[Molecular aspects of chronic hyperglycemia-induced tissue damage]. / Aspectos moleculares del daño tisular inducido por la hiperglucemia crónica.

The knowledge of the molecular basis of diabetes mellitus physiopathology will allow improvements in treatment or prevention of the disease. Diabetes mellitus is a complex disease in which hyperglycemia leads to complications in several organs. In this condition, there is increase in reactive oxygen species (ROS) as a result of glucose autooxidation; its metabolism produces accumulation of metabolites such as fructose, sorbitol, and triose phosphate. The latter generates a oxoaldehydes with high capacity to produce protein glycation and oxidative stress. Moreover, there is an increase in synthesis of diacylglycerol from triosephosphate, which activates protein kinase C. On the other hand, alteration of normal ratio between reduced and oxidized niacinamide nucleotides leads to low efficiency of antioxidative systems. Finally, this metabolic dysregulation causes altered signal transduction, abnormal gene expression, and tissue damage, resulting in development of diabetic complications.

Aspectos moleculares del daño tisular inducido por la hiperglucemia crónica / Molecular Aspects of Chronic Hyperglycemia-Induced Tissue Damage

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 pro teína 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.

The knowledge of the molecular basis of diabetes mellitus physiopathology will allow improvements in treatment or prevention of the disease. Diabetes mellitus is a complex disease in which hyperglycemia leads to complications in several organs. In this condition, there is increase in reactive oxygen species (ROS) as a result of glucose autooxidation; its metabolism produces accumulation of metabolites such as fructose, sorbitol, and triose phosphate. The latter generates α oxoaldehydes with high capacity to produce protein glycation and oxidative stress. Moreover, there is an increase in synthesis of diacylglycerol from triose phosphate, which activates protein kinase C. On the other hand, alteration of normal ratio between reduced and oxidized niacinamide nucleotides leads to low efficiency of antioxidative systems. Finally, this metabolic dysregulation causes altered signal transduction, abnormal gene expression, and tissue damage, resulting in development of diabetic complications.