[Molecular aspects of chronic hyperglycemia-induced tissue damage].

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.