Heart Failure Reviews

, Volume 19, Issue 1, pp 49–63

Advanced glycation end products: role in pathology of diabetic cardiomyopathy

  • Vijaya Lakshmi Bodiga
  • Sasidhar Reddy Eda
  • Sreedhar Bodiga


Increasing evidence demonstrates that advanced glycation end products (AGEs) play a pivotal role in the development and progression of diabetic heart failure, although there are numerous other factors that mediate the disease response. AGEs are generated intra- and extracellularly as a result of chronic hyperglycemia. Then, following the interaction with receptors for advanced glycation end products (RAGEs), a series of events leading to vascular and myocardial damage are elicited and sustained, which include oxidative stress, increased inflammation, and enhanced extracellular matrix accumulation resulting in diastolic and systolic dysfunction. Whereas targeting glycemic control and treating additional risk factors, such as obesity, dyslipidemia, and hypertension, are mandatory to reduce chronic complications and prolong life expectancy in diabetic patients, drug therapy tailored to reducing the deleterious effects of the AGE–RAGE interactions is being actively investigated and showing signs of promise in treating diabetic cardiomyopathy and associated heart failure. This review shall discuss the formation of AGEs in diabetic heart tissue, potential targets of glycation in the myocardium, and underlying mechanisms that lead to diabetic cardiomyopathy and heart failure along with the use of AGE inhibitors and breakers in mitigating myocardial injury.


Glycation Diabetes Cardiomyopathy Advanced glycation end products RAGE Heart failure AGE breakers 


  1. 1.
    Turner R, Holman R, Cull C, Stratton I, Matthews D, Frighi V, Manley S, Neil A, Mcelroy K, Wright D (1998) Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 352(9131):837–853Google Scholar
  2. 2.
    Bell DSH (2003) Heart failure the frequent, forgotten, and often fatal complication of diabetes. Diabetes Care 26(8):2433–2441PubMedCrossRefGoogle Scholar
  3. 3.
    Galderisi M, Anderson KM, Wilson PW, Levy D (1991) Echocardiographic evidence for the existence of a distinct diabetic cardiomyopathy (the Framingham Heart Study). Am J Cardiol 68(1):85–89PubMedCrossRefGoogle Scholar
  4. 4.
    Kannel WB, Hjortland M, Castelli WP (1974) Role of diabetes in congestive heart failure: the Framingham study. Am J Cardiol 34(1):29–34PubMedCrossRefGoogle Scholar
  5. 5.
    Rutter MK, Parise H, Benjamin EJ, Levy D, Larson MG, Meigs JB, Nesto RW, Wilson PW, Vasan RS (2003) Impact of glucose intolerance and insulin resistance on cardiac structure and function: sex-related differences in the Framingham Heart Study. Circulation 107(3):448–454PubMedCrossRefGoogle Scholar
  6. 6.
    Fang ZY, Prins JB, Marwick TH (2004) Diabetic cardiomyopathy: evidence, mechanisms, and therapeutic implications. Endocr Rev 25(4):543–567. doi:10.1210/er.2003-0012 PubMedCrossRefGoogle Scholar
  7. 7.
    Aragno M, Mastrocola R, Alloatti G, Vercellinatto I, Bardini P, Geuna S, Catalano MG, Danni O, Boccuzzi G (2008) Oxidative stress triggers cardiac fibrosis in the heart of diabetic rats. Endocrinology 149(1):380–388. doi:10.1210/en.2007-0877 PubMedCrossRefGoogle Scholar
  8. 8.
    Ganguly PK, Pierce GN, Dhalla KS, Dhalla NS (1983) Defective sarcoplasmic reticular calcium transport in diabetic cardiomyopathy. Am J Physiol 244(6):E528–E535PubMedGoogle Scholar
  9. 9.
    Giacomelli F, Wiener J (1979) Primary myocardial disease in the diabetic mouse. An ultrastructural study. Lab Invest 40(4):460–473PubMedGoogle Scholar
  10. 10.
    Regan TJ, Wu CF, Yeh CK, Oldewurtel HA, Haider B (1981) Myocardial composition and function in diabetes. The effects of chronic insulin use. Circ Res 49(6):1268–1277PubMedCrossRefGoogle Scholar
  11. 11.
    Bell DS (2003) Diabetic cardiomyopathy. Diabetes Care 26(10):2949–2951PubMedCrossRefGoogle Scholar
  12. 12.
    Liu JE, Palmieri V, Roman MJ, Bella JN, Fabsitz R, Howard BV, Welty TK, Lee ET, Devereux RB (2001) The impact of diabetes on left ventricular filling pattern in normotensive and hypertensive adults: the Strong Heart Study. J Am Coll Cardiol 37(7):1943–1949PubMedCrossRefGoogle Scholar
  13. 13.
    Astorri E, Fiorina P, Contini GA, Albertini D, Magnati G, Astorri A, Lanfredini M (1997) Isolated and preclinical impairment of left ventricular filling in insulin-dependent and non-insulin-dependent diabetic patients. Clin Cardiol 20(6):536–540PubMedCrossRefGoogle Scholar
  14. 14.
    Miyata T, Sugiyama S, Saito A, Kurokawa K (2001) Reactive carbonyl compounds related uremic toxicity (“carbonyl stress”). Kidney Int 59:S25–S31CrossRefGoogle Scholar
  15. 15.
    Baynes JW, Thorpe SR (1999) Role of oxidative stress in diabetic complications: a new perspective on an old paradigm. Diabetes 48(1):1–9PubMedCrossRefGoogle Scholar
  16. 16.
    Suzuki D, Miyata T, Saotome N, Horie K, Inagi R, Yasuda Y, Uchida K, Izuhara Y, Yagame M, Sakai H, Kurokawa K (1999) Immunohistochemical evidence for an increased oxidative stress and carbonyl modification of proteins in diabetic glomerular lesions. J Am Soc Nephrol 10(4):822–832PubMedGoogle Scholar
  17. 17.
    Lo TW, Westwood ME, McLellan AC, Selwood T, Thornalley PJ (1994) 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. J Biol Chem 269(51):32299–32305PubMedGoogle Scholar
  18. 18.
    Frye EB, Degenhardt TP, Thorpe SR, Baynes JW (1998) Role of the Maillard reaction in aging of tissue proteins. Advanced glycation end product-dependent increase in imidazolium cross-links in human lens proteins. J Biol Chem 273(30):18714–18719PubMedCrossRefGoogle Scholar
  19. 19.
    Ahmed M, Thorpe S, Baynes J (1986) Identification of N epsilon-carboxymethyllysine as a degradation product of fructoselysine in glycated protein. J Biol Chem 261(11):4889–4894PubMedGoogle Scholar
  20. 20.
    Schmidt AM, Yan SD, Wautier JL, Stern D (1999) Activation of receptor for advanced glycation end products: a mechanism for chronic vascular dysfunction in diabetic vasculopathy and atherosclerosis. Circ Res 84(5):489–497PubMedCrossRefGoogle Scholar
  21. 21.
    Brownlee M, Vlassara H, Cerami A (1985) Nonenzymatic glycosylation products on collagen covalently trap low-density lipoprotein. Diabetes 34(9):938–941PubMedCrossRefGoogle Scholar
  22. 22.
    Knecht KJ, Feather MS, Baynes JW (1992) Detection of 3-deoxyfructose and 3-deoxyglucosone in human urine and plasma: evidence for intermediate stages of the Maillard reaction in vivo. Arch Biochem Biophys 294(1):130–137PubMedCrossRefGoogle Scholar
  23. 23.
    Monnier VM, Bautista O, Kenny D, Sell DR, Fogarty J, Dahms W, Cleary PA, Lachin J, Genuth S (1999) Skin collagen glycation, glycoxidation, and crosslinking are lower in subjects with long-term intensive versus conventional therapy of type 1 diabetes: relevance of glycated collagen products versus HbA1c as markers of diabetic complications. DCCT Skin Collagen Ancillary Study Group. Diabetes Control and Complications Trial. Diabetes 48(4):870–880PubMedCentralPubMedCrossRefGoogle Scholar
  24. 24.
    Meerwaldt R, Lutgers HL, Links TP, Graaff R, Baynes JW, Gans ROB, Smit AJ (2007) Skin autofluorescence is a strong predictor of cardiac mortality in diabetes. Diabetes Care 30(1):107–112PubMedCrossRefGoogle Scholar
  25. 25.
    Aronson D (2003) Cross-linking of glycated collagen in the pathogenesis of arterial and myocardial stiffening of aging and diabetes. J Hypertens 21(1):3–12. doi:10.1097/01.hjh.0000042892.24999.92 PubMedCrossRefGoogle Scholar
  26. 26.
    Schleicher ED, Wagner E, Nerlich AG (1997) Increased accumulation of the glycoxidation product N(epsilon)-(carboxymethyl)lysine in human tissues in diabetes and aging. J Clin Investig 99(3):457–468. doi:10.1172/JCI119180 PubMedCrossRefGoogle Scholar
  27. 27.
    Schalkwijk CG, Baidoshvili A, Stehouwer CDA, van Hinsbergh VWM, Niessen HWM (2004) Increased accumulation of the glycoxidation product Nε-(carboxymethyl)lysine in hearts of diabetic patients: generation and characterisation of a monoclonal anti-CML antibody. Biochimica Biophysica Acta Mol Cell Biol Lipids 1636(2):82–89CrossRefGoogle Scholar
  28. 28.
    Hartog JW, de Vries AP, Bakker SJ, Graaff R, van Son WJ, van der Heide JJ, Gans RO, Wolffenbuttel BH, de Jong PE, Smit AJ (2006) Risk factors for chronic transplant dysfunction and cardiovascular disease are related to accumulation of advanced glycation end-products in renal transplant recipients. Nephrology, dialysis, transplantation: official publication of the European Dialysis and Transplant Association—European Renal Association 21 (8):2263–2269. doi:10.1093/ndt/gfl132
  29. 29.
    Hartog JWL, Vries APJ, Lutgers HL, Meerwaldt R, Huisman RM, Son WJ, Jong PE, Smit AJ (2005) Accumulation of advanced glycation end products, measured as skin autofluorescence, in renal disease. Ann N Y Acad Sci 1043(1):299–307Google Scholar
  30. 30.
    Uribarri J, Peppa M, Cai W, Goldberg T, Lu M, He C, Vlassara H (2003) Restriction of dietary glycotoxins reduces excessive advanced glycation end products in renal failure patients. J Am Soc Nephrol 14(3):728–731PubMedCrossRefGoogle Scholar
  31. 31.
    Cerami C, Founds H, Nicholl I, Mitsuhashi T, Giordano D, Vanpatten S, Lee A, Al-Abed Y, Vlassara H, Bucala R (1997) Tobacco smoke is a source of toxic reactive glycation products. Proc Natl Acad Sci 94(25):13915–13920PubMedCrossRefGoogle Scholar
  32. 32.
    Goh SY, Cooper ME (2008) Clinical review: the role of advanced glycation end products in progression and complications of diabetes. J Clin Endocrinol Metab 93(4):1143–1152. doi:10.1210/jc.2007-1817 PubMedCrossRefGoogle Scholar
  33. 33.
    Avendano GF, Agarwal RK, Bashey RI, Lyons MM, Soni BJ, Jyothirmayi GN, Regan TJ (1999) Effects of glucose intolerance on myocardial function and collagen-linked glycation. Diabetes 48(7):1443–1447PubMedCrossRefGoogle Scholar
  34. 34.
    Kumari K, Sahib MK (1993) Susceptibility of different rat tissues to non-enzymatic protein glycosylation in experimental diabetes. Indian J Exp Biol 31(2):194–195PubMedGoogle Scholar
  35. 35.
    Berg TJ, Dahl-Jorgensen K, Torjesen PA, Hanssen KF (1997) Increased serum levels of advanced glycation end products (AGEs) in children and adolescents with IDDM. Diabetes Care 20(6):1006–1008PubMedCrossRefGoogle Scholar
  36. 36.
    Nozynski J, Zakliczynski M, Konecka-Mrowka D, Nikiel B, Mlynarczyk-Liszka J, Zembala-Nozynska E, Lange D, Maruszewski M, Zembala M (2009) Advanced glycation end products in the development of ischemic and dilated cardiomyopathy in patients with diabetes mellitus type 2. Transpl Proc 41(1):99–104. doi:10.1016/j.transproceed.2008.09.065 CrossRefGoogle Scholar
  37. 37.
    Nożyński J, Zakliczyński M, Konecka-Mrowka D, Zielinska T, Zakliczynska H, Nikiel B, Mlynarczyk-Liszka J, Mrowka A, Zembala-Nozynska E, Pijet M (2012) Advanced glycation end product accumulation in the cardiomyocytes of heart failure patients with and without diabetes. Ann Trans Q Polish Trans Soc 17(2):53–61Google Scholar
  38. 38.
    Vlassara H, Palace MR (2002) Diabetes and advanced glycation endproducts. J Intern Med 251(2):87–101PubMedCrossRefGoogle Scholar
  39. 39.
    Cooper ME (2004) Importance of advanced glycation end products in diabetes-associated cardiovascular and renal disease. Am J Hypertens 17(12 Pt 2):31S–38S. doi:10.1016/j.amjhyper.2004.08.021 PubMedCrossRefGoogle Scholar
  40. 40.
    Huebschmann AG, Regensteiner JG, Vlassara H, Reusch JE (2006) Diabetes and advanced glycoxidation end products. Diabetes Care 29(6):1420–1432. doi:10.2337/dc05-2096 PubMedCrossRefGoogle Scholar
  41. 41.
    Kiuchi K, Nejima J, Takano T, Ohta M, Hashimoto H (2001) Increased serum concentrations of advanced glycation end products: a marker of coronary artery disease activity in type 2 diabetic patients. Heart 85(1):87–91PubMedCrossRefGoogle Scholar
  42. 42.
    Berg TJ, Snorgaard O, Faber J, Torjesen PA, Hildebrandt P, Mehlsen J, Hanssen KF (1999) Serum levels of advanced glycation end products are associated with left ventricular diastolic function in patients with type 1 diabetes. Diabetes Care 22(7):1186–1190PubMedCrossRefGoogle Scholar
  43. 43.
    Baynes JW, Thorpe SR (2000) Glycoxidation and lipoxidation in atherogenesis. Free Radical Biol Med 28(12):1708–1716CrossRefGoogle Scholar
  44. 44.
    Hricik DE, Wu YC, Schulak A, Friedlander MA (1996) Disparate changes in plasma and tissue pentosidine levels after kidney and kidney-pancreas transplantation. Clin Transpl 10(6 Pt 1):568–573Google Scholar
  45. 45.
    Dorrian CA, Cathcart S, Clausen J, Shapiro D, Dominiczak MH (1998) Factors in human serum interfere with the measurement of advanced glycation endproducts. Cell Mol Biol 44(7):1069–1079PubMedGoogle Scholar
  46. 46.
    Garvey WT, Hardin D, Juhaszova M, Dominguez JH (1993) Effects of diabetes on myocardial glucose transport system in rats: implications for diabetic cardiomyopathy. Am J Physiol 264(3 Pt 2):H837–H844PubMedGoogle Scholar
  47. 47.
    Rodrigues B, Cam MC, Kong J, Goyal RK, McNeill JH (1997) Strain differences in susceptibility to streptozotocin-induced diabetes: effects on hypertriglyceridemia and cardiomyopathy. Cardiovasc Res 34(1):199–205PubMedCrossRefGoogle Scholar
  48. 48.
    Hall JL, Henderson J, Hernandez LA, Kellerman LA, Stanley WC (1996) Hyperglycemia results in an increase in myocardial interstitial glucose and glucose uptake during ischemia. Metabolism 45(5):542–549PubMedCrossRefGoogle Scholar
  49. 49.
    Bell GI, Kayano T, Buse JB, Burant CF, Takeda J, Lin D, Fukumoto H, Seino S (1990) Molecular biology of mammalian glucose transporters. Diabetes Care 13(3):198–208PubMedCrossRefGoogle Scholar
  50. 50.
    James DE, Strube M, Mueckler M (1989) Molecular cloning and characterization of an insulin-regulatable glucose transporter. Nature 338(6210):83–87. doi:10.1038/338083a0 PubMedCrossRefGoogle Scholar
  51. 51.
    Doria-Medina CL, Lund DD, Pasley A, Sandra A, Sivitz WI (1993) Immunolocalization of GLUT-1 glucose transporter in rat skeletal muscle and in normal and hypoxic cardiac tissue. Am J Physiol 265(3 Pt 1):E454–E464PubMedGoogle Scholar
  52. 52.
    Kraegen EW, Sowden JA, Halstead MB, Clark PW, Rodnick KJ, Chisholm DJ, James DE (1993) Glucose transporters and in vivo glucose uptake in skeletal and cardiac muscle: fasting, insulin stimulation and immunoisolation studies of GLUT1 and GLUT4. Biochem J 295(Pt 1):287–293Google Scholar
  53. 53.
    Sun D, Nguyen N, DeGrado TR, Schwaiger M, Brosius FC 3rd (1994) Ischemia induces translocation of the insulin-responsive glucose transporter GLUT4 to the plasma membrane of cardiac myocytes. Circulation 89(2):793–798PubMedCrossRefGoogle Scholar
  54. 54.
    Slot JW, Geuze HJ, Gigengack S, James DE, Lienhard GE (1991) Translocation of the glucose transporter GLUT4 in cardiac myocytes of the rat. Proc Natl Acad Sci USA 88(17):7815–7819PubMedCrossRefGoogle Scholar
  55. 55.
    Flier JS, Mueckler MM, Usher P, Lodish HF (1987) Elevated levels of glucose transport and transporter messenger RNA are induced by ras or src oncogenes. Science 235(4795):1492–1495PubMedCrossRefGoogle Scholar
  56. 56.
    Razeghi P, Young ME, Ying J, Depre C, Uray IP, Kolesar J, Shipley GL, Moravec CS, Davies PJA, Frazier O (2002) Downregulation of metabolic gene expression in failing human heart before and after mechanical unloading. Cardiology 97(4):203–209PubMedCrossRefGoogle Scholar
  57. 57.
    Santalucia T, Boheler KR, Brand NJ, Sahye U, Fandos C, Vinals F, Ferre J, Testar X, Palacin M, Zorzano A (1999) Factors involved in GLUT-1 glucose transporter gene transcription in cardiac muscle. J Biol Chem 274(25):17626–17634PubMedCrossRefGoogle Scholar
  58. 58.
    Taegtmeyer H (1994) Energy metabolism of the heart: from basic concepts to clinical applications. Curr Probl Cardiol 19(2):59–113PubMedCrossRefGoogle Scholar
  59. 59.
    Russell RR III, Mrus JM, Mommessin JI, Taegtmeyer H (1992) Compartmentation of hexokinase in rat heart. A critical factor for tracer kinetic analysis of myocardial glucose metabolism. J Clin Investig 90(5):1972–1977. doi:10.1172/JCI116076 Google Scholar
  60. 60.
    Ma H, Li SY, Xu P, Babcock SA, Dolence EK, Brownlee M, Li J, Ren J (2009) Advanced glycation endproduct (AGE) accumulation and AGE receptor (RAGE) up-regulation contribute to the onset of diabetic cardiomyopathy. J Cell Mol Med 13(8B):1751–1764. doi:10.1111/j.1582-4934.2008.00547.x Google Scholar
  61. 61.
    Hofmann MA, Drury S, Fu C, Qu W, Taguchi A, Lu Y, Avila C, Kambham N, Bierhaus A, Nawroth P, Neurath MF, Slattery T, Beach D, McClary J, Nagashima M, Morser J, Stern D, Schmidt AM (1999) RAGE mediates a novel proinflammatory axis: a central cell surface receptor for S100/calgranulin polypeptides. Cell 97(7):889–901PubMedCrossRefGoogle Scholar
  62. 62.
    Giardino I, Edelstein D, Brownlee M (1994) Nonenzymatic glycosylation in vitro and in bovine endothelial cells alters basic fibroblast growth factor activity. A model for intracellular glycosylation in diabetes. J Clin Investig 94(1):110–117. doi:10.1172/JCI117296 PubMedCrossRefGoogle Scholar
  63. 63.
    Szwergold BS, Kappler F, Brown TR (1990) Identification of fructose 3-phosphate in the lens of diabetic rats. Science 247(4941):451–454PubMedCrossRefGoogle Scholar
  64. 64.
    Baynes JW (2002) The Maillard hypothesis on aging: time to focus on DNA. Ann N Y Acad Sci 959(1):360–367PubMedCrossRefGoogle Scholar
  65. 65.
    Thornalley P, Westwood M, Lo T, McLellan A (1995) Formation of methylglyoxal-modified proteins in vitro and in vivo and their involvement in AGE-related processes. Contrib Nephrol 112:24–31PubMedGoogle Scholar
  66. 66.
    Thornalley PJ, Langborg A, Minhas HS (1999) Formation of glyoxal, methylglyoxal and 3-deoxyglucosone in the glycation of proteins by glucose. Biochem J 344(Pt 1):109–116Google Scholar
  67. 67.
    Shinohara M, Thornalley PJ, Giardino I, Beisswenger P, Thorpe SR, Onorato J, Brownlee M (1998) Overexpression of glyoxalase-I in bovine endothelial cells inhibits intracellular advanced glycation endproduct formation and prevents hyperglycemia-induced increases in macromolecular endocytosis. J Clin Investig 101(5):1142–1147. doi:10.1172/JCI119885 PubMedCrossRefGoogle Scholar
  68. 68.
    Thornalley PJ (2003) Glyoxalase I–structure, function and a critical role in the enzymatic defence against glycation. Biochem Soc Trans 31(Pt 6):1343–1348. doi:10.1042/ PubMedCrossRefGoogle Scholar
  69. 69.
    Ko J, Kim I, Yoo S, Min B, Kim K, Park C (2005) Conversion of methylglyoxal to acetol by Escherichia coli aldo-keto reductases. J Bacteriol 187(16):5782–5789. doi:10.1128/JB.187.16.5782-5789.2005 PubMedCentralPubMedCrossRefGoogle Scholar
  70. 70.
    Misra K, Banerjee AB, Ray S, Ray M (1996) Reduction of methylglyoxal in Escherichia coli K 12 by an aldehyde reductase and alcohol dehydrogenase. Mol Cell Biochem 156(2):117–124PubMedCrossRefGoogle Scholar
  71. 71.
    Baba SP, Barski OA, Ahmed Y, O’Toole TE, Conklin DJ, Bhatnagar A, Srivastava S (2009) Reductive metabolism of AGE precursors: a metabolic route for preventing AGE accumulation in cardiovascular tissue. Diabetes 58(11):2486–2497. doi:10.2337/db09-0375 PubMedCrossRefGoogle Scholar
  72. 72.
    Penpargkul S, Fein F, Sonnenblick EH, Scheuer J (1981) Depressed cardiac sarcoplasmic reticular function from diabetic rats. J Mol Cell Cardiol 13(3):303–309PubMedCrossRefGoogle Scholar
  73. 73.
    Bouchard RA, Bose D (1991) Influence of experimental diabetes on sarcoplasmic reticulum function in rat ventricular muscle. Am J Physiol 260(2 Pt 2):H341–H354PubMedGoogle Scholar
  74. 74.
    Lagadic-Gossmann D, Buckler KJ, Le Prigent K, Feuvray D (1996) Altered Ca2+ handling in ventricular myocytes isolated from diabetic rats. Am J Physiol 270(5 Pt 2):H1529–H1537PubMedGoogle Scholar
  75. 75.
    Hansford RG (1994) Physiological role of mitochondrial Ca 2+ transport. J Bioenerg Biomembr 26(5):495–508PubMedCrossRefGoogle Scholar
  76. 76.
    Davidoff AJ, Mason MM, Davidson MB, Carmody MW, Hintz KK, Wold LE, Podolin DA, Ren J (2004) Sucrose-induced cardiomyocyte dysfunction is both preventable and reversible with clinically relevant treatments. Am J Physiol Endocrinol Metab 286(5):E718–E724PubMedCrossRefGoogle Scholar
  77. 77.
    Trost SU, Belke DD, Bluhm WF, Meyer M, Swanson E, Dillmann WH (2002) Overexpression of the sarcoplasmic reticulum Ca2+-ATPase improves myocardial contractility in diabetic cardiomyopathy. Diabetes 51(4):1166–1171PubMedCrossRefGoogle Scholar
  78. 78.
    Belke DD, Betuing S, Tuttle MJ, Graveleau C, Young ME, Pham M, Zhang D, Cooksey RC, McClain DA, Litwin SE, Taegtmeyer H, Severson D, Kahn CR, Abel ED (2002) Insulin signaling coordinately regulates cardiac size, metabolism, and contractile protein isoform expression. J Clin Investig 109(5):629–639. doi:10.1172/JCI13946 PubMedGoogle Scholar
  79. 79.
    Aasum E, Hafstad AD, Severson DL, Larsen TS (2003) Age-dependent changes in metabolism, contractile function, and ischemic sensitivity in hearts from db/db mice. Diabetes 52(2):434–441PubMedCrossRefGoogle Scholar
  80. 80.
    Bidasee KR, Zhang Y, Shao CH, Wang M, Patel KP, Dincer UD, Besch HR Jr (2004) Diabetes increases formation of advanced glycation end products on Sarco(endo)plasmic reticulum Ca2+-ATPase. Diabetes 53(2):463–473PubMedCrossRefGoogle Scholar
  81. 81.
    Bidasee KR, Nallani K, Yu Y, Cocklin RR, Zhang Y, Wang M, Dincer UD, Besch HR Jr (2003) Chronic diabetes increases advanced glycation end products on cardiac ryanodine receptors/calcium-release channels. Diabetes 52(7):1825–1836PubMedCrossRefGoogle Scholar
  82. 82.
    Bers DM (2002) Cardiac excitation-contraction coupling. Nature 415(6868):198–205. doi:10.1038/415198a PubMedCrossRefGoogle Scholar
  83. 83.
    Guner S, Arioglu E, Tay A, Tasdelen A, Aslamaci S, Bidasee KR, Dincer UD (2002) Diabetes alter mRNA levels of calcium-release channels in human atrial appendage. J Mol Cell Cardiol 34(6):A84CrossRefGoogle Scholar
  84. 84.
    Razeghi P, Young ME, Cockrill TC, Frazier OH, Taegtmeyer H (2002) Downregulation of myocardial myocyte enhancer factor 2C and myocyte enhancer factor 2C-regulated gene expression in diabetic patients with nonischemic heart failure. Circulation 106(4):407–411PubMedCrossRefGoogle Scholar
  85. 85.
    Yu Z, Tibbits GF, McNeill JH (1994) Cellular functions of diabetic cardiomyocytes: contractility, rapid-cooling contracture, and ryanodine binding. Am J Physiol 266(5 Pt 2):H2082–H2089PubMedGoogle Scholar
  86. 86.
    Teshima Y, Takahashi N, Saikawa T, Hara M, Yasunaga S, Hidaka S, Sakata T (2000) Diminished expression of sarcoplasmic reticulum Ca <sup> 2+ </sup>-ATPase and Ryanodine Sensitive Ca <sup> 2+ </sup> Channel mRNA in Streptozotocin-induced Diabetic Rat Heart. J Mol Cell Cardiol 32(4):655–664PubMedCrossRefGoogle Scholar
  87. 87.
    Netticadan T, Temsah RM, Kent A, Elimban V, Dhalla NS (2001) Depressed levels of Ca2+-cycling proteins may underlie sarcoplasmic reticulum dysfunction in the diabetic heart. Diabetes 50(9):2133–2138PubMedCrossRefGoogle Scholar
  88. 88.
    Zhong Y, Ahmed S, Grupp IL, Matlib MA (2001) Altered SR protein expression associated with contractile dysfunction in diabetic rat hearts. Am J Physiol Heart Circ Physiol 281(3):H1137–H1147PubMedGoogle Scholar
  89. 89.
    Bidasee KR, Dincer UD, Besch HR Jr (2001) Ryanodine receptor dysfunction in hearts of streptozotocin-induced diabetic rats. Mol Pharmacol 60(6):1356–1364PubMedGoogle Scholar
  90. 90.
    Bidasee KR, Nallani K, Henry B, Dincer UD, Besch HR Jr (2003) Chronic diabetes alters function and expression of ryanodine receptor calcium-release channels in rat hearts. Mol Cell Biochem 249(1–2):113–123PubMedCrossRefGoogle Scholar
  91. 91.
    Ren J, Gintant GA, Miller RE, Davidoff AJ (1997) High extracellular glucose impairs cardiac EC coupling in a glycosylation-dependent manner. Am J Physiol Heart Circ Physiol 273(6):H2876–H2883Google Scholar
  92. 92.
    Parker GJ, Lund KC, Taylor RP, McClain DA (2003) Insulin resistance of glycogen synthase mediated byo-linked N-acetylglucosamine. J Biol Chem 278(12):10022–10027PubMedCrossRefGoogle Scholar
  93. 93.
    Marshall S, Garvey W, Traxinger R (1991) New insights into the metabolic regulation of insulin action and insulin resistance: role of glucose and amino acids. FASEB J 5(15):3031–3036PubMedGoogle Scholar
  94. 94.
    Vosseller K, Wells L, Lane MD, Hart GW (2002) Elevated nucleocytoplasmic glycosylation by O-GlcNAc results in insulin resistance associated with defects in Akt activation in 3T3-L1 adipocytes. Proc Natl Acad Sci USA 99(8):5313–5318. doi:10.1073/pnas.072072399 PubMedCrossRefGoogle Scholar
  95. 95.
    Clark RJ, McDonough PM, Swanson E, Trost SU, Suzuki M, Fukuda M, Dillmann WH (2003) Diabetes and the accompanying hyperglycemia impairs cardiomyocyte calcium cycling through increased nuclear O-GlcNAcylation. J Biol Chem 278(45):44230–44237PubMedCrossRefGoogle Scholar
  96. 96.
    Baker DL, Dave V, Reed T, Periasamy M (1996) Multiple Sp1 binding sites in the Cardiac/Slow Twitch Muscle Sarcoplamsic Reticulum Ca-ATPase gene promoter are required for expression in Sol8 muscle cells. J Biol Chem 271(10):5921–5928PubMedCrossRefGoogle Scholar
  97. 97.
    Yang X, Su K, Roos MD, Chang Q, Paterson AJ, Kudlow JE (2001) O-linkage of N-acetylglucosamine to Sp1 activation domain inhibits its transcriptional capability. Proc Natl Acad Sci USA 98(12):6611–6616. doi:10.1073/pnas.111099998 PubMedCrossRefGoogle Scholar
  98. 98.
    Smit AJ, Lutgers HL (2004) The clinical relevance of advanced glycation endproducts (AGE) and recent developments in pharmaceutics to reduce AGE accumulation. Curr Med Chem 11(20):2767–2784PubMedCrossRefGoogle Scholar
  99. 99.
    Brownlee M (1995) Advanced protein glycosylation in diabetes and aging. Annu Rev Med 46(1):223–234. doi:10.1146/annurev.med.46.1.223 PubMedCrossRefGoogle Scholar
  100. 100.
    Tanaka S, Avigad G, Brodsky B, Eikenberry EF (1988) Glycation induces expansion of the molecular packing of collagen. J Mol Biol 203(2):495–505PubMedCrossRefGoogle Scholar
  101. 101.
    Haitoglou C, Tsilibary E, Brownlee M, Charonis A (1992) Altered cellular interactions between endothelial cells and nonenzymatically glucosylated laminin/type IV collagen. J Biol Chem 267(18):12404–12407PubMedGoogle Scholar
  102. 102.
    Kass DA, Shapiro EP, Kawaguchi M, Capriotti AR, Scuteri A, deGroof RC, Lakatta EG (2001) Improved arterial compliance by a novel advanced glycation end-product crosslink breaker. Circulation 104(13):1464–1470PubMedCrossRefGoogle Scholar
  103. 103.
    Paul RG, Bailey AJ (1999) The effect of advanced glycation end-product formation upon cell-matrix interactions. Int J Biochem Cell Biol 31(6):653–660PubMedCrossRefGoogle Scholar
  104. 104.
    Bucala R, Makita Z, Vega G, Grundy S, Koschinsky T, Cerami A, Vlassara H (1994) Modification of low density lipoprotein by advanced glycation end products contributes to the dyslipidemia of diabetes and renal insufficiency. Proc Natl Acad Sci USA 91(20):9441–9445PubMedCrossRefGoogle Scholar
  105. 105.
    Posch K, Simecek S, Wascher TC, Jurgens G, Baumgartner-Parzer S, Kostner GM, Graier WF (1999) Glycated low-density lipoprotein attenuates shear stress-induced nitric oxide synthesis by inhibition of shear stress-activated l-arginine uptake in endothelial cells. Diabetes 48(6):1331–1337PubMedCrossRefGoogle Scholar
  106. 106.
    Gempel KE, Gerbitz KD, Olgemoller B, Schleicher ED (1993) In-vitro carboxymethylation of low density lipoprotein alters its metabolism via the high-affinity receptor. Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme 25(5):250–252. doi:10.1055/s-2007-1002089
  107. 107.
    Brett J, Schmidt AM, Yan SD, Zou YS, Weidman E, Pinsky D, Nowygrod R, Neeper M, Przysiecki C, Shaw A et al (1993) Survey of the distribution of a newly characterized receptor for advanced glycation end products in tissues. Am J Pathol 143(6):1699–1712PubMedGoogle Scholar
  108. 108.
    Striker LJ, Striker GE (1996) Administration of AGEs in vivo induces extracellular matrix gene expression. Nephrology, dialysis, transplantation: official publication of the European Dialysis and Transplant Association—European Renal Association 11(suppl 5):62–65Google Scholar
  109. 109.
    Throckmorton DC, Brogden AP, Min B, Rasmussen H, Kashgarian M (1995) PDGF and TGF-bold beta mediate collagen production by mesangial cells exposed to advanced glycosylation end products. Kidney Int 48:111–117PubMedCrossRefGoogle Scholar
  110. 110.
    Bucala R, Tracey KJ, Cerami A (1991) Advanced glycosylation products quench nitric oxide and mediate defective endothelium-dependent vasodilatation in experimental diabetes. J Clin Investig 87(2):432–438. doi:10.1172/JCI115014 PubMedCrossRefGoogle Scholar
  111. 111.
    Schmidt AM, Vianna M, Gerlach M, Brett J, Ryan J, Kao J, Esposito C, Hegarty H, Hurley W, Clauss M (1992) Isolation and characterization of two binding proteins for advanced glycosylation end products from bovine lung which are present on the endothelial cell surface. J Biol Chem 267(21):14987–14997PubMedGoogle Scholar
  112. 112.
    Neeper M, Schmidt AM, Brett J, Yan SD, Wang F, Pan YC, Elliston K, Stern D, Shaw A (1992) Cloning and expression of a cell surface receptor for advanced glycosylation end products of proteins. J Biol Chem 267(21):14998–15004PubMedGoogle Scholar
  113. 113.
    Bucciarelli LG, Ananthakrishnan R, Hwang YC, Kaneko M, Song F, Sell DR, Strauch C, Monnier VM, Yan SF, Schmidt AM, Ramasamy R (2008) RAGE and modulation of ischemic injury in the diabetic myocardium. Diabetes 57(7):1941–1951. doi:10.2337/db07-0326 PubMedCrossRefGoogle Scholar
  114. 114.
    Sugaya K, Fukagawa T, Matsumoto K, Mita K, Takahashi E, Ando A, Inoko H, Ikemura T (1994) Three genes in the human MHC class III region near the junction with the class II: gene for receptor of advanced glycosylation end products, PBX2 homeobox gene and a notch homolog, human counterpart of mouse mammary tumor gene int-3. Genomics 23(2):408–419PubMedCrossRefGoogle Scholar
  115. 115.
    Li J, Schmidt AM (1997) Characterization and functional analysis of the promoter of RAGE, the receptor for advanced glycation end products. J Biol Chem 272(26):16498–16506PubMedCrossRefGoogle Scholar
  116. 116.
    Yan SF, Ramasamy R, Naka Y, Schmidt AM (2003) Glycation, inflammation, and RAGE: a scaffold for the macrovascular complications of diabetes and beyond. Circ Res 93(12):1159–1169. doi:10.1161/01.RES.0000103862.26506.3D PubMedCrossRefGoogle Scholar
  117. 117.
    Kislinger T, Fu C, Huber B, Qu W, Taguchi A, Du Yan S, Hofmann M, Yan SF, Pischetsrieder M, Stern D (1999) N ε-(carboxymethyl) lysine adducts of proteins are ligands for receptor for advanced glycation end products that activate cell signaling pathways and modulate gene expression. J Biol Chem 274(44):31740–31749PubMedCrossRefGoogle Scholar
  118. 118.
    Schmidt AM, Yan SD, Yan SF, Stern DM (2001) The multiligand receptor RAGE as a progression factor amplifying immune and inflammatory responses. J Clin Investig 108(7):949–956PubMedGoogle Scholar
  119. 119.
    Makita Z, Vlassara H, Rayfield E, Cartwright K, Friedman E, Rodby R, Cerami A, Bucala R (1992) Hemoglobin-AGE: a circulating marker of advanced glycosylation. Science 258(5082):651–653PubMedCrossRefGoogle Scholar
  120. 120.
    Dyer DG, Dunn JA, Thorpe SR, Bailie KE, Lyons TJ, McCance DR, Baynes JW (1993) Accumulation of Maillard reaction products in skin collagen in diabetes and aging. J Clin Investig 91(6):2463–2469. doi:10.1172/JCI116481 PubMedCrossRefGoogle Scholar
  121. 121.
    Goldin A, Beckman JA, Schmidt AM, Creager MA (2006) Advanced glycation end products: sparking the development of diabetic vascular injury. Circulation 114(6):597–605. doi:10.1161/CIRCULATIONAHA.106.621854 PubMedCrossRefGoogle Scholar
  122. 122.
    Stern DM, Yan SD, Yan SF, Schmidt AM (2002) Receptor for advanced glycation endproducts (RAGE) and the complications of diabetes. Ageing Res Rev 1(1):1–15PubMedCrossRefGoogle Scholar
  123. 123.
    Bierhaus A, Humpert PM, Morcos M, Wendt T, Chavakis T, Arnold B, Stern DM, Nawroth PP (2005) Understanding RAGE, the receptor for advanced glycation end products. J Mol Med (Berl) 83(11):876–886. doi:10.1007/s00109-005-0688-7 CrossRefGoogle Scholar
  124. 124.
    Park L, Raman KG, Lee KJ, Lu Y, Ferran LJ Jr, Chow WS, Stern D, Schmidt AM (1998) Suppression of accelerated diabetic atherosclerosis by the soluble receptor for advanced glycation endproducts. Nat Med 4(9):1025–1031. doi:10.1038/2012 PubMedCrossRefGoogle Scholar
  125. 125.
    Sakaguchi T, Yan SF, Yan SD, Belov D, Rong LL, Sousa M, Andrassy M, Marso SP, Duda S, Arnold B, Liliensiek B, Nawroth PP, Stern DM, Schmidt AM, Naka Y (2003) Central role of RAGE-dependent neointimal expansion in arterial restenosis. J Clin Investig 111(7):959–972. doi:10.1172/JCI17115 PubMedGoogle Scholar
  126. 126.
    Goova MT, Li J, Kislinger T, Qu W, Lu Y, Bucciarelli LG, Nowygrod S, Wolf BM, Caliste X, Yan SF, Stern DM, Schmidt AM (2001) Blockade of receptor for advanced glycation end-products restores effective wound healing in diabetic mice. Am J Pathol 159(2):513–525. doi:10.1016/S0002-9440(10)61723-3 PubMedCrossRefGoogle Scholar
  127. 127.
    Wendt TM, Tanji N, Guo J, Kislinger TR, Qu W, Lu Y, Bucciarelli LG, Rong LL, Moser B, Markowitz GS, Stein G, Bierhaus A, Liliensiek B, Arnold B, Nawroth PP, Stern DM, D’Agati VD, Schmidt AM (2003) RAGE drives the development of glomerulosclerosis and implicates podocyte activation in the pathogenesis of diabetic nephropathy. Am J Pathol 162(4):1123–1137. doi:10.1016/S0002-9440(10)63909-0 PubMedCrossRefGoogle Scholar
  128. 128.
    Nielsen JM, Kristiansen SB, Norregaard R, Andersen CL, Denner L, Nielsen TT, Flyvbjerg A, Botker HE (2009) Blockage of receptor for advanced glycation end products prevents development of cardiac dysfunction in db/db type 2 diabetic mice. Eur J Heart Fail 11(7):638–647. doi:10.1093/eurjhf/hfp070 PubMedCrossRefGoogle Scholar
  129. 129.
    Bu DX, Rai V, Shen X, Rosario R, Lu Y, D’Agati V, Yan SF, Friedman RA, Nuglozeh E, Schmidt AM (2010) Activation of the ROCK1 branch of the transforming growth factor-beta pathway contributes to RAGE-dependent acceleration of atherosclerosis in diabetic ApoE-null mice. Circ Res 106(6):1040–1051. doi:10.1161/CIRCRESAHA.109.201103 PubMedCentralPubMedCrossRefGoogle Scholar
  130. 130.
    Stitt AW, Bucala R, Vlassara H (2006) Atherogenesis and advanced glycation: promotion, progression, and prevention. Ann N Y Acad Sci 811(1):115–129Google Scholar
  131. 131.
    Bucciarelli L, Wendt T, Rong L, Lalla E, Hofmann M, Goova M, Taguchi A, Yan S, Yan S, Stern D (2002) RAGE is a multiligand receptor of the immunoglobulin superfamily: implications for homeostasis and chronic disease. Cell Mol Life Sci 59(7):1117–1128PubMedCrossRefGoogle Scholar
  132. 132.
    Kim W, Hudson BI, Moser B, Guo J, Rong LL, Lu Y, Qu W, Lalla E, Lerner S (1043) Chen Y (2006) Receptor for advanced glycation end products and its ligands: a journey from the complications of diabetes to its pathogenesis. Ann N Y Acad Sci 1:553–561Google Scholar
  133. 133.
    Thornalley PJ (1990) The glyoxalase system: new developments towards functional characterization of a metabolic pathway fundamental to biological life. Biochem J 269(1):1–11PubMedGoogle Scholar
  134. 134.
    Thornalley PJ (1998) Glutathione-dependent detoxification of alpha-oxoaldehydes by the glyoxalase system: involvement in disease mechanisms and antiproliferative activity of glyoxalase I inhibitors. Chem Biol Interact 111–112:137–151PubMedCrossRefGoogle Scholar
  135. 135.
    Szwergold BS, Howell S, Beisswenger PJ (2001) Human fructosamine-3-kinase: purification, sequencing, substrate specificity, and evidence of activity in vivo. Diabetes 50(9):2139–2147PubMedCrossRefGoogle Scholar
  136. 136.
    Boel E, Selmer J, Flodgaard HJ, Jensen T (1995) Diabetic late complications: will aldose reductase inhibitors or inhibitors of advanced glycosylation endproduct formation hold promise? J Diabetes Complicat 9(2):104–129PubMedCrossRefGoogle Scholar
  137. 137.
    Suzuki K, Koh YH, Mizuno H, Hamaoka R, Taniguchi N (1998) Overexpression of aldehyde reductase protects PC12 cells from the cytotoxicity of methylglyoxal or 3-deoxyglucosone. J Biochem 123(2):353–357PubMedCrossRefGoogle Scholar
  138. 138.
    Vander Jagt DL, Hassebrook RK, Hunsaker LA, Brown WM, Royer RE (2001) Metabolism of the 2-oxoaldehyde methylglyoxal by aldose reductase and by glyoxalase-I: roles for glutathione in both enzymes and implications for diabetic complications. Chem Biol Interact 130(1–3):549PubMedCrossRefGoogle Scholar
  139. 139.
    Vasan S, Zhang X, Zhang X, Kapurniotu A, Bernhagen J, Teichberg S, Basgen J, Wagle D, Shih D, Terlecky I, Bucala R, Cerami A, Egan J, Ulrich P (1996) An agent cleaving glucose-derived protein crosslinks in vitro and in vivo. Nature 382(6588):275–278. doi:10.1038/382275a0 PubMedCrossRefGoogle Scholar
  140. 140.
    Wolffenbuttel BH, Boulanger CM, Crijns FR, Huijberts MS, Poitevin P, Swennen GN, Vasan S, Egan JJ, Ulrich P, Cerami A, Levy BI (1998) Breakers of advanced glycation end products restore large artery properties in experimental diabetes. Proc Natl Acad Sci USA 95(8):4630–4634PubMedCrossRefGoogle Scholar
  141. 141.
    Huijberts MS, Wolffenbuttel BH, Boudier HA, Crijns FR, Kruseman AC, Poitevin P, Levy BI (1993) Aminoguanidine treatment increases elasticity and decreases fluid filtration of large arteries from diabetic rats. J Clin Investig 92(3):1407–1411. doi:10.1172/JCI116716 PubMedCrossRefGoogle Scholar
  142. 142.
    Asif M, Egan J, Vasan S, Jyothirmayi GN, Masurekar MR, Lopez S, Williams C, Torres RL, Wagle D, Ulrich P (2000) An advanced glycation endproduct cross-link breaker can reverse age-related increases in myocardial stiffness. Proc Natl Acad Sci 97(6):2809–2813PubMedCrossRefGoogle Scholar
  143. 143.
    Vaitkevicius PV, Lane M, Spurgeon H, Ingram DK, Roth GS, Egan JJ, Vasan S, Wagle DR, Ulrich P, Brines M (2001) A cross-link breaker has sustained effects on arterial and ventricular properties in older rhesus monkeys. Proc Natl Acad Sci 98(3):1171–1175PubMedCrossRefGoogle Scholar
  144. 144.
    Liu J, Masurekar MR, Vatner DE, Jyothirmayi GN, Regan TJ, Vatner SF, Meggs LG, Malhotra A (2003) Glycation end-product cross-link breaker reduces collagen and improves cardiac function in aging diabetic heart. Am J Physiol Heart Circ Physiol 285(6):H2587–H2591. doi:10.1152/ajpheart.00516.2003 PubMedGoogle Scholar
  145. 145.
    Susic D, Varagic J, Ahn J, Frohlich ED (2004) Cardiovascular and renal effects of a collagen cross-link breaker (ALT 711) in adult and aged spontaneously hypertensive rats. Am J Hypertens 17(4):328–333. doi:10.1016/j.amjhyper.2003.12.015 PubMedCrossRefGoogle Scholar
  146. 146.
    Candido R, Forbes JM, Thomas MC, Thallas V, Dean RG, Burns WC, Tikellis C, Ritchie RH, Twigg SM, Cooper ME, Burrell LM (2003) A breaker of advanced glycation end products attenuates diabetes-induced myocardial structural changes. Circ Res 92(7):785–792. doi:10.1161/01.RES.0000065620.39919.20 PubMedCrossRefGoogle Scholar
  147. 147.
    Forbes JM, Yee LT, Thallas V, Lassila M, Candido R, Jandeleit-Dahm KA, Thomas MC, Burns WC, Deemer EK, Thorpe SR, Cooper ME, Allen TJ (2004) Advanced glycation end product interventions reduce diabetes-accelerated atherosclerosis. Diabetes 53(7):1813–1823PubMedCrossRefGoogle Scholar
  148. 148.
    Joshi D, Gupta R, Dubey A, Shiwalkar A, Pathak P, Gupta RC, Chauthaiwale V, Dutt C (2009) TRC4186, a novel AGE-breaker, improves diabetic cardiomyopathy and nephropathy in Ob-ZSF1 model of type 2 diabetes. J Cardiovasc Pharmacol 54(1):72–81. doi:10.1097/FJC.0b013e3181ac3a34 PubMedCrossRefGoogle Scholar
  149. 149.
    Pathak P, Gupta R, Chaudhari A, Shiwalkar A, Dubey A, Mandhare AB, Gupta RC, Joshi D, Chauthaiwale V (2008) TRC4149 a novel advanced glycation end product breaker improves hemodynamic status in diabetic spontaneously hypertensive rats. Eur J Med Res 13(8):388–398PubMedGoogle Scholar
  150. 150.
    Cheng G, Wang LL, Long L, Liu HY, Cui H, Qu WS, Li S (2007) Beneficial effects of C36, a novel breaker of advanced glycation endproducts cross-links, on the cardiovascular system of diabetic rats. Br J Pharmacol 152(8):1196–1206. doi:10.1038/sj.bjp.0707533 PubMedCrossRefGoogle Scholar
  151. 151.
    Kranstuber AL, del Rio C, Biesiadecki BJ, Hamlin RL, Ottobre J, Gyorke S, Lacombe VA (2012) Advanced glycation end product cross-link breaker attenuates diabetes-induced cardiac dysfunction by improving sarcoplasmic reticulum calcium handling. Frontiers Physiol 3:292. doi:10.3389/fphys.2012.00292. Epub 2012 July 19
  152. 152.
    Little WC, Zile MR, Kitzman DW, Hundley WG, O’Brien TX, Degroof RC (2005) The effect of alagebrium chloride (ALT-711), a novel glucose cross-link breaker, in the treatment of elderly patients with diastolic heart failure. J Card Fail 11(3):191–195PubMedCrossRefGoogle Scholar
  153. 153.
    Kalousova M, Skrha J, Zima T (2002) Advanced glycation end-products and advanced oxidation protein products in patients with diabetes mellitus. Physiol Res Academia Scientiarum Bohemoslovaca 51(6):597–604Google Scholar
  154. 154.
    Kostolanska J, Jakus V, Barak L (2009) Monitoring of early and advanced glycation in relation to the occurrence of microvascular complications in children and adolescents with type 1 diabetes mellitus. Physiol Res Academia Scientiarum Bohemoslovaca 58(4):553–561Google Scholar
  155. 155.
    Lapolla A, Piarulli F, Sartore G, Ceriello A, Ragazzi E, Reitano R, Baccarin L, Laverda B, Fedele D (2007) Advanced glycation end products and antioxidant status in type 2 diabetic patients with and without peripheral artery disease. Diabetes Care 30(3):670–676. doi:10.2337/dc06-1508 PubMedCrossRefGoogle Scholar
  156. 156.
    Kanauchi M, Nishioka H, Dohi K (2001) Serum levels of advanced glycosylation end products in diabetic nephropathy. Nephron 89(2):228–230. doi:46073 PubMedCrossRefGoogle Scholar
  157. 157.
    Perkins BA, Rabbani N, Weston A, Ficociello LH, Adaikalakoteswari A, Niewczas M, Warram J, Krolewski AS, Thornalley P (2012) Serum levels of advanced glycation endproducts and other markers of protein damage in early diabetic nephropathy in type 1 diabetes. PLoS ONE 7(4):e35655. doi:10.1371/journal.pone.0035655 PubMedCentralPubMedCrossRefGoogle Scholar
  158. 158.
    Kilhovd BK, Berg TJ, Birkeland KI, Thorsby P, Hanssen KF (1999) Serum levels of advanced glycation end products are increased in patients with type 2 diabetes and coronary heart disease. Diabetes Care 22(9):1543–1548PubMedCrossRefGoogle Scholar
  159. 159.
    Yoshida N, Okumura K, Aso Y (2005) High serum pentosidine concentrations are associated with increased arterial stiffness and thickness in patients with type 2 diabetes. Metabolism 54(3):345–350. doi:10.1016/j.metabol.2004.09.014 PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Vijaya Lakshmi Bodiga
    • 1
  • Sasidhar Reddy Eda
    • 2
  • Sreedhar Bodiga
    • 2
  1. 1.Department of BiotechnologyKrishna UniversityMachilipatnamIndia
  2. 2.Department of Biotechnology, Center for Biomedical ResearchKL UniversityVaddeswaramIndia

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