Fig. 8.

Schematic diagram for accumulation of PRPs and up-regulation of proteins. The proposed model shows that AGE modification and impairment in proteasomal activity results in accumulation of protease resistant aggregates. AGE modification causes loss of functional activity of enzymes, which is compensated by increased gene expression. Both the inability of proteasome to remove protease resistant aggregates and decreased enzyme activity may cause up-regulation of proteins in the diabetic condition.