medigraphic.com
ISSN 0016-3813 (Impreso)

2004, Número 4

<< Anterior Siguiente >>

Gac Med Mex 2004; 140 (4)


Aspectos moleculares del daño tisular inducido por la hiperglucemia crónica

Díaz-Flores M, Baiza-Gutman LA, Ibáñez-Hernández MA, Pascoe-Lira D, Guzmán-Greenfel AM, Kumate-Rodríguez J

Idioma: Español
Referencias bibliográficas: 71
Paginas: 437-448
Archivo PDF: 639.83 Kb.


RESUMEN

El propósito de este trabajo es dar a conocer las bases moleculares de la fisiopatología de la diabetes mellitus, con el fin de prevenir la enfermedad o mejorar el tratamiento. La diabetes mellitus es una enfermedad compleja, donde la hiperglucemia crónica provoca complicaciones en distintos órganos. En esta condición aumentan las especies reactivas de oxígeno como resultado de su autooxidacción, por lo que su metabolismo propicia la acumulación de metabolitos como la fructosa, el sorbitol y las triosas fosfato. Éstos últimos generan α-oxoaldehídos reactivos con alta capacidad de unirse a proteínas y generar estrés oxidativo. Además, hay aumento de la síntesis de diacilgliceroles a partir de las triosas fosfato, las cuales activan a la proteína cinasa C. Por otra parte, la alteración de la proporción normal entre los nucleótidos de niacinamida reducidos con respecto a los oxidados conduce a una baja eficiencia de los sistemas antioxidantes. Finalmente, estas desregulaciones metabólicas causan alteración en la transducción de la señal, en la expresión anormal de genes, además de daño tisular, lo que propicia complicaciones en los pacientes con diabetes.


REFERENCIAS (EN ESTE ARTÍCULO)

  1. Secretaría de Salud. Encuesta Nacional de Enfermedades Crónicas. México: Secretaría de Salud; 2000.

  2. Kahan R. Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care 1997;20:1183-1193.

  3. Lebovitz HE. Type 2 diabetes: an overview. Clin Chem 1999;45(8 pt 2):1339-1345.

  4. Browniee M. Biochemistry and molecular cell biology of diabetic complications. Nature 2001;414(6865):813-820.

  5. Thornally PJ, Jahan I, Ng R. Suppression of the accumulation of triosaphosphates and increased formation of methylglyoxal in human red blood celis during hyperglycaemia by thiamine in vitro, J Biochem 2001;129:543-549.

  6. Méndez JD. Productos finales de glicación avanzada y complicaciones crónicas de la diabetes mellitus. Gac Med Mex 2003;139:49-54.

  7. Uirich P, Cerami A. Protein glycation, diabetes, and aging. Recent Progr Horm Res 2001;56:1-21.

  8. Thornalley PJ. Glycation in diabetic neuropathy: characteristics, consequences, causes and therapeutic options. Int Rev Neurobiol 2002;50:37-57.

  9. Gabbay KH. Hyperglycaemia, polyol metabolism, and complications of diabetes mellitus. Annu Rev Med 1975;26:521-536.

  10. Marshall S, Bacote V, Traxinger RR. Discovery of a metabolic pathway mediating glucose induced desensitization of the glucose transport system. Role of hexosamine biosynthesis in the induction of insulin resistance. J Biol Chem 1991;1266(8):4706-4712.

  11. Koya D, King GL. Protein kinase C activation and the development of diabetic complications. Diabetes 1998;47(6):859-866.

  12. Baynes JW, Thorpe SR. Role of oxidative stress in diabetic complications: a new perspectiva on an old paradigm. Diabetes 1999;48(1):1-9.

  13. Maritim AC, Sanders RA, Watkins JB 3rd. Diabetes, oxidative stress, and antioxidants: a review. J Biochem Mol Toxicol 2003;17(1):24-38.

  14. Turner R. The U.K. Prospective Diabetes Study. A review. Diabetes Care 1998;21(3):C35-C38.

  15. Clark CJ, Lee D. Prevention and treatment of the complications of diabetes mellitus. N Engl J Med 1995;332:1210-1217.

  16. Fore W. Noninsulin-dependent diabetes mellitus. The prevention of complications. Med Clin North Am 1995;79(2):287-298.

  17. American Diabetes Association. Consensus Statement: Role of cardiovascular risk factors in prevention and treatment of macro-vascular disease in diabetes. Diabetes Care 1993;16(Suppl 2):72-78.

  18. Cai L, Kang YJ. Oxidative stress and diabetic cardiomyopthy: a brief review. Cardiovasc Toxicol 2001;1(3):181-193.

  19. De Vriese AS, Verbeuren TJ, Van de Voorde J, Lameire NH, Vanhoutte PM. Endotelial dysfunction in diabetes. Br J Pharmacol 2000;1130(5):963-974.

  20. Morauski CJ, Skinner SL, Stubbs AJ. The renin-angiotensin system influences ocular endothelial cell proliferation in diabetes: transgenic and interventional studies. Am J Pathol 2003;162(1):151-160.

  21. Stitt A, Gardiner TA, Alderson NL, Canning P, Frizzell N, Duffy N, Boyle C, Januszewski AS, Chachich M, Baynes JW, Thorpe SR, Anderson NL. The AGE inhibitor pyridoxamine inhibits development of retinopathy in experimental diabetes. Diabetes 2002;51(9):2826-2832.

  22. Zorina SG, Khatri JJ. Matrix metalloproteinases in vascular remodeling and atherogenesis. The good, the bad and the ugly. Circ Res 2002;90:251-262.

  23. Monnier VM, Sell DR, Odetti P. Maillard reaction and oxidative stress are interrelated stochastic mechanisms of aging. Poli G, Albano E, Dianzani UM, editores. Free radicals: from basic science to medicine. Basel, Suiza: Birkháuser Veriag;1993.

  24. Niwa T. 3-deoxygiucosone: metabolism, analysis, biological activity, and clinical implication. J Chromatogr B Biomed Sci Appl 1999;731(1):23-26. 25. Best L, Thornally PJ. Trioses and related substances: tools for the study of pancreatic beta cell function. Biochem Pharmacol 1999;57(6):583-588.

  25. Wells-Knecht KJ, Lyons TJ, McCance DR, Thorpe SR, Feather MS, Baynes JW. 3-deoxyfructose concentrations are increased in human plasma and urine in diabetes. Diabetes 1994;43(9):1152-1156.

  26. Yamada H, Miyata S, lgaki N, Yatabe H, Miyauchi Y, Ohara T, Sakai M, Soda H, Oimomi M, Kasuga M. Increase in 3-deoxyglucosone leveLs in diabetic rat plasma. Specific in vivo determination of intermediate and advanced Maillard reaction. J Biol Chem 1994;69(32):20275-20280.

  27. Degenhardt TP, Thorpe SR, Baynes JW. Chemical modification of proteins by methygiyoxal. Cell Mol Biol 1998;44(7):1139-1145.

  28. Thornalley P. Cell activation by glycated proteins. AGE receptors, receptor recognition factors and functional classification of AGES. Cell Mol Biol 1998;44:1013-1023.

  29. Mohamed AK, Bierhaus A, Schiekofer S, Ziegier R, Nawroth PP. The role of oxidative stress and NF-kappaB activation in late diabetic complications. Biofactors 1999;10(2-3):157-167.

  30. Hofmann MA, Schiekofer S, Iserman B, Kanitz M, Henkeis M, Joswing M, Treuch A, Marcos M, Weiss T, Borcea V, Abdel Khalek AK, Amiral J, Tritschier H, Ritz E, Wahi P, Ziegler R, Bierhaus A, Nawroth PP. Peripheral blood mononuclear cells isolated from patients with diabetic nephropathy show increased activation of the oxidative-stress sensitive transcription factor NFkappa B. Diabetologia 1999:42(2):222-232.

  31. Giardino I, Edeistein D, Browlee M. BCI-2 expression or antioxidants prevent hyperglycemia-induced formation of intracellular advanced glycation end products in bovine endothelial cells. J Clin Invest 1996;97(6):1422-1428.

  32. Hodgkinson AD, Sondergaard KL, Yang B, Cross DF, Miiiward BA, Demaine AG. Aldose redactase expression is induced by hyperglycemia in diabetic nephropathy. Kidney Int 2001;60(1):211-218.

  33. Meister A. Biochemistry of glutathione. En: De D, Greenberg, editores. Metabolism of sulfur compounds. New York: Academic Press;1975. pp. 101-188.

  34. Diplock AT. Antioxidants and free radical scavengers. En: Rice-Evans CA, Burdon RH. Elsevier Science LLM , editores. Free radical damage and its control. Amsterdam, Holanda: Elsevier Science BV 1994;99:113-130.

  35. Trueblood N, Ramasamy R. Aldose reductase inhibition improves altered glucose metabolism of isolated diabetic rat hearts. Am J Physiol 1998;275(1 Pt 2):H75-H83.

  36. Gabbay KH. Hyperglycemia, polyol metabolism, and complicantions of diabetes mellitus. N Engl J Med 1975;521-536.

  37. Fukase S, Sato S, Morl K, Secchi EF, Kador PF. Polyol pathway and NADPHdependent reductases in dog leukocytes. J Diabetes Complications 1996;10(6):304-313.

  38. Knecht E, Roche E. The reduction-oxidation status may influence the degradation of glyceraldehyde-3-phosphate dehydrogenase. FEBS Lett 1986;206(2):339-342.

  39. Morgan PE, Dean RT, Davis MJ. Inhibition of glyceraldehyde-3-phosphate dehydrogenase by peptide and protein peroxides generated by singlet oxygen attack. Eur J Biochem 2002;269:1916-1925.

  40. Alexander MC, Lomato M, Nasrin N, Ramaika C. Insulin stimulates giyceraldehyde-3-phosphate dehydrogenase gene expression through cis-acting DNA sequences. Proc Natl Acad Sci USA 1988:185:5092-5096.

  41. Novotny MV, Yancey MF, Yanuy MF, Stuart R, Weisler D, Peterson RG. lnhibition of glycolytic enzymes by endogenous aldehydes: a possible relation to diabetic neuropathies. Biochim Biophys Acta 1994;1226(2):145-150.

  42. Beisswenger PJ, Howeil SK, Smith K, Szwergofd BS. Glyceraldehyde-3-phosphate dehydrogenase activity as an independent modifier of methylglyoxal levels in diabetes. Biochim Biophys Acta 2003;1637(1):98-106.

  43. Szwergold BS, Kappier F, Brown TR. Identification of fructose 3- phosphate in the lens of diabetic rats. Science 1990;247(4941):451-454.

  44. Kusunoki H, Miyata S, Ohara T, Liu BF, Uriuhara A, Kojima H, Suzuki K, Miyazaki H, Yamashita Y, lnaba K, Kasuga M. Relation between serum 3-deoxyglucosone and development of diabetic microangiopathy. Diabetes Care 2003;26(6):1889-1894.

  45. Burg M, Kador PF. Sorbitol, osmoregulation, and the complications of diabetes, J Clin lnvest 1988;81(3):635-640.

  46. Lee AY, Chung SS. Contributions of polyol pathway to oxidative stress in diabetic cataract. FASEB J 1999;13(1)-23-30.

  47. Naruse K, Nakamura J, Hamada Y, Nakayama M, Chaya S, Komori T, Kato K, Kasuya Y, Miwa K, Hotta N. Aldose reductase inhibition prevents glucoseinduced apoptosis in cultured bovine retinal microvascular pericytes. Exp Eye Res 2000;71(3):309-315.

  48. Tilton RG, Chang K, Nyengaard JR, Van den Enden M, Ido Y, Williamson JR. lnhibition of sorbitol dehydrogenase. Effects on vascular and neural dysfunction in streptozocininduced diabetic rats. Diabetes 1995;44(2):234-242.

  49. Koim-Litty V, Sauer U, Nerfich A, Lehmann R, Schieicher ED. High glucoseinduced transforming growth factor beta 1 production is mediated by the hexosamine pathway in porcine glomerular mesangial cells. J Clin Invest 1998; 101(1):160-169.

  50. Du XL, Edeistein D, Rossetti L, Fantus IG, Goldeberg H, Ziyadeh F, Wu J, Brownlee M. Hyperglycemia-induced mitochondrial superoxide overproduction activases the hexosamine pathway and induces plasminogen activator inhibitor-1 expression by increasing Spl giycosilation. Proc Natl Acad Sci USA 2001; 97(22):12222-12226.

  51. Hawkins M, Barzilai N, Liu R, Hu M, Chen W, Rossetti L. Role of the glucosamine pathway in fat-induced insulin resistance. J Clin Invest 1997;99(9):2173~2182.

  52. McClain DA, Crook ED. Hexosamines and insulin resistance. Diabetes 1996;45(8):1003-1009.

  53. Baron AD, Zhu JS, Garvey WT, et al. Glucosamine induces insulin resistance in vivo by affecting GLUT 4 translocation in skeietal muscie. J Clin lnvest 1995;96:2792-2801.

  54. Hebert LF, Danieis MC, Zhou J, Crook ED, Turner RL, Simmons ST, Neidigh JL, ZHU JS, Baron AD, McCiain DA. Overexpression of glutamine: fructose-6-phosphate amidotransferase in transgenic mice leads to insulin resistance. J Clin lnvest 1996;98:930-936.

  55. Liu K, Paterson AJ, Chin E, Kudiow JE. Glucose stiniulates protein modification by O-Iinked GicNAc in pancreatic beta celis: linkage of O-Iinked GlcNAc to beta cell death. Proc Natl Acad Sci USA 2000;97(6):2820-2825.

  56. Welis L, Vosseller K, Hart GW. Giycosylation of nucleocytopiasmic proteins: signal transduction and 0-GIcNAc. Science 2001;291(5512):2376-2378.

  57. Patti ME, Virkamaki A, Landoker EJ, Kahn CR, Yki-Jarvinen H. Activation of the hexosamine pathway by glucosamine in vivo induces insulin resístanse of eariy postreceptor insulin signaling events in skeletal muscie. Diabetes 1999;48(8):1562-1571.

  58. Yuan SY, Ustinova EE, Wu MH, Tinsiey JH, Xu W. Korompai FL, Taulman AC. Protein kinase C activation contributes to microvascular barrier dysfunction in the heart at early stages of diabetes. Circ Res 2000;87(5):412-417.

  59. Chibber R, Ben-Mahmud BM, Kohner EM, et al. Protein kinase C beta 2-dependent phosphorylation of core 2 GlcNAc-T promotes leukocyte-endothelial cell adhesion: a mechanism underlying capillary occiusion in diabetic retinopathy. Diabetes 2003;52(6):1519-1527.

  60. Wolf BA, Williamson JR, Easom RA, Chang K, Sherman WR, Turk J. Diacylglycerol accumulation and microvascular abnormalities induced by elevated glucose levels. J Clin Invest 1991;87:31-38.

  61. Godbout JP, Pesavento J, Hartman ME, Manson SR, Freund GG. Methylglyoxal enhances cisplatin-induced cytotoxicity by activating protein kinase C delta. J Biol Chem 2002;277(4):2554-2561.

  62. Filippis A, Ciark S, Proietto J. Increased flux through the hexosamine biosynthesis pathway inhibits glucose transport acutely by activation of protein kinase C. Biochem J 1997;1324(Pt 3):981-985.

  63. Scivittaro V, Ganz MB, Weiss MF. AGEs induce oxidative stress and activate protein kinase C-beta(11) in neonatal mesangial cells. Am J Physiol Renal Physiol 2000; 278(4):F676-F683.

  64. Lindschau C, Quass P, Halier H, et al. Glucose-induced TGF-beta 1 and TGFbeta receptor expression in vascular smooth muscle cells is mediated by protein kinase Caipha. Hypertension 2003;42(3):335-341.

  65. Park JY, Takahara N, Gabriele A, Chou E, Naruse K, Sazuma K, Yamauchi T, Ha SW, Meier M, Rhodes CJ, King GL. Induction of endothelin-1 expression by glucose: an effect of protein kinase C activation. Diabetes 2000;49(7):1239-1248.

  66. Gugiiucci A, Menini T. The poiyamines spermine and spermidine protect proteins from structural and functional damage by AGE precursors; a new role for old molecules? Life Sci 2003;72(23):2603-2616.

  67. Jaspan JB, Towie VL, Maselli R, Herold K. Clinical studies with an aldose reductase inhibitor in the automatic and somatic neuropathies of diabetes. Metabolism 1986-135:83-92.

  68. Foppiano M, Lombardo G. Worldwide pharmacovigilance systems and tolrestat withdrawal. Lancet 1997;349:399-400.

  69. Davids J, editor: Pfizer suspends zenarestat. Scrip 2000;2584:24 (October 18 th).

  70. Nigishi H, Toyota T, Sakamoto N. Clinical efficacy of fidarestat, a novel aldose reductase inhibitor, for diabetic peripheral neuropathy. Diabetes Care 2001;24: 1776-1782.

  71. Wendt TM, Tanji N, Guo J, Kislinger TR, Qu W, Lu Y, Bucciarefli LG, Rong LL, Mosher B, Markowitz GS, Stein G, Bierhaus A, Liliensiek B, Arnold B, Naeroth PP, Stern DM, D’Agati VD, Schmidt AM. RAGE drives the development of glomerulosclerosis and implicates podocyte activation in the pathogenesis of diabetic nephropathy. Am J Pathol 2003;162(4):1123-1137.




2020     |     www.medigraphic.com