Endocrine

, Volume 43, Issue 3, pp 472–484 | Cite as

Methylglyoxal, obesity, and diabetes

Review

Abstract

Methylglyoxal (MG) is a highly reactive compound derived mainly from glucose and fructose metabolism. This metabolite has been implicated in diabetic complications as it is a strong AGE precursor. Furthermore, recent studies suggested a role for MG in insulin resistance and beta-cell dysfunction. Although several drugs have been developed in the recent years to scavenge MG and inhibit AGE formation, we are still far from having an effective strategy to prevent MG-induced mechanisms. This review summarizes the mechanisms of MG formation, detoxification, and action. Furthermore, we review the current knowledge about its implication on the pathophysiology and complications of obesity and diabetes.

Keywords

Diabetes Hyperglycemia Methylglyoxal 

References

  1. 1.
    C. Neuberg, Biochem. Z. 51, 484–508 (1913)Google Scholar
  2. 2.
    H. Dakin, H. Dudley, An enzyme concerned with the formation of hydroxy acids from ketonic aldehydes. J. Biol. Chem. 14, 423–431 (1913)Google Scholar
  3. 3.
    E. Case, R. Cook, The occurrence of pyruvic acid and methylglyoxal in muscle metabolism. Biochem. J. 25(4), 1319–1335 (1931)PubMedGoogle Scholar
  4. 4.
    F. Clift, R.P. Cook, A method of determination of some biologically important aldehydes and ketones, with special reference to pyruvic acid and methylglyoxal. Biochem. J. 26(6), 1788–1799 (1932)PubMedGoogle Scholar
  5. 5.
    A. McLellan, P.J. Thornalley, Glyoxalase activity in human red blood cells fractioned by age. Mech. Ageing Dev. 48(1), 63–71 (1989)PubMedCrossRefGoogle Scholar
  6. 6.
    P.J. Thornalley, Modification of the glyoxalase system in human red blood cells by glucose in vitro. Biochem. J. 254(3), 751–755 (1988)PubMedGoogle Scholar
  7. 7.
    T. Atkins, P. Thornally, Erythrocyte glyoxalase activity in genetically obese (ob/ob) and streptozotocin diabetic mice. Diabetes Res. 11(3), 125–129 (1989)PubMedGoogle Scholar
  8. 8.
    P.J. Thornalley, N. Hooper, P. Jennings, C. Florkowski, A. Jones, J. Lunec, A. Barnett, The human red blood cell glyoxalase system in diabetes mellitus. Diabetes Res. Clin. Pract. 7(2), 115–120 (1989)PubMedCrossRefGoogle Scholar
  9. 9.
    P.J. Thornalley, The glyoxalase system: new developments towards functional characterization of a metabolic pathway fundamental to biological life. Biochem. J. 269(1), 1–11 (1990)PubMedGoogle Scholar
  10. 10.
    A. McLellan, P.J. Thornalley, J. Benn, P. Sonksen, Glyoxalase system in clinical diabetes mellitus and correlation with diabetic complications. Clin. Sci. (Lond) 87(1), 21–29 (1994)Google Scholar
  11. 11.
    H. Odani, T. Shinzato, Y. Matsumoto, J. Usami, K. Maeda, Increase in three alpha, beta-dicarbonyl compound levels in human uremic plasma: specific in vivo determination of intermediates in advanced Maillard reaction. Biochem. Biophys. Res. Commun. 256(1), 89–93 (1999)PubMedCrossRefGoogle Scholar
  12. 12.
    M. Brownlee, The pathobiology of diabetic complications: a unifying mechanism. Diabetes 54(6), 1615–1625 (2005)PubMedCrossRefGoogle Scholar
  13. 13.
    W. Chan, H. Wu, N. Shao, Apoptotic signaling in methylglyoxal-treated human osteoblasts involves oxidative stress, c-Jun N-terminal kinase, caspase-3 and p21-activated kanse-2. J. Cell. Biochem. 100, 1056–1069 (2007)PubMedCrossRefGoogle Scholar
  14. 14.
    K. Nakayama, M. Nakayama, M. Iwabuchi, H. Terawaki, T. Sato, M. Kohno, S. Ito, Plasma alpha-oxoaldehyde levels in diabetic and nondiabetic chronic kidney disease patients. Am. J. Nephrol. 28(6), 871–878 (2008)PubMedCrossRefGoogle Scholar
  15. 15.
    D. Tan, Y. Wang, C. Lo, S. Sang, C. Ho, Methylglyoxal: its presence in beverages and potential scavengers. Ann. N. Y. Acad. Sci. 1126, 72–75 (2008)PubMedCrossRefGoogle Scholar
  16. 16.
    O. Lee, W. Bruce, Q. Dong, J. Bruce, R. Mehta, P. O’Brien, Fructose and carbonyl metabolites as endogenous toxins. Chem. Biol. Interact. 178(1–3), 332–339 (2009)PubMedCrossRefGoogle Scholar
  17. 17.
    J. Liu, R. Wang, K. Desai, L. Wu, Upregulation of aldolase B and overproduction of methylglyoxal in vascular tissues from rats with metabolic syndrome. Cardiovasc. Res. 92(3), 494–503 (2011)PubMedCrossRefGoogle Scholar
  18. 18.
    P. Yu, M. Wang, H. Fan, Y. Deng, D. Gubisne-Haberle, Involvement of SSAO-mediated deamination in adipose glucose transport and weight gain in obese diabetic KKAy mice. Am. J. Physiol. Endocrinol. Metab. 286(4), E634–E641 (2004)PubMedCrossRefGoogle Scholar
  19. 19.
    M. Barrand, B. Callingham, Solubilization and some properties of a semicarbazide-sensitive amine oxidase in brown adipose tissue of the rat. Biochem. J. 222, 467–475 (1984)PubMedGoogle Scholar
  20. 20.
    Y. Deng, P. Yu, Assessment of the deamination of aminoacetone, an endogenous substrate for semicarbazide-sensitive amine oxidase. Anal. Biochem. 270, 97–102 (1999)PubMedCrossRefGoogle Scholar
  21. 21.
    Z. Turk, M. Cavlović-Naglić, N. Turk, Relationship of methylglyoxal-adduct biogenesis to LDL and triglyceride levels in diabetics. Life Sci. 89(13–14), 485–490 (2011)PubMedCrossRefGoogle Scholar
  22. 22.
    N. Ahmed, B. Mirshekar-Syahkal, L. Kennish, N. Karachalias, R. Babaei-Jadidi, P.J. Thornalley, Assay of advanced glycation endproducts in selected beverages and food by liquid chromatography with tandem mass spectrometric detection. Mol. Nutr. Food Res. 49(7), 691–699 (2005)PubMedCrossRefGoogle Scholar
  23. 23.
    A. Negre-Salvayre, R. Salvayre, N. Augé, R. Pamplona, M. Portero-Otín, Hyperglycemia and glycation in diabetic complications. Antioxid. Redox Signal. 11(12), 3071–3109 (2009)PubMedCrossRefGoogle Scholar
  24. 24.
    A. Stirban, M. Negrean, C. Götting, B. Stratmann, T. Gawlowski, M. Mueller-Roesel, K. Kleesiek, T. Koschinsky, D. Tschoepe, Leptin decreases postprandially in people with type 2 diabetes, an effect reduced by the cooking method. Horm. Metab. Res. 40(12), 896–900 (2008)PubMedCrossRefGoogle Scholar
  25. 25.
    E. Marceau, V.A. Yaylayan, Profiling of alpha-dicarbonyl content of commercial honeys from different botanical origins: identification of 3,4-dideoxyglucoson-3-ene (3,4-DGE) and related compounds. Agric. Food Chem. 57(22), 10837–10844 (2009)CrossRefGoogle Scholar
  26. 26.
    R. Zhao, A. Lee, J.P. Abbatt, Investigation of aqueous-phase photooxidation of glyoxal and methylglyoxal by aerosol chemical ionization mass spectrometry: observation of hydroxyhydroperoxide formation. J. Phys. Chem. A. 116(24), 6253–6263 (2012)PubMedCrossRefGoogle Scholar
  27. 27.
    S. Gensberger, S. Mittelmaier, M. Glomb, M. Pischetsrieder, Identification and quantification of six major α-dicarbonyl process contaminants in high-fructose corn syrup. Anal. Bioanal. Chem. 403(10), 2923–2931 (2012)PubMedCrossRefGoogle Scholar
  28. 28.
    R. Spanneberg, G. Salzwedel, M. Glomb, Formation of early and advanced Maillard reaction products correlates to the ripening of cheese. J. Agric. Food Chem. 60(2), 600–607 (2012)PubMedCrossRefGoogle Scholar
  29. 29.
    J. Wang, T. Chang, Methylglyoxal content in drinking coffee as a cytotoxic factor. J. Food Sci. 75(6), H167–H171 (2010)PubMedCrossRefGoogle Scholar
  30. 30.
    A. Goldin, J. Beckman, A. Schmidt, M. Creager, Advanced glycation end products: sparking the development of diabetic vascular injury. Circulation 114, 597–605 (2006)PubMedCrossRefGoogle Scholar
  31. 31.
    M. Xue, N. Rabbani, P. Thornalley, Glyoxalase in ageing. Semin. Cell Dev. Biol. 22(3), 293–301 (2011)PubMedCrossRefGoogle Scholar
  32. 32.
    P. Thornalley, N. Rabbani, Glyoxalase in tumourigenesis and multidrug resistance. Semin. Cell Dev. Biol. 22(3), 318–325 (2011)PubMedCrossRefGoogle Scholar
  33. 33.
    S. Hoon, M. Gebbia, M. Costanzo, R. Davis, G. Giaever, C. Nislow, A global perspective of the genetic basis for carbonyl stress resistance. G3 (Bethesda) 1(3), 219–231 (2011)CrossRefGoogle Scholar
  34. 34.
    M. Lin, H. Chen, T. Liao, T. Huang, C. Chen, J. Lee, Determination of time-dependent accumulation of d-lactate in the streptozotocin-induced diabetic rat kidney by column-switching HPLC with fluorescence detection. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 879(29), 3214–3219 (2011)PubMedCrossRefGoogle Scholar
  35. 35.
    Y. Kondoh, M. Kawase, M. Hirata, S. Ohmori, Carbon sources for d-lactate formation in rat liver. J. Biochem. 115(3), 590–595 (1994)PubMedGoogle Scholar
  36. 36.
    T. Fujisawa, S. Akagi, M. Kawase, M. Yamamoto, S. Ohmori, d-lactate metabolism in starved Octopus ocellatus. J. Exp. Zool. A Comp. Exp. Biol. 303(6), 489–496 (2005)PubMedGoogle Scholar
  37. 37.
    N. Rabbani, P.J. Thornalley, Glyoxalase in diabetes, obesity and related disorders. Semin. Cell Dev. Biol. 22(3), 309–317 (2011)PubMedCrossRefGoogle Scholar
  38. 38.
    S. Falone, A. D’Alessandro, A. Mirabilio, G. Petruccelli, M. Cacchio, C. Di Ilio, S. Di Loreto, F. Amicarelli, Long term running biphasically improves methylglyoxal-related metabolism, redox homeostasis and neurotrophic support within adult mouse brain cortex. PLoS One 7(2), e31401 (2012)PubMedCrossRefGoogle Scholar
  39. 39.
    K. Kim, Y. Kim, D. Jung, J. Lee, J. Kim, Increased glyoxalase I levels inhibit accumulation of oxidative stress and an advanced glycation end product in mouse mesangial cells cultured in high glucose. Exp. Cell Res. 318(2), 152–159 (2012)PubMedCrossRefGoogle Scholar
  40. 40.
    A. Berner, O. Brouwers, R. Pringle, I. Klaassen, L. Colhoun, C. McVicar, S. Brockbank, J. Curry, T. Miyata, M. Brownlee, R. Schlingemann, C. Schalkwijk, A.W. Stitt, Protection against methylglyoxal-derived AGEs by regulation of glyoxalase 1 prevents retinal neuroglial and vasodegenerative pathology. Diabetologia 55(3), 845–854 (2012)PubMedCrossRefGoogle Scholar
  41. 41.
    R. Inagi, T. Kumagai, T. Fujita, M. Nangaku, The role of glyoxalase system in renal hypoxia. Adv. Exp. Med. Biol. 662, 49–55 (2010)PubMedCrossRefGoogle Scholar
  42. 42.
    M. Jack, J. Ryals, D. Wright, Protection from diabetes-induced peripheral sensory neuropathy—a role for elevated glyoxalase I? Exp. Neurol. 234(1), 62–69 (2012)PubMedCrossRefGoogle Scholar
  43. 43.
    T. Fleming, J. Cuny, G. Nawroth, Z. Djuric, P. Humpert, M. Zeier, A. Bierhaus, P. Nawroth, Is diabetes an acquired disorder of reactive glucose metabolites and their intermediates? Diabetologia 55(4), 1151–1155 (2012)PubMedCrossRefGoogle Scholar
  44. 44.
    A. Ceriello, M. Ihnat, J. Thorpe, The “metabolic memory”: is more than just tight glucose control necessary to prevent diabetic complications? J. Clin. Endocrinol. Metab. 94(2), 410–415 (2009)PubMedCrossRefGoogle Scholar
  45. 45.
    H. Odani, J. Asami, A. Ishii, K. Oide, T. Sudo, A. Nakamura, N. Miyata, N. Otsuka, K. Maeda, J. Nakagawa, Suppression of renal alpha-dicarbonyl compounds generated following ureteral obstruction by kidney specific alpha-dicarbonyl/l-xylulose reductase. Ann. N. Y. Acad. Sci. 1126, 320–324 (2008)PubMedCrossRefGoogle Scholar
  46. 46.
    N. Rabbani, P.J. Thornalley, Methylglyoxal, glyoxalase 1 and the dicarbonyl proteome. Amino Acids 42(4), 1133–1142 (2012)PubMedCrossRefGoogle Scholar
  47. 47.
    D. Li, M. Ferrari, E. Ellis, Human aldo-keto reductase AKR7A2 protects against the cytotoxicity and mutagenicity of reactive aldehydes and lowers intracellular reactive oxygen species in hamster V79-4 cells. Chem. Biol. Interact. 195(1), 25–34 (2012)PubMedCrossRefGoogle Scholar
  48. 48.
    S. Baba, O. Barski, Y. Ahmed, T. O’Toole, D.J. Conklin, A. Bhatnagar, S. Srivastava, Reductive metabolism of AGE precursors: a metabolic route for preventing AGE accumulation in cardiovascular tissue. Diabetes 58(11), 2486–2497 (2009)PubMedCrossRefGoogle Scholar
  49. 49.
    R. Narawongsanont, S. Kabinpong, B. Auiyawong, C. Tantitadapitak, Cloning and characterization of AKR4C14, a rice aldoketo reductase from Thai Jasmine rice. Protein J. 31(1), 35–42 (2012)PubMedCrossRefGoogle Scholar
  50. 50.
    S. Baba, J. Hellmann, S. Srivastava, A. Bhatnagar, Aldose reductase (AKR1B3) regulates the accumulation of advanced glycosylation end products (AGEs) and the expression of AGE receptor (RAGE). Chem. Biol. Interact. 191(1–3), 357–363 (2011)PubMedCrossRefGoogle Scholar
  51. 51.
    M. Laga, A. Cottyn, F. van Herreweghe, W. Vanden Berghe, G. Haegeman, P. Van Oostveldt, J. Vandekerckhove, K. Vancompernolle, Methylglyoxal suppresses TNF-α-induced NF-κB activation by inhibiting NF-κB DNA-binding. Biochem. Pharmacol. 74(4), 579–589 (2007)PubMedCrossRefGoogle Scholar
  52. 52.
    S. Grimm, M. Horlacher, B. Catalgol, A. Hoehn, T. Reinheckel, T. Grune, Cathepsins D and L reduce the toxicity of advanced glycation end products. Free Radic. Biol. Med. 52(6), 1011–1023 (2012)PubMedCrossRefGoogle Scholar
  53. 53.
    C. Bento, F. Marques, R. Fernandes, P. Pereira, Methylglyoxal alters the function and stability of critical components of the protein quality control. PLoS One 5(9), e13007 (2010)PubMedCrossRefGoogle Scholar
  54. 54.
    K. Nakajou, S. Horiuchi, M. Sakai, N. Haraguchi, M. Tanaka, M. Takeya, M. Otagiri, Renal clearance of glycolaldehyde- and methylglyoxal-modified proteins in mice is mediated by mesangial cells through a class A scavenger receptor (SR-A). Diabetologia 48(2), 317–327 (2005)PubMedCrossRefGoogle Scholar
  55. 55.
    S. Chetyrkin, W. Zhang, B. Hudson, A. Serianni, P. Voziyan, Pyridoxamine protects proteins from functional damage by 3-deoxyglucosone: mechanism of action of pyridoxamine. Biochemistry 47(3), 997–1006 (2008)PubMedCrossRefGoogle Scholar
  56. 56.
    J. Kim, O. Kim, C. Kim, E. Sohn, K. Jo, J. Kim, Accumulation of argpyrimidine, a methylglyoxal-derived advanced glycation end product, increases apoptosis of lens epithelial cells both in vitro and in vivo. Exp. Mol. Med. 44(2), 167–175 (2012)PubMedCrossRefGoogle Scholar
  57. 57.
    X. Fan, L. Xiaoqin, B. Potts, C. Strauch, I. Nemet, V. Monnier, Topical application of l-arginine blocks advanced glycation by ascorbic acid in the lens of hSVCT2 transgenic mice. Mol. Vis. 17, 2221–2227 (2011)PubMedGoogle Scholar
  58. 58.
    L. Lv, X. Shao, H. Chen, C. Ho, S. Sang, Genistein inhibits advanced glycation end product formation by trapping methylglyoxal. Chem. Res. Toxicol. 24(4), 579–586 (2011)PubMedCrossRefGoogle Scholar
  59. 59.
    A. Dhar, K. Desai, L. Wu, Alagebrium attenuates acute methylglyoxal-induced glucose intolerance in Sprague-Dawley rats. Br. J. Pharmacol. 159(1), 166–175 (2010)PubMedCrossRefGoogle Scholar
  60. 60.
    H. Liu, H. Liu, W. Wang, C. Khoo, J. Taylor, L. Gu, Cranberry phytochemicals inhibit glycation of human hemoglobin and serum albumin by scavenging reactive carbonyls. Food Funct. 2(8), 475–482 (2011)PubMedCrossRefGoogle Scholar
  61. 61.
    H. Liu, L. Gu, Phlorotannins from brown algae (Fucus vesiculosus) inhibited the formation of advanced glycation endproducts by scavenging reactive carbonyls. J. Agric. Food Chem. 60(5), 1326–1334 (2012)PubMedCrossRefGoogle Scholar
  62. 62.
    M. Lu, R. Wang, X. Song, R. Chibbar, X. Wang, L. Wu, Q. Meng, Dietary soy isoflavones increase insulin secretion and prevent the development of diabetic cataracts in streptozotocin-induced diabetic rats. Nutr. Res. 28(7), 464–471 (2008)PubMedCrossRefGoogle Scholar
  63. 63.
    P. Maher, R. Dargusch, J. Ehren, S. Okada, K. Sharma, D. Schubert, Fisetin lowers methylglyoxal dependent protein glycation and limits the complications of diabetes. PLoS One 6(6), e21226 (2011)PubMedCrossRefGoogle Scholar
  64. 64.
    Z. Wang, C. Hsu, C. Huang, M. Yin, Anti-glycative effects of oleanolic acid and ursolic acid in kidney of diabetic mice. Eur. J. Pharmacol. 628(1–3), 255–260 (2010)PubMedCrossRefGoogle Scholar
  65. 65.
    P. Muthenna, C. Akileshwari, G. Reddy, Ellagic acid, a new antiglycating agent: its inhibition of Nϵ-(carboxymethyl)lysine. Biochem. J. 442(1), 221–230 (2012)PubMedCrossRefGoogle Scholar
  66. 66.
    S. Taneda, K. Honda, K. Tomidokoro, K. Uto, K. Nitta, H. Oda, Eicosapentaenoic acid restores diabetic tubular injury through regulating oxidative stress and mitochondrial apoptosis. Am. J. Physiol. Renal Physiol. 299(6), F1451–F1461 (2010)PubMedCrossRefGoogle Scholar
  67. 67.
    X. Jia, D.J. Olson, A.R. Ross, L. Wu, Structural and functional changes in human insulin induced by methylglyoxal. FASEB J. 20, 1555–1557 (2006)PubMedCrossRefGoogle Scholar
  68. 68.
    Y. Gao, Y. Wang, Site-selective modifications of arginine residues in human hemoglobin induced by methylglyoxal. Biochemistry 45, 15654–15660 (2006)PubMedCrossRefGoogle Scholar
  69. 69.
    A. Cantero, M. Portero-Otin, V. Ayala, N. Auge, M. Sanson, M. Elbaz, J. Thiers, R. Pamplona, R. Salvayre, A. Negre-Salvayre, Methylglyoxal induces advanced glycation end product (AGEs) formation and dysfunction of PDGF receptor-beta: implications for diabetic atherosclerosis. FASEB J. 21, 3096–3106 (2007)PubMedCrossRefGoogle Scholar
  70. 70.
    A. Biswas, B. Wang, M. Miyagi, R.H. Nagaraj, Effect of methylglyoxal modification on stress-induced aggregation of client proteins and their chaperoning by human alphaA crystallin. Biochem. J. 409, 771–777 (2008)PubMedCrossRefGoogle Scholar
  71. 71.
    M.U. Ahmed, F. Brinkmann, T.P. Degenhardt, S. Thorpe, J. Baynes, N-epsilon-(carboxyethyl)lysine, a product of the chemical modification of proteins by methylglyoxal, increases with age in human lens proteins. Biochem. J. 324, 565–570 (1997)PubMedGoogle Scholar
  72. 72.
    N. Rabbani, P. Thornalley, The dicarbonyl proteome: proteins susceptible to dicarbonyl glycation at functional sites in health, aging, and disease. Ann. N. Y. Acad. Sci. 1126, 124–127 (2008)PubMedCrossRefGoogle Scholar
  73. 73.
    R. Nagaraj, A. Panda, S. Shanthakumar, P. Santhoshkumar, N. Pasupuleti, B. Wang, A. Biswas, Hydroimidazolone modification of the conserved Arg12 in small heat shock proteins: studies on the structure and chaperone function using mutant mimics. PLoS One 7(1), e30257 (2012)PubMedCrossRefGoogle Scholar
  74. 74.
    T. Kumagai, M. Nangaku, I. Kojima, R. Nagai, J. Ingelfinger, T. Miyata, T. Fujita, R. Inagi, Glyoxalase I overexpression ameliorates renal ischemic-reperfusion injury in rats. Am. J. Physiol. Renal Physiol. 296, F912–F921 (2009)PubMedCrossRefGoogle Scholar
  75. 75.
    P. Matafome, D. Santos-Silva, J. Crisóstomo, T. Rodrigues, L. Rodrigues, C. Sena, P. Pereira, R. Seiça, Methylglyoxal causes structural and functional alterations in adipose tissue independently of obesity. Arch. Physiol. Biochem. 118(2), 58–68 (2012)PubMedCrossRefGoogle Scholar
  76. 76.
    J.W. Baynes, The Maillard hypothesis on aging: time to focus on DNA. Ann. N. Y. Acad. Sci. 959, 360–367 (2002)PubMedCrossRefGoogle Scholar
  77. 77.
    M.J. Roberts, G.T. Wondrak, D.C. Laurean, M.K. Jacobson, E. Jacobson, DNA damage by carbonyl stress in human skin cells. Mutat. Res. 522(1–2), 45–56 (2003)PubMedGoogle Scholar
  78. 78.
    P.J. Thornalley, Protecting the genome: defence against nucleotide glycation and emerging role of glyoxalase I overexpression in multidrug resistance in cancer chemotherapy. Biochem. Soc. Trans. 31(Pt 6), 1372–1377 (2003)PubMedCrossRefGoogle Scholar
  79. 79.
    A. Guerin-Dubourg, A. Catan, E. Bourdon, P. Rondeau, Structural modifications of human albumin in diabetes. Diabetes Metab. 38(2), 171–178 (2012)PubMedCrossRefGoogle Scholar
  80. 80.
    S. Yamagishi, Y. Inagaki, T. Okamoto, S. Amano, K. Koga, M. Takeuchi, Advanced glycation end products inhibit de novo protein synthesis and induce TGF-beta overexpression in proximal tubular cells. Kidney Int. 63(2), 464–473 (2003)PubMedCrossRefGoogle Scholar
  81. 81.
    T. Lund, A. Svindland, M. Pepaj, A. Jensen, J. Berg, B. Kilhovd, K. Hanssen, Fibrin(ogen) may be an important target for methylglyoxal-derived AGE modification in elastic arteries of humans. Diab. Vasc. Dis. Res. 8(4), 284–294 (2011)PubMedCrossRefGoogle Scholar
  82. 82.
    M. Mukohda, M. Okada, Y. Hara, H. Yamawaki, Exploring mechanisms of diabetes-related macrovascular complications: role of methylglyoxal, a metabolite of glucose on regulation of vascular contractility. J. Pharmacol. Sci. 118(3), 303–310 (2012)PubMedCrossRefGoogle Scholar
  83. 83.
    M. Mukohda, T. Morita, M. Okada, Y. Hara, H. Yamawaki, Long-term methylglyoxal treatment impairs smooth muscle contractility in organ-cultured rat mesenteric artery. Pharmacol. Res. 65(1), 91–99 (2012)PubMedCrossRefGoogle Scholar
  84. 84.
    A. Pozzi, R. Zent, S. Chetyrkin, C. Borza, N. Bulus, P. Chuang, D. Chen, B. Hudson, P. Voziyan, Modification of collagen IV by glucose or methylglyoxal alters distinct mesangial cell functions. J. Am. Soc. Nephrol. 20(10), 2119–2125 (2009)PubMedCrossRefGoogle Scholar
  85. 85.
    V. Pedchenko, S. Chetyrkin, P. Chuang, A. Ham, M. Sallem, P. Mathieson, B. Hudson, P. Voziyan, Mechanisms of perturbation of integrin-mediated cell-matrix interactions by reactive carbonyl compounds and its implication for pathogenesis of diabetic nephropathy. Diabetes 54, 2952–2960 (2005)PubMedCrossRefGoogle Scholar
  86. 86.
    D. Yao, T. Taguchi, T. Matsumura, R. Pestell, D. Edelstein, I. Giardino, G. Suske, N. Rabbani, P. Thornalley, V. Sarthy, H. Hammes, M. Brownlee, High glucose increases angiopoietin-2 transcription in microvascular endothelial cells through methylglyoxal modification of mSin3A. J. Biol. Chem. 282, 31038–31045 (2007)PubMedCrossRefGoogle Scholar
  87. 87.
    H. Thangarajah, D. Yao, E. Chang, Y. Shi, L. Jazayeri, I. Vial, R. Galiano, X. Du, R. Grogan, M. Galvez, M. Januszyk, M. Brownlee, G. Gurtner, The molecular basis for impaired hypoxia-induced VEGF expression in diabetic tissues. Proc. Natl. Acad. Sci. USA 106(32), 13505–13510 (2009)PubMedCrossRefGoogle Scholar
  88. 88.
    C. Bento, R. Fernandes, J. Ramalho, C. Marques, F. Shang, A. Taylor, P. Pereira, The chaperone-dependent ubiquitin ligase chip targets HIF-1α for degradation in the presence of methylglyoxal. PLoS One 5(11), e15062 (2010)PubMedCrossRefGoogle Scholar
  89. 89.
    C. Bento, R. Fernandes, P. Matafome, C. Sena, R. Seiça, P. Pereira, Methylglyoxal-induced imbalance in the ratio of vascular endothelial growth factor to angiopoietin 2 secreted by retinal pigment epithelial cells leads to endothelial dysfunction. Exp. Physiol. 95(9), 955–970 (2010)PubMedGoogle Scholar
  90. 90.
    D. Vander Jagt, R. Hassebrook, L. Hunsaker, W. Brown, R. Royer, 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. 130–132, 549–562 (2001)PubMedCrossRefGoogle Scholar
  91. 91.
    G. Tang, Y. Minemoto, B. Dibling, N. Purcell, Z. Li, M. Karin, A. Lin, Inhibition of JNK activation through NF-κB target genes. Nature 414(6861), 6313–6317 (2001)CrossRefGoogle Scholar
  92. 92.
    M. Queisser, D. Yao, S. Geisler, H. Hammes, G. Lochnit, E. Schleicher, M. Brownlee, K. Preissner, Hyperglycemia impairs proteasome function by methylglyoxal. Diabetes 59(3), 670–678 (2010)PubMedCrossRefGoogle Scholar
  93. 93.
    A.K. Padival, J. Crabb, R. Nagaraj, Methylglyoxal modifies heat shock protein 27 in glomerular mesangial cells. FEBS Lett. 551(1–3), 113–118 (2003)PubMedCrossRefGoogle Scholar
  94. 94.
    K. Desai, L. Wu, Free radical generation by methylglyoxal in tissues. Drug Metabol. Drug Interact. 23, 151–173 (2008)PubMedCrossRefGoogle Scholar
  95. 95.
    L. Wu, B. Juurlink, Increased methylglyoxal and oxidative stress in hypertensive rat vascular smooth muscle cells. Hypertension 39, 809–814 (2002)PubMedCrossRefGoogle Scholar
  96. 96.
    T. Chang, R. Wang, L. Wu, Methylglyoxal-induced nitric oxide and peroxynitrite production in vascular smooth muscle cells. Free Radic. Biol. Med. 38, 286–293 (2005)PubMedCrossRefGoogle Scholar
  97. 97.
    A. Dhar, K. Desai, M. Kazachmov, P. Yu, L. Wu, Methylglyoxal production in vascular smooth muscle cells from different metabolic precursors. Metabolism 57, 1211–1220 (2008)PubMedCrossRefGoogle Scholar
  98. 98.
    C. Sena, P. Matafome, J. Crisóstomo, L. Rodrigues, R. Fernandes, P. Pereira, R. Seiça, Methylglyoxal promotes oxidative stress and endothelial dysfunction. Pharmacol. Res. 65(5), 497–506 (2012)PubMedCrossRefGoogle Scholar
  99. 99.
    R. Ward, K. McLeish, Methylglyoxal: a stimulus to neutrophil oxygen radical production in chronic renal failure? Nephrol. Dial. Transplant. 19, 1702–1707 (2004)PubMedCrossRefGoogle Scholar
  100. 100.
    G. Leoncini, M. Poggi, Effects of methylglyoxal on platelet hydrogen peroxide accumulation, aggregation and release reaction. Cell Biochem. Funct. 14, 89–95 (1996)PubMedGoogle Scholar
  101. 101.
    M.P. Kalapos, A. Littauer, H. de Groot, Has reactive oxygen a role in methylglyoxal toxicity? A study on cultured rat hepatocytes. Arch. Toxicol. 67, 369–372 (1993)PubMedCrossRefGoogle Scholar
  102. 102.
    S. Di Loreto, V. Caracciolo, S. Colafarina, P. Sebastiani, A. Gasbarri, F. Amicarelli, Methylglyoxal induces oxidative stress-dependent cell injury and up-regulation of interleukin-1beta and nerve growth factor in cultured hippocampal neuronal cells. Brain Res. 1006, 157–167 (2004)PubMedCrossRefGoogle Scholar
  103. 103.
    A. Akhand, K. Hossain, H. Mitsui, M. Kato, T. Miyata, R. Inagi, J. Du, K. Takeda, Y. Kawamoto, H. Suzuki, K. Kurokawa, I. Nakashima, Glyoxal and methylglyoxal trigger distinct signals for map family kinases and caspase activation in human endothelial cells. Free Radic. Biol. Med. 31, 20–30 (2001)PubMedCrossRefGoogle Scholar
  104. 104.
    A. Uriuhara, S. Miyata, B. Liu, H. Miyazaki, H. Kusunoki, H. Kojima, Y. Yamashita, K. Suzuki, K. Inaba, M. Kasuga, Methylglyoxal induces prostaglandin E2 production in rat mesangial cells. Kobe J. Med. Sci. 53(6), 305–315 (2008)PubMedGoogle Scholar
  105. 105.
    S. Kikuchi, K. Shinpo, F. Moriwaka, Z. Makita, T. Miyata, K. Tashiro, Neurotoxicity of methylglyoxal and 3-deoxyglucosone on cultured cortical neurons: synergism between glycation and oxidative stress, possibly involved in neurodegenerative diseases. J. Neurosci. Res. 57, 280–289 (1999)PubMedCrossRefGoogle Scholar
  106. 106.
    F. Amicarelli, S. Colafarina, F. Cattani, A. Cimini, C. Di Ilio, M. Ceru, M. Miranda, Scavenging system efficiency is crucial for cell resistance to ROS-mediated methylglyoxal injury. Free Radic. Biol. Med. 35, 856–871 (2003)PubMedCrossRefGoogle Scholar
  107. 107.
    C. Paget, M. Lecomte, D. Ruggiero, N. Wiernsperger, M. Lagarde, Modification of enzymatic antioxidants in retinal microvascular cells by glucose or advanced glycation end products. Free. Radic. Biol. Med. 25, 121–129 (1998)PubMedCrossRefGoogle Scholar
  108. 108.
    H. Wang, J. Liu, L. Wu, Methylglyoxal-induced mitochondrial dysfunction in vascular smooth muscle cells. Biochem. Pharmacol. 77, 1709–1716 (2009)PubMedCrossRefGoogle Scholar
  109. 109.
    K. Desai, T. Chang, H. Wang, A. Banigesh, A. Dhar, J. Liu, A. Untereiner, L. Wu, Oxidative stress and aging: is methylglyoxal the hidden enemy? Can. J. Physiol. Pharmacol. 88, 273–284 (2010)PubMedCrossRefGoogle Scholar
  110. 110.
    D. Yao, M. Brownlee, Hyperglycemia-induced reactive oxygen species increase expression of the receptor for advanced glycation end products (RAGE) and RAGE ligands. Diabetes 59, 249–255 (2010)PubMedCrossRefGoogle Scholar
  111. 111.
    S. Yan, R. Ramasamy, Y. Naka, A. Schmidt, Glycation, inflammation, and RAGE: a scaffold for the macrovascular complications of diabetes and beyond. Circ. Res. 93(12), 1159–1169 (2003)PubMedCrossRefGoogle Scholar
  112. 112.
    R. Ramasamy, S. Yan, A. Schmidt, Advanced glycation endproducts: from precursors to RAGE: round and round we go. Amino Acids 42(4), 1151–1161 (2012)PubMedCrossRefGoogle Scholar
  113. 113.
    H. Ueno, H. Koyama, T. Shoji, M. Monden, S. Fukumoto, S. Tanaka, Y. Otsuka, Y. Mima, T. Morioka, K. Mori, A. Shioi, H. Yamamoto, M. Inaba, Y. Nishizawa, Receptor for advanced glycation end products (RAGE) regulation of adiposity and adiponectin is associated with atherogenesis in apoE deficient mouse. Atherosclerosis 211(2), 431–436 (2010)PubMedCrossRefGoogle Scholar
  114. 114.
    B. Leuner, M. Max, K. Thamm, C. Kausler, Y. Yakobus, A. Bierhaus, S. Sel, B. Hofmann, R. Silber, A. Simm, N. Nass, RAGE influences obesity in mice. Effects of the presence of RAGE on weight gain, AGE accumulation, and insulin levels in mice on a high fat diet. Z. Gerontol. Geriatr. 45(2), 102–108 (2012)PubMedCrossRefGoogle Scholar
  115. 115.
    Y. Hattori, H. Kakishita, K. Akimoto, M. Matsumura, K. Kasai, Glycated serum albumin-induced vascular smooth muscle cell proliferation through activation of the mitogen-activated protein kinase/extracellular signal-regulated kinase pathway by protein kinase C. Biochem. Biophys. Res. Commun. 281(4), 891–896 (2001)PubMedCrossRefGoogle Scholar
  116. 116.
    C. Lu, J. He, W. Cai, H. Liu, L. Zhu, H. Vlassara, Advanced glycation endproduct (AGE) receptor 1 is a negative regulator of the inflammatory response to AGE in mesangial cells. Proc. Natl. Acad. Sci. USA 101(32), 11767–11772 (2004)PubMedCrossRefGoogle Scholar
  117. 117.
    W. Cai, J.C. He, L. Zhu, X. Chen, G. Striker, H. Vlassara, AGE-receptor-1 counteracts cellular oxidant stress induced by AGEs via negative regulation of p66shc-dependent FKHRL1 phosphorylation. Am. J. Physiol. Cell Physiol. 294(1), C145–C152 (2008)PubMedCrossRefGoogle Scholar
  118. 118.
    W. Cai, M. Torreggiani, L. Zhu, X. Chen, J. He, G. Striker, H. Vlassara, AGER1 regulates endothelial cell NADPH oxidase-dependent oxidant stress via PKC-delta: implications for vascular disease. Am. J. Physiol. Cell Physiol. 298(3), C624–C634 (2010)PubMedCrossRefGoogle Scholar
  119. 119.
    J. Skrha Jr, J. Gáll, R. Buchal, E. Sedláčková, J. Pláteník, Glucose and its metabolites have distinct effects on the calcium-induced mitochondrial permeability transition. Folia Biol. (Praha) 57(3), 96–103 (2011)Google Scholar
  120. 120.
    A. Remor, F. de Matos, K. Ghisoni, T. da Silva, G. Eidt, M. Búrigo, A. de Bem, P. Silveira, A. de León, M. Sanchez, A. Hohl, V. Glaser, C. Gonçalves, A. Quincozes-Santos, R. Borba Rosa, A. Latini, Differential effects of insulin on peripheral diabetes-related changes in mitochondrial bioenergetics: involvement of advanced glycosylated end products. Biochim. Biophys. Acta. 1812(11), 1460–1471 (2011)PubMedCrossRefGoogle Scholar
  121. 121.
    B. Liu, S. Miyata, Y. Hirota, S. Higo, H. Miyazaki, M. Fukunaga, Y. Hamada, S. Ueyama, O. Muramoto, A. Uriuhara, M. Kasuga, Methylglyoxal induces apoptosis through activation of p38 mitogen-activated protein kinase in rat mesangial cells. Kidney Int. 63(3), 947–957 (2003)PubMedCrossRefGoogle Scholar
  122. 122.
    C. Ho, P. Lee, W. Huang, Y. Hsu, C. Lin, J. Wang, Methylglyoxal-induced fibronectin gene expression through Ras-mediated NADPH oxidase activation in renal mesangial cells. Nephrology (Carlton) 12(4), 348–356 (2007)CrossRefGoogle Scholar
  123. 123.
    J. Kim, O. Kim, C. Kim, N. Kim, J. Kim, Cytotoxic role of methylglyoxal in rat retinal pericytes: involvement of a nuclear factor-kappaB and inducible nitric oxide synthase pathway. Chem. Biol. Interact. 188(1), 86–93 (2010)PubMedCrossRefGoogle Scholar
  124. 124.
    M. Kalapos, The tandem of free radicals and methylglyoxal. Chem. Biol. Interact. 171(3), 251–271 (2008)PubMedCrossRefGoogle Scholar
  125. 125.
    J. Du, S. Cai, H. Suzuki, A. Akhand, X. Ma, Y. Takagi, T. Miyata, I. Nakashima, F. Nagase, Involvement of MEKK1/ERK/P21Waf1/Cip1 signal transduction pathway in inhibition of IGF-I-mediated cell growth response by methylglyoxal. J. Cell. Biochem. 88(6), 1235–1246 (2003)PubMedCrossRefGoogle Scholar
  126. 126.
    C. Schalkwijk, O. Brouwers, C. Stehouwer, Modulation of insulin action by advanced glycation endproducts: a new player in the field. Horm. Metab. Res. 40(9), 614–619 (2008)PubMedCrossRefGoogle Scholar
  127. 127.
    A. Riboulet-Chavey, A. Pierron, I. Durand, J. Murdaca, J. Giudicelli, E. Van Obberghen, Methylglyoxal impairs the insulin signaling pathways independently of the formation of intracellular reactive oxygen species. Diabetes 55(5), 1289–1299 (2006)PubMedCrossRefGoogle Scholar
  128. 128.
    X. Jia, L. Wu, Accumulation of endogenous methylglyoxal impaired insulin signaling in adipose tissue of fructose-fed rats. Mol. Cell. Biochem. 306, 133–139 (2007)PubMedCrossRefGoogle Scholar
  129. 129.
    A. Dhar, I. Dhar, B. Jiang, K. Desai, L. Wu, Chronic methylglyoxal infusion by minipump causes pancreatic beta-cell dysfunction and induces type 2 diabetes in Sprague-Dawley rats. Diabetes 60(3), 899–908 (2011)PubMedCrossRefGoogle Scholar
  130. 130.
    Q. Guo, T. Mori, Y. Jiang, C. Hu, Y. Osaki, Y. Yoneki, Y. Sun, T. Hosoya, A. Kawamata, S. Ogawa, M. Nakayama, T. Miyata, S. Ito, Methylglyoxal contributes to the development of insulin resistance and salt sensitivity in Sprague-Dawley rats. J. Hypertens. 27(8), 1664–1671 (2009)PubMedCrossRefGoogle Scholar
  131. 131.
    S. Hofmann, H. Dong, Z. Li, W. Cai, J. Altomonte, S. Thung, F. Zeng, E. Fisher, H. Vlassara, Improved insulin sensitivity is associated with restricted intake of dietary glycoxidation products in the db/db mouse. Diabetes 51(7), 2082–2089 (2002)PubMedCrossRefGoogle Scholar
  132. 132.
    F. Fiory, A. Lombardi, C. Miele, J. Giudicelli, F. Beguinot, E. Van Obberghen, Methylglyoxal impairs insulin signalling and insulin action on glucose-induced insulin secretion in the pancreatic beta cell line INS-1E. Diabetologia 54(11), 2941–2952 (2011)PubMedCrossRefGoogle Scholar
  133. 133.
    L. Cook, J. Davies, A. Yates, A. Elliott, J. Lovell, J. Joule, P. Pemberton, P.J. Thornalley, L. Best, Effects of methylglyoxal on rat pancreatic beta-cells. Biochem. Pharmacol. 55(9), 1361–1367 (1998)PubMedCrossRefGoogle Scholar
  134. 134.
    J.W. Baynes, S. Thorpe, Glycoxidation and lipoxidation in atherogenesis. Free Radic. Biol. Med. 28, 1708–1716 (2000)PubMedCrossRefGoogle Scholar
  135. 135.
    T. Chang, L. Wu, Methylglyoxal, oxidative stress, and hypertension. Can. J. Physiol. Pharmacol. 84, 1229–1238 (2006)PubMedCrossRefGoogle Scholar
  136. 136.
    D. Vander Jagt, L. Hunsaker, T. Vander Jagt, M. Gomez, D. Gonzales, L. Deck, R. Royer, Inactivation of glutathione reductase by 4-hydroxynonenal and other endogenous aldehydes. Biochem. Pharmacol. 53, 1133–1140 (1997)PubMedCrossRefGoogle Scholar
  137. 137.
    S. Hou, P. Nori, J. Fang, C. Vaca, Methylglyoxal induces hprt mutation and DNA adducts in human T lymphocytes in vitro. Environ. Mol. Mutagen. 26, 286–291 (1995)PubMedCrossRefGoogle Scholar
  138. 138.
    Y. Kang, L. Edwards, P.J. Thornalley, Effect of methylglyoxal on human leukaemia 60 cell growth: modification of DNA G1 growth arrest and induction of apoptosis. Leuk. Res. 20, 397–405 (1996)PubMedCrossRefGoogle Scholar
  139. 139.
    J. Du, H. Suzuki, F. Nagase, A. Akhand, X. Ma, T. Yokoyama, T. Miyata, I. Nakashima, Superoxide-mediated early oxidation and activation of ASK1 are important for initiating methylglyoxal-induced apoptosis process. Free Radic. Biol. Med. 31, 469–478 (2001)PubMedCrossRefGoogle Scholar
  140. 140.
    A. Okado, Y. Kawasaki, Y. Hasuike, M. Takahashi, T. Teshima, J. Fujii, N. Taniguchi, Induction of apoptotic cell death by methylglyoxal and 3-deoxyglucosone in macrophage-derived cell lines. Biochem. Biophys. Res. Commun. 225, 219–224 (1996)PubMedCrossRefGoogle Scholar
  141. 141.
    A. De Vriese, J. Van De Voorde, H. Blom, P. Vanhoutte, M. Verbeke, N. Lameire, The impaired renal vasodilator response attributed to endothelium-derived hyperpolarizing factor in streptozotocin-induced diabetic rats is restored by 5-methyltetrahydrofolate. Diabetologia 43, 1116–1125 (2000)PubMedCrossRefGoogle Scholar
  142. 142.
    H. Ding, M. Hashem, W. Wiehler, W. Lau, J. Martin, J. Reid, C. Triggle, Endothelial dysfunction in the streptozotocin-induced diabetic apoE deficient mouse. Br. J. Pharmacol. 146, 1110–1118 (2005)PubMedCrossRefGoogle Scholar
  143. 143.
    M. Pannirselvam, W. Wiehler, T. Anderson, C. Triggle, Enhanced vascular reactivity of small mesenteric arteries from diabetic mice is associated with enhanced oxidative stress and cyclooxygenase products. Br. J. Pharmacol. 144, 953–960 (2005)PubMedCrossRefGoogle Scholar
  144. 144.
    C. Sena, E. Nunes, T. Louro, T. Proença, R. Fernandes, M. Boarder, R. Seiça, Effects of alpha-lipoic acid on endothelial function in aged diabetic and high-fat fed rats. Br. J. Pharmacol. 153, 894–906 (2008)PubMedCrossRefGoogle Scholar
  145. 145.
    N. Rabbani, L. Godfrey, M. Xue, F. Shaheen, M. Geoffrion, R. Milne, P.J. Thornalley, Glycation of LDL by methylglyoxal increases arterial atherogenicity: a possible contributor to increased risk of cardiovascular disease in diabetes. Diabetes 60(7), 1973–1980 (2011)PubMedCrossRefGoogle Scholar
  146. 146.
    P. Thornalley, Dicarbonyl intermediates in the Maillard reaction. Ann. N. Y. Acad. Sci. 1043, 111–117 (2005)PubMedCrossRefGoogle Scholar
  147. 147.
    N. Rabbani, M. Chittari, C. Bodmer, D. Zehnder, A. Ceriello, P.J. Thornalley, Increased glycation and oxidative damage to apolipoprotein B100 of LDL cholesterol in patients with type 2 diabetes and effect of metformin. Diabetes 59, 1038–1045 (2010)PubMedCrossRefGoogle Scholar
  148. 148.
    P. Beisswenger, S.K. Howell, A. Touchette, S. Lal, B. Szwergold, Metformin reduces systemic methylglyoxal levels in type 2 diabetes. Diabetes 48, 198–202 (1999)PubMedCrossRefGoogle Scholar
  149. 149.
    X. Wang, K. Desai, T. Chang, L. Wu, Vascular methylglyoxal metabolism and the development of hypertension. J. Hypertens. 23, 1565–1573 (2005)PubMedCrossRefGoogle Scholar
  150. 150.
    X. Wang, K. Desai, J. Clausen, L. Wu, Increased methylglyoxal and advanced glycation end products in kidney from spontaneously hypertensive rats. Kidney Int. 66, 2315–2321 (2004)PubMedCrossRefGoogle Scholar
  151. 151.
    X. Wang, X. Jia, T. Chang, K. Desai, L. Wu, Attenuation of hypertension development by scavenging methylglyoxal in fructose-treated rats. J. Hypertens. 26, 765–772 (2008)PubMedCrossRefGoogle Scholar
  152. 152.
    S. Ogawa, K. Nakayama, M. Nakayama, T. Mori, M. Matsushima, M. Okamura, M. Senda, K. Nako, T. Miyata, S. Ito, Methylglyoxal is a predictor in type 2 diabetic patients of intima-media thickening and elevation of blood pressure. Hypertension 56, 471–476 (2010)PubMedCrossRefGoogle Scholar
  153. 153.
    M. Beeri, E. Moshier, J. Schmeidler, J. Godbold, J. Uribarri, S. Reddy, M. Sano, H. Grossman, W. Cai, H. Vlassara, J. Silverman, Serum concentration of an inflammatory glycotoxin, methylglyoxal, is associated with increased cognitive decline in elderly individuals. Mech. Ageing Dev. 132(11–12), 583–587 (2011)PubMedCrossRefGoogle Scholar
  154. 154.
    M. Fukunaga, S. Miyata, S. Higo, Y. Hamada, S. Ueyama, M. Kasuga, Methylglyoxal induces apoptosis through oxidative stress-mediated activation of p38 mitogen-activated protein kinase in rat Schwann cells. Ann. N. Y. Acad. Sci. 1043, 151–157 (2005)PubMedCrossRefGoogle Scholar
  155. 155.
    J. Berlanga, D. Cibrian, I. Guillén, F. Freyre, J. Alba, P. Lopez-Saura, N. Merino, A. Aldama, A. Quintela, M. Triana, J. Montequin, H. Ajamieh, D. Urquiza, N. Ahmed, P.J. Thornalley, Methylglyoxal administration induces diabetes-like microvascular changes and perturbs the healing process of cutaneous wounds. Clin. Sci. (Lond) 109(1), 83–95 (2005)CrossRefGoogle Scholar
  156. 156.
    X. Wang, W. Lau, Y. Yuan, Y. Wang, W. Yi, T. Christopher, B. Lopez, H. Liu, X. Ma, Methylglyoxal increases cardiomyocyte ischemia-reperfusion injury via glycative inhibition of thioredoxin activity. Am. J. Physiol. Endocrinol. Metab. 299(2), E207–E214 (2010)PubMedGoogle Scholar
  157. 157.
    L. Vona-Davis, D. Rose, Angiogenesis, adipokines and breast cancer. Cytokine Growth Factor Rev. 20, 193–201 (2009)PubMedCrossRefGoogle Scholar
  158. 158.
    A. Ozdemir, U. Hopfer, M. Rosca, X. Fan, V. Monnier, M. Weiss, Effects of advanced glycation end product modification on proximal tubule epithelial cell processing of albumin. Am. J. Nephrol. 28(1), 14–24 (2008)PubMedCrossRefGoogle Scholar
  159. 159.
    M. Coughlan, S. Patel, G. Jerums, S. Penfold, T. Nguyen, K. Sourris, S. Panagiotopoulos, P. Srivastava, M. Cooper, L. Burrell, R. Macisaac, J. Forbes, Advanced glycation urinary protein-bound biomarkers and severity of diabetic nephropathy in man. Am. J. Nephrol. 34(4), 347–355 (2011)PubMedCrossRefGoogle Scholar
  160. 160.
    S. Mauer, M. Steffes, E. Ellis, D. Sutherland, D. Brown, F. Goetz, Structural-functional relationships in diabetic nephropathy. J. Clin. Invest. 74, 1143–1155 (1984)PubMedCrossRefGoogle Scholar
  161. 161.
    A. Mostafa, E. Randell, S. Vasdev, V. Gill, Y. Han, V. Gadag, A. Raouf, H. El Said, Plasma protein advanced glycation end products, carboxymethyl cysteine, and carboxyethyl cysteine, are elevated and related to nephropathy in patients with diabetes. Mol. Cell. Biochem. 302(1–2), 35–42 (2007)PubMedCrossRefGoogle Scholar
  162. 162.
    B. Harcourt, K. Sourris, M. Coughlan, K. Walker, S. Dougherty, S. Andrikopoulos, A. Morley, V. Thallas-Bonke, V. Chand, S. Penfold, M. de Courten, M.C. Thomas, B.A. Kingwell, A. Bierhaus, M.E. Cooper, B. Courten, J.M. Forbes, Targeted reduction of advanced glycation improves renal function in obesity. Kidney Int. 80(2), 190–198 (2011)PubMedCrossRefGoogle Scholar
  163. 163.
    S. Tang, L. Chan, J. Leung, A. Cheng, M. Lin, H. Lan, K. Lai, Differential effects of advanced glycation end-products on renal tubular cell inflammation. Nephrology (Carlton). 16(4), 417–425 (2011)CrossRefGoogle Scholar
  164. 164.
    M. Rosca, T. Mustata, M. Kinter, A. Ozdemir, T. Kern, L. Szweda, M. Brownlee, V. Monnier, M. Weiss, Glycation of mitochondrial proteins from diabetic rat kidney is associated with excess superoxide formation. Am. J. Physiol. Renal. Physiol. 289, F420–F430 (2005)PubMedCrossRefGoogle Scholar
  165. 165.
    Y. Zhao, S. Banerjee, W. LeJeune, S. Choudhary, R. Tilton, NF-κB-inducing kinase increases renal tubule epithelial inflammation associated with diabetes. Exp. Diabetes Res. 2011, 192564 (2011)PubMedCrossRefGoogle Scholar
  166. 166.
    S. Nakatani, A. Kakehashi, E. Ishimura, S. Yamano, K. Mori, M. Wei, M. Inaba, H. Wanibuchi, Targeted proteomics of isolated glomeruli from the kidneys of diabetic rats: sorbin and SH3 domain containing 2 is a novel protein associated with diabetic nephropathy. Exp. Diabetes Res. 2011, 979354 (2011)PubMedCrossRefGoogle Scholar
  167. 167.
    A. Diez-Sampedro, O. Lenz, A. Fornoni, Podocytopathy in diabetes: a metabolic and endocrine disorder. Am. J. Kidney Dis. 58(4), 637–646 (2011)PubMedCrossRefGoogle Scholar
  168. 168.
    D. Fosmark, J. Berg, A. Jensen, L. Sandvik, E. Agardh, C. Agardh, K. Hanssen. Increased retinopathy occurrence in type 1 diabetes patients with increased serum levels of the advanced glycation endproduct hydroimidazolone. Acta Ophthalmol. 87(5), 498–500 (2009)PubMedCrossRefGoogle Scholar
  169. 169.
    Z. Wagner, P. Degrell, B. Lukáts, T. Niwa, G. Molnár, L. Markó, Z. Karádi, I. Wittmann, Accumulation of renin and imidazolone in peritubular capillary endothelial cells in insulin-resistant hypertensive rats. J. Nephrol. 24(5), 656–664 (2011)PubMedCrossRefGoogle Scholar
  170. 170.
    X. Wang, K. Desai, B. Juurlink, J. de Champlain, L. Wu, Gender-related differences in advanced glycation endproducts, oxidative stress markers and nitric oxide synthases in rats. Kidney Int. 69(2), 281–287 (2006)PubMedCrossRefGoogle Scholar
  171. 171.
    N. Reiniger, K. Lau, D. McCalla, B. Eby, B. Cheng, Y. Lu, W. Qu, N. Quadri, R. Ananthakrishnan, M. Furmansky, R. Rosario, F. Song, V. Rai, A. Weinberg, R. Friedman, R. Ramasamy, V. D’Agati, A. Schmidt, Deletion of the receptor for advanced Glycation end products reduces glomerulosclerosis and preserves renal function in the diabetic OVE26 mouse. Diabetes 59, 2043–2054 (2010)PubMedCrossRefGoogle Scholar
  172. 172.
    D. Fosmark, J. Berg, A. Jensen, L. Sandvik, E. Agardh, C. Agardh, K. Hanssen, Increased retinopathy occurrence in type 1 diabetes patients with increased serum levels of the advanced glycation endproduct hydroimidazolone. Acta Ophthalmol. 87(5), 498–500 (2009)PubMedCrossRefGoogle Scholar
  173. 173.
    O. Kim, J. Kim, C. Kim, N. Kim, J. Kim, KIOM-79 prevents methyglyoxal-induced retinal pericyte apoptosis in vitro and in vivo. J. Ethnopharmacol. 129(3), 285–292 (2010)PubMedCrossRefGoogle Scholar
  174. 174.
    J. Kim, J. Son, J. Lee, Y. Oh, S. Shinn, Methylglyoxal induces apoptosis mediated by reactive oxygen species in bovine retinal pericytes. J. Korean Med. Sci. 19(1), 95–100 (2004)PubMedCrossRefGoogle Scholar
  175. 175.
    R. Milne, S. Brownstein. Advanced glycation end products and diabetic retinopathy. Amino Acids (2011) [Epub Ahead of Print]Google Scholar
  176. 176.
    J. Kim, C. Kim, Y. Lee, K. Jo, S. Shin, J. Kim, Methylglyoxal induces hyperpermeability of the bloodretinal barrier via the loss of tight junction proteins and the activation of matrix metalloproteinases. Graefes Arch. Clin. Exp. Ophthalmol. 250(5), 691–697 (2012)PubMedCrossRefGoogle Scholar
  177. 177.
    O. Brouwers, P. Niessen, I. Ferreira, T. Miyata, P. Scheffer, T. Teerlink, P. Schrauwen, M. Brownlee, C. Stehouwer, C. Schalkwijk, Overexpression of glyoxalase-I reduces hyperglycemia-induced levels of advanced glycation endproducts and oxidative stress in diabetic rats. J. Biol. Chem. 286(2), 1374–1380 (2011)PubMedCrossRefGoogle Scholar
  178. 178.
    A. Sartori, H. Garay-Malpartida, M. Forni, R. Schumacher, F. Dutra, M. Sogayar, E. Bechara, Aminoacetone, a putative endogenous source of methylglyoxal, causes oxidative stress and death in insulin-producing RINm5f cells. Chem. Res. Toxicol. 21(9), 1841–1850 (2008)PubMedCrossRefGoogle Scholar
  179. 179.
    I. Nemet, L. Varga-Defterdarović, Z. Turk, Methylglyoxal in food and living organisms. Mol. Nutr. Food Res. 50(12), 1105–1117 (2006)PubMedCrossRefGoogle Scholar
  180. 180.
    J. Adolphe, M. Drew, Q. Huang, T. Silver, L. Weber, Postprandial impairment of flow-mediated dilation and elevated methylglyoxal after simple but not complex carbohydrate consumption in dogs. Nutr. Res. 32(4), 278–284 (2012)PubMedCrossRefGoogle Scholar
  181. 181.
    P.J. Beisswenger, S.K. Howell, R.M. O’Dell, M.E. Wood, A.D. Touchette, B.S. Szwergold, alpha-Dicarbonyls increase in the postprandial period and reflect the degree of hyperglycemia. Diabetes Care 24(4), 726–732 (2001)PubMedCrossRefGoogle Scholar
  182. 182.
    A.G. Miller, G. Tan, K.J. Binger, R.J. Pickering, M.C. Thomas, R.H. Nagaraj, M.E. Cooper, J.L. Wilkinson-Berka, Candesartan attenuates diabetic retinal vascular pathology by restoring glyoxalase-I function. Diabetes 59(12), 3208–3215 (2010)PubMedCrossRefGoogle Scholar
  183. 183.
    J. Xue, V. Rai, D. Singer, S. Chabierski, J. Xie, S. Reverdatto, D.S. Burz, A.M. Schmidt, R. Hoffmann, A. Shekhtman, Advanced glycation end product recognition by the receptor for AGEs. Structure 19(5), 722–732 (2011)PubMedCrossRefGoogle Scholar
  184. 184.
    R. Ramasamy, S. Yan, A. Schmidt, Receptor for AGE (RAGE): signaling mechanisms in the pathogenesis of diabetes and its complications. Ann. N. Y. Acad. Sci. 1243, 88–102 (2011)PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Paulo Matafome
    • 1
    • 2
    • 3
  • Cristina Sena
    • 1
  • Raquel Seiça
    • 1
  1. 1.Laboratory of PhysiologyInstitute of Biomedical Research on Light and Image (IBILI), Faculty of Medicine, University of CoimbraCoimbraPortugal
  2. 2.Center of OphthalmologyInstitute of Biomedical Research on Light and Image (IBILI), Faculty of Medicine, University of CoimbraCoimbraPortugal
  3. 3.Faculty of MedicinePole III of University of CoimbraCoimbraPortugal

Personalised recommendations