Thornalley,et al.  Assay of advanced glycation endproducts (AGEs): surveying AGEs by chromatographic assay with derivatization by 6-aminoquinolyl-N-hydroxysuccinimidyl-carbamate and application to Nepsilon-carboxymethyl-lysine- and Nepsilon-(1-carboxyethyl)lysine-modified albumin. , 2002, The Biochemical journal.

[108]  K. Biemel,et al.  Unexpected carbonyl mobility in aminoketoses: the key to major Maillard crosslinks. , 2002, Angewandte Chemie.

[109]  M. Steffes,et al.  Pyridoxamine inhibits early renal disease and dyslipidemia in the streptozotocin-diabetic rat. , 2002, Kidney international.

[110]  T. Metz,et al.  A Post-Amadori Inhibitor Pyridoxamine Also Inhibits Chemical Modification of Proteins by Scavenging Carbonyl Intermediates of Carbohydrate and Lipid Degradation* , 2002, The Journal of Biological Chemistry.

[111]  B. Szwergold,et al.  Human fructosamine-3-kinase: purification, sequencing, substrate specificity, and evidence of activity in vivo. , 2001, Diabetes.

[112]  K. Biemel,et al.  Formation Pathways for Lysine-Arginine Cross-links Derived from Hexoses and Pentoses by Maillard Processes , 2001, The Journal of Biological Chemistry.

[113]  M. Cotter,et al.  Effects of an extracellular metal chelator on neurovascular function in diabetic rats , 2001, Diabetologia.

[114]  D. V. Vander Jagt,et al.  Metabolism of the 2-oxoaldehyde methylglyoxal by aldose reductase and by glyoxalase-I: roles for glutathione in both enzymes and implications for diabetic complications. , 2001, Chemico-biological interactions.

[115]  J. Bijlsma,et al.  Effect of Collagen Turnover on the Accumulation of Advanced Glycation End Products* , 2000, The Journal of Biological Chemistry.

[116]  Paul J Thornalley,et al.  Kinetics and mechanism of the reaction of aminoguanidine with the alpha-oxoaldehydes glyoxal, methylglyoxal, and 3-deoxyglucosone under physiological conditions. , 2000, Biochemical pharmacology.

[117]  D. Slatter,et al.  The importance of lipid-derived malondialdehyde in diabetes mellitus , 2000, Diabetologia.

[118]  P. Delmas,et al.  Racemization and isomerization of type I collagen C-telopeptides in human bone and soft tissues: assessment of tissue turnover. , 2000, The Biochemical journal.

[119]  R. Schinzel,et al.  N(2)-(1-Carboxyethyl)deoxyguanosine, a nonenzymatic glycation adduct of DNA, induces single-strand breaks and increases mutation frequencies. , 1999, Biochemical and biophysical research communications.

[120]  R. Bain,et al.  Design and baseline characteristics for the aminoguanidine Clinical Trial in Overt Type 2 Diabetic Nephropathy (ACTION II). , 1999, Controlled clinical trials.

[121]  K. Maeda,et al.  Increase in Three α,β-Dicarbonyl Compound Levels in Human Uremic Plasma: Specificin VivoDetermination of Intermediates in Advanced Maillard Reaction , 1999 .

[122]  R. Neidlein,et al.  Aminoguanidine inhibits albuminuria, but not the formation of advanced glycation end-products in skin collagen of diabetic rats. , 1999, Diabetes research and clinical practice.

[123]  M. Huijberts,et al.  Breakers of advanced glycation end products restore large artery properties in experimental diabetes. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[124]  N. Taniguchi,et al.  Overexpression of aldehyde reductase protects PC12 cells from the cytotoxicity of methylglyoxal or 3-deoxyglucosone. , 1998, Journal of biochemistry.

[125]  G. Jerums,et al.  Relative contributions of advanced glycation and nitric oxide synthase inhibition to aminoguanidine-mediated renoprotection in diabetic rats , 1997, Diabetologia.

[126]  A. Jenkins,et al.  Quantification of malondialdehyde and 4-hydroxynonenal adducts to lysine residues in native and oxidized human low-density lipoprotein. , 1997, The Biochemical journal.

[127]  J. Nyengaard,et al.  Discordant Effects of Guanidines on Renal Structure and Function and on Regional Vascular Dysfunction and Collagen Changes in Diabetic Rats , 1997, Diabetes.

[128]  M. A. Bowman,et al.  Pharmacokinetics of aminoguanidine administration and effects on the diabetes frequency in nonobese diabetic mice. , 1996, The Journal of pharmacology and experimental therapeutics.

[129]  J. Bernhagen,et al.  An agent cleaving glucose-derived protein crosslinks in vitro and in vivo , 1996, Nature.

[130]  T. Lyons,et al.  The Advanced Glycation End Product, N-(Carboxymethyl)lysine, Is a Product of both Lipid Peroxidation and Glycoxidation Reactions (*) , 1996, The Journal of Biological Chemistry.

[131]  G. Spiteller,et al.  Previously unknown aldehydic lipid peroxidation compounds of arachidonic acid. , 1996, Chemistry and physics of lipids.

[132]  J. Baynes,et al.  Pathways of formation of glycoxidation products during glycation of collagen. , 1995, Biochemistry.

[133]  M. Cotter,et al.  Neurovascular dysfunction in diabetic rats. Potential contribution of autoxidation and free radicals examined using transition metal chelating agents. , 1995, The Journal of clinical investigation.

[134]  E. Fujii,et al.  The presence of 2-keto-3-deoxygluconic acid and oxoaldehyde dehydrogenase activity in human erythrocytes. , 1995, Biochemical and biophysical research communications.

[135]  V. Monnier,et al.  Mechanism of Protein Modification by Glyoxal and Glycolaldehyde, Reactive Intermediates of the Maillard Reaction (*) , 1995, The Journal of Biological Chemistry.

[136]  J. Baynes,et al.  Mechanism of autoxidative glycosylation: identification of glyoxal and arabinose as intermediates in the autoxidative modification of proteins by glucose. , 1995, Biochemistry.

[137]  Paul J Thornalley,et al.  Binding and modification of proteins by methylglyoxal under physiological conditions. A kinetic and mechanistic study with N alpha-acetylarginine, N alpha-acetylcysteine, and N alpha-acetyllysine, and bovine serum albumin. , 1994, The Journal of biological chemistry.

[138]  T. Lyons,et al.  3-Deoxyfructose Concentrations are Increased in Human Plasma and Urine in Diabetes , 1994, Diabetes.

[139]  Paul J Thornalley,et al.  Glyoxalase system in clinical diabetes mellitus and correlation with diabetic complications. , 1994, Clinical science.

[140]  J. V. Hunt,et al.  Oxidative alterations in the experimental glycation model of diabetes mellitus are due to protein-glucose adduct oxidation. Some fundamental differences in proposed mechanisms of glucose oxidation and oxidant production. , 1993, The Biochemical journal.

[141]  Paul J Thornalley,et al.  The formation of methylglyoxal from triose phosphates , 1993 .

[142]  Paul J Thornalley,et al.  The assay of methylglyoxal in biological systems by derivatization with 1,2-diamino-4,5-dimethoxybenzene. , 1992, Analytical biochemistry.

[143]  M. Mcdaniel,et al.  Aminoguanidine, a Novel Inhibitor of Nitric Oxide Formation, Prevents Diabetic Vascular Dysfunction , 1992, Diabetes.

[144]  H. Hammes,et al.  Aminoguanidine treatment inhibits the development of experimental diabetic retinopathy , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[145]  T. Lyons,et al.  Age-dependent accumulation of N epsilon-(carboxymethyl)lysine and N epsilon-(carboxymethyl)hydroxylysine in human skin collagen. , 1991, Biochemistry.

[146]  J. Richardson,et al.  Reaction of ascorbate with lysine and protein under autoxidizing conditions: formation of N epsilon-(carboxymethyl)lysine by reaction between lysine and products of autoxidation of ascorbate. , 1990, Biochemistry.

[147]  H. Kato,et al.  Metabolism of 3-deoxyglucosone, an intermediate compound in the Maillard reaction, administered orally or intravenously to rats. , 1990, Biochimica et biophysica acta.

[148]  T. Brown,et al.  Identification of fructose 3-phosphate in the lens of diabetic rats. , 1990, Science.

[149]  V. Monnier,et al.  Structure elucidation of a senescence cross-link from human extracellular matrix. Implication of pentoses in the aging process. , 1989, The Journal of biological chemistry.

[150]  J. Baynes,et al.  Oxidative degradation of glucose adducts to protein. Formation of 3-(N epsilon-lysino)-lactic acid from model compounds and glycated proteins. , 1988, The Journal of biological chemistry.

[151]  C. Hasslacher,et al.  Degradation of glomerular basement membrane in diabetes , 1987, Research in experimental medicine. Zeitschrift fur die gesamte experimentelle Medizin einschliesslich experimenteller Chirurgie.

[152]  S P Wolff,et al.  Glucose autoxidation and protein modification. The potential role of 'autoxidative glycosylation' in diabetes. , 1987, The Biochemical journal.

[153]  R. Flückiger,et al.  Nonenzymatic glycosylation of albumin in vivo. Identification of multiple glycosylated sites. , 1986, The Journal of biological chemistry.

[154]  A. Cerami,et al.  Aminoguanidine prevents diabetes-induced arterial wall protein cross-linking. , 1986, Science.

[155]  J. Baynes,et al.  Identification of N epsilon-carboxymethyllysine as a degradation product of fructoselysine in glycated protein. , 1986, The Journal of biological chemistry.

[156]  M. Namiki,et al.  Formation of Two-Carbon Sugar Fragment at an Early Stage of the Browning Reaction of Sugar with Amine , 1980 .

[157]  D. V. Vander Jagt,et al.  Effects of pH and thiols on the kinetics of yeast glyoxalase I. An evaluation of the random pathway mechanism. , 1975, Biochemistry.

[158]  S. Lyons,et al.  The effect of streptozotocin diabetes on the levels of glycolate and lactate excreted in rat urine. , 1975, Archives of biochemistry and biophysics.

[159]  S. K. Wadman,et al.  Nϵ-(carboxymethyd)lysine, a constituent of human urine , 1975 .

[160]  D. V. Vander Jagt,et al.  Kinetic evaluation of substrate specificity in the glyoxalase-I-catalyzed disproportionation of -ketoaldehydes. , 1972, Biochemistry.

[161]  R. E. Neuman,et al.  The determination of collagen and elastin in tissues. , 1950, The Journal of biological chemistry.

[162]  C. Schalkwijk,et al.  Quantification of glyoxal, methylglyoxal and 3-deoxyglucosone in blood and plasma by ultra performance liquid chromatography tandem mass spectrometry: evaluation of blood specimen , 2014, Clinical chemistry and laboratory medicine.

[163]  M. Cooper,et al.  Mechanisms of diabetic complications. , 2013, Physiological reviews.

[164]  C. Stehouwer,et al.  Glyoxalase-1 overexpression reduces endothelial dysfunction and attenuates early renal impairment in a rat model of diabetes , 2013, Diabetologia.

[165]  Morten Wang Fagerland,et al.  Associations with glycemic control and advanced protein glycation: The Oslo Study , 2013 .

[166]  E. Lewis,et al.  Pyridorin in type 2 diabetic nephropathy. , 2012, Journal of the American Society of Nephrology : JASN.

[167]  D. V. Vander Jagt.  Methylglyoxal, diabetes mellitus and diabetic complications. , 2008, Drug metabolism and drug interactions.

[168]  B. Szwergold.  Fructosamine-6-phosphates are deglycated by phosphorylation to fructosamine-3,6-bisphosphates catalyzed by fructosamine-3-kinase (FN3K) and/or fructosamine-3-kinase-related-protein (FN3KRP). , 2007, Medical hypotheses.

[169]  K. Uchida,et al.  Mass spectroscopic characterization of protein modification by malondialdehyde. , 2006, Chemical research in toxicology.

[170]  T. Hughes,et al.  Advanced glycation end product ligands for the receptor for advanced glycation end products: biochemical characterization and formation kinetics. , 2004, Analytical biochemistry.

[171]  B. Szwergold,et al.  Metformin reduces systemic methylglyoxal levels in type 2 diabetes. , 1999, Diabetes.

[172]  J. Richardson,et al.  Formation of reactive intermediates from Amadori compounds under physiological conditions. , 1995, Archives of biochemistry and biophysics.

[173]  Paul J Thornalley,et al.  The formation of methylglyoxal from triose phosphates. Investigation using a specific assay for methylglyoxal. , 1993, European journal of biochemistry.

[174]  P. Thornalley,et al.  S-2-hydroxyacylglutathione-derivatives: enzymatic preparation, purification and characterisation , 1991 .

[175]  Paul J Thornalley,et al.  The human red blood cell glyoxalase system in diabetes mellitus. , 1989, Diabetes research and clinical practice.

[176]  L. Maillard,et al.  Action des acides amines sur les sucres : formation des melanoidines par voie methodique , 1912 .