Glicación de proteínas como elemento esencial en las complicaciones crónicas de la diabetes mellitus

Richard Sera Blanco, Moraima García Díaz, Ramón Moreira Cabrera

Texto completo:

PDF HTML

Resumen

La hiperglicemia es considerada en la actualidad como un factor causal clave en el desarrollo de las complicaciones vasculares diabéticas, pudiendo producir sus efectos nocivos por múltiples vías. Esto ha sido confirmado por el estudio Diabetes Control and Complication Trial de 1993, para la microangiopatía en el caso de la diabetes tipo 1 y corroborado por el United Kingdom Prospective Diabetes Study publicado a fines de 1998 para el caso de la diabetes tipo 2. En esta revisión se resumen las evidencias actuales en apoyo del rol de la hiperglicemia en las complicaciones vasculares del paciente con diabetes mellitus. Se profundiza en uno de los mecanismos bioquímicos protagónicos en esta enfermedad: la glicación o glicosilación noenzimática y se hace énfasis en la acción deletérea directa de la glucosa y otros monosacáridos sobre las proteínas así como la evidencia obtenida en estudios en animales y en ensayos clínicos de fase III, en apoyo de que la aminoguanidina, un inhibidor de la glicación, que retarda la aparición y modifica el curso de estas complicaciones. Se describe como los AGEs se unen a los receptores correspondientes y desencadenan una serie de mecanismos que conllevan al trastorno de la coagulación, a la aterogénesis y a los cambios de la membrana basal glomerular, produciéndose como consecuencia la proteinuria, la esclerosis y la expansión mesangial características de la etapa final de la enfermedad renal diabética. Un estricto control de las cifras de glicemia en la actualidad y el uso de fármacos antagonistas de la formación de los compuestos AGEs permitirán una mejor profilaxis de las complicaciones vasculares en esta enfermedad.

 

Palabras clave

Diabetes mellitus; complicaciones

Referencias

Stern M. Diabetes and cardiovascular disease: the "common soil" hypothesis. Diabetes 1995; 44: 369-74.

Bodansky HJ, Cudworth AG, Drury PL, Kohner EM. Risk factors associated with severe proliferative retinopathy in insulin-dependent diabetes mellitus. Diabetes Care 1982; 5: 97-100.

Lorenzi M. Glucose toxicity in the vascular complications of diabetes: the cellular perspective. Diabetes/Metab Rey 1992; 8: 85-103.

The Diabetes Control and Complications Trial Data Group. The effect of intensive diabetes management on macrovascular events and risk factors in the Diabetes Control and Complications Trial. Am J Cardiol 1995; 75: 894-903.

The Diabetes Control and Complications Trial Data Group. The relationship of glycemic exposure (HbA1c) to the risk of development and progression of retinopathy in the Diabetes Control and Complications Trial. Diabetes 1995; 44: 968-83.

The United Kingdom Prospective Diabetes Study Data Group. Intensive blood-glucose control with sulphonylureas or insulin compared with convencional treatment and risk of compli-cations in patients with type 2 diabetes (UKPDS 33). Lancet. 1998; 352: 837-53.

Gabbay K. The sorbitol pathway and the complications of diabetes. N Engl J Med 1973; 288: 831-6.

Boel E, Selmer J, Flodgaard H, Jensen T. Diabetic late complications: will aldose reductase inhibitors or inhibitors of advanced glycosylation endproduct formation hold promise? J Diabetes Compl 1995; 9: 104-29.

Maillard LC. Condensation des acides aminés sur les sucres; formation de melanoidines par voie méthodique. CR Acad Sci Paris 1912; 154: 66-8.

Ziyadeh F. Mediators of hyperglycemia and the pathogenesis of matrix accumulation in diabetic renal disease. Miner Electrolyte Metab 1995; 21: 292-302.

Baynes J, Thorpe S. Role of oxidative stress in diabetic complications: a new perspective on an old paradigm. Diabetes 1999; 48:1-9.

Giugliano D, Ceriello A, Paolisso G. Diabetes mellitus, hypertension, and cardiovascular disease: which role for oxidative stress?. Metabolism 1995; 44: 363-8.

Lopes-Virella M, Virella G. Cytokines, modified lipo-proteins, and arteriosclerosis in diabetes. Diabetes 1996; 45 (Suppl 3): S40-4.

Monnier V. Toward a Maillard reaction theory of aging. En: Baynes JW, Monnier VM, ed. Proceedings of the NIH Conference on the Maillard Reaction in Aging, Diabetes and Nutrition. New York: Liss; 1989.p. 1-22.

Stevens VJ, Vlassara H, Abati A, Cerami A. Nonenzy-matic glycosylation of hemoglobin. J Biol Chem 1977; 252: 2988-3002.

Armbruster DA. Fructosamine: structure, analysis and clinical usefulness. Clin Chem 1987; 33: 2157-63.

Menini T, Gugliucci A, Sodahlon YK, Stahl AJC, Blickle JF, Brogard JM. Glycated immunoglobulin M in diabetic patients. Ann Biol Clin 1993; 51: 887-91.

Njoroge FG, Monnier VM. The chemistry of the Maillard reaction under physiological conditions: a review. Prog Clin Biol Res 1989; 304: 85-91.

Hunt JV, Smith CT, Wolfe SP. Autoxidative glycosylation and possible involvement of peroxides and free radicals in LDL modification by glucose. Diabetes 1990; 39: 1420-4.

Giardino I, Edelstein D, Brownlee M. Nonenzymatic glycosylation in vitro and in bovine endothelial cells alters basic fibroblast growth factor activity. J Clin Invest 1994; 94:110-7.

Giardino I, Edelstein D, Brownlee M. BCL-2 expression or antioxidants prevent hyperglycemia-induced formation of intracellular advanced glycation end products in bovine endothelial cells. J Clin Invest 1996; 97: 1422-8.

Fujii E, Iwase H, Ishii-Karakasa I, Yajima Y, Hotta K. The presence of 2-keto-3- deoxygluconic acid and oxoaldehyde dehydrogenase activity in human erythrocytes. Biochem Biophys Res Commun 1995; 210(3): 852-7.

Monnier VM, Kohn RR, Cerami A. Accelerated age-related browning of human collagen in diabetes melitus. P Natl Acad Sci USA 1984; 81: 583-9.

Brownlee M, Pongor S, Cerami A. Covalent attachment of soluble proteins by nonenzymatically glycosylated collagen: role in the in situ formation of immune complexes. J Exp Med 1983; 158: 1739-44.

Bailey A, Sims TJ, Avery NC, Miles CA. Chemistry of collagen cross-links: glucosemediated covalent cross-linking of type-IV collagen in lens capsules. Biochem J 1993; 296: 489-97.

Haitoglou CS, Tsilibary EC, Brownlee M, Charonis AS. Altered cellular interactions between endothelial cells and non enzymatic glycosylated laminin/type IV collagen. J Biol Chem 1992; 267: 12404-7.

Lloyd-Jones D, Bloch K. The vascular biology of nitric oxide and its role in atherogenesis. Ann Rev Med 1996; 47: 365-75.

Darley-Usmar V, Wiseman H, Halliweli B. Nitric oxide and oxygen radicals: a question of balance. FEBS Letters 1995; 369: 131-5.

Thornalley P. Cell activation by glycated proteins: AGE receptors, receptor recognition factors and functional classification of AGEs. Cell Mol Biol 1998; 44: 1013-23.

Yan SD, Schmidt AM, Anderson GM, Zhang J, Brett J, Zou YS, et al. Enhanced cellular oxidant stress by the interaction of advanced glycation end products. with their receptors/binding proteins. J Biol Chem 1994; 269: 9889-97.

Wautier J, Zoukourian C, Chappey O, Wautier M, Guillausseau P, Cao R et al. Receptormediated endothelial cell dysfunction in diabetic vasculopathy. Soluble receptor for advanced glycation end products blocks hyperpermeability in diabetic rats. J Clin Invest 1996; 97: 238-43.

Bierhaus A, Illmer T, Kasper M, Luther T, Quehenberger P, Tritschler H, et al. Advanced glycation end product (AGE) mediated induction of tissue factor in cultured endothelial cells is dependent on RAGE. Circulation 1997; 96: 2262-71.

Skolnik EY, Yang Z, Makita Z, Radoff S, Kirstein M, Vlassara H. Human and rat mesangial cell receptors for glucose-modified proteins: potential role in kidney tissue remodeling and diabetic nephropathy. J Exp Med 1991; 174: 931-9.

Giardino I, Fard AK, Hatchell DL, Brownlee M. Amino-guanidine inhibits reactive oxygen species formation, lipid peroxidation, and oxidant-induced apoptosis. Diabetes 1998; 47(7): 1114-20.

Bucala R, Model P, Cerami A. Modification of DNA by reducing sugars: a possible mechanism for nucleic acid aging and age-related dysfunction in gene expression. Proc Natl Acad Sci USA 1984; 81: 105-9.

Bucala R, Model P, Russel M, Cerami A. Modification of DNA by glueose-6-phosphate induces DNA rearrangements in an E. coli plasmid. Proc Natl Acad Sel USA 1985; 82: 8439-42.

Kaneto H, Fujii J, Myint T, Miyazawa N, Islam KN, Kawasaki Y, Suzuki K et al. Reducing sugars trigger oxidative modification and apoptosis in pancreatic beta-cells by provoking oxidative stress through the glycation reaction. Biochem J 1996; 320(3): 855-63.

Makita Z, Vlassara H, Rayfield E, Cartwright K, Friedman E, Rodby R, et al. Hemoglobin- AGE: a circulating marker for advanced glycosylation. Science 1992; 258: 651-3.

McPherson J, Shilton B, Walton D. Role of fructose in glycation and cross-linking of proteins. Biochemistry 1988; 27: 1901-7.

Takagi Y, Kashiwagi A, Tanaka Y, Asahina T, Kikkawa RYS. Significance of fructoseinduced protein oxidation and formation of advanced glycation end product. J Diabetes Complications 1995; 9: 87-91.

Makita Z, Bucala R, Rayfield EJ, Friedman EA, Kaufman AM, Korbet SM, et al. Reactive glycosyation end products in diabetic uraemia and treatment of renal failure. Lancet. 1994; 343: 1519-22.

Bucala R, Vlassara H. Advanced glycosylation end products in diabetic renal and vascular disease. A J Kidney Dis 1995; 26: 875-88.

Fuh H, Yang D, Striker L, Striker G, Vlassara H. In vivo AGE peptide injection induces kidney enlargement and glomerular hypertrophy in rabbits: prevention by aminoguanidine. Diabetes. 1992; 41: 9A.

Gugliucci A, Bendayan M. Renal fate of advanced glycation products: evidence for reabsorption and catabolism of advanced glycation peptides by renal proximal tubular cells. Diabetologia. 1996; 39: 149-60.

Sell DR, Monnier VM. End-stage renal disease and diabetes catalyze the formation of a pentose-derived crosslink from aging human collagen. J Clin Invest 1990; 85(2): 380-4.

Bucala R, Cerami A. Phospholipids react with glucose to initiate advanced glycosylation and fatty acid oxidation: inhibition of lipid advanced glycosylation and oxydation by aminoguanidine. Diabetes. 1992;41(23A):91.

Gugliucci A, Menini T, Stahl AJC, Brogard JM. Advanced glycation of immunoglobulin G abd albumin in type 2 diabetie patients. Clin Chim Acta 2000 (En prensa).

Bierman E. Atherogenesis in diabetes. Atheroscler Thromb 1992; 12: 647-56.

Berliner J, Heinecke J. The role of oxidized lipoproteins in atherogenesis. Free Radic Biol Med 1996; 20: 707-27.

Lyons T. Lipoprotein glycation and its metabolic consequences. Diabetes 1992; 41: 67-73.

Kobayashi K, Watanabe J, Umeda F, Nawata H. Glycation accelerates the oxidation of low density lipoprotein by copper ions. Endocr J 1995; 42: 461-5.

Gugliucci A, Menini T, Stahl AJC. Susceptibility to copper-enhanced autoxidation of VLDL +LDL fractions from diabetic patients. Biochem Mol Biol Int 1994; 32: 139-47.

Gugliucci A, Dumont S, Siffert JC, Stahl AJC. Comparative interaction of glycated and oxidized low density lipoproteins with human monocyte-derived macrophages. Int J Immunopathol Pharmacol 1993; 6: 51-7.

Calvo C, Ulloa N, Del Pozo R, Verdugo C. Decreased activation of lecithin: cholesterol acyltransferase by glycated apolipoprotein A-I. Eur J Clin Chem Clin Biochem 1993; 31: 217-20.

Brownlee M, Vlassara H, Kooney T, Ulrich P, Cerami A. Aminoguanidine prevents diabetesinduced arterial wall protein cross-linking. Science. 1986; 232: 1629-32.

Huijberts MSP, Wolffenbuttel BHR, Crijns FRL, Nieuwenhuijsen Kruseman AC, Bemelmans MHA, Struijker Boudier HAJ. Aminoguanidine reduces regional albumin clearance but not urinary albumin excretion in streptozotocin-diabetic rats. Diabetologia. 1994; 37: 10-4.

Hammes HP, Brownlee M, Edelstein D, Saleck M, Federlin MK. Aminoguanidine inhibits the development of accelerated diabetic retinopathy in the spontaneous hypertensive rat. Diabetologia. 1994; 37: 32-5.

Enlaces refback

  • No hay ningún enlace refback.


Copyright (c) 2020 Richard Sera Blanco, Moraima García Díaz, Ramón Moreira Cabrera

Licencia de Creative Commons
Este obra está bajo una licencia de Creative Commons Reconocimiento-NoComercial 4.0 Internacional.