Proteoglycans (PGs) are macromolecules widely distributed in animal tissues. They are important components of extracellular matrix and cell surface. PG degradation occurs mainly in lysosomes after endocytosis, by the action of proteases and endoglycosidases. These enzymes act upon the protein core and the glycosaminoglycan (GAG) side chains, respectively. Smaller fragments of GAGs are degraded to monosaccharides and sulfate by the sequential action of exoglycosidases and sulfatases in the lysosomes. Small amounts (around 10% of total) of partially degraded GAGs are excreted in urine. Changes in the urinary excretion of GAGs could be due to changes either in the systemic metabolism of these compounds, or in their renal processing. Our laboratory has shown that, in an experimental model of type I diabetes mellitus in rats, an important and early decrease in the urinary excretion of GAGs occurs. Diabetics also excreted reduced amounts of dextran sulfate, another sulfated polysaccharide. Higher amounts of dextran sulfate molecules of higher molecular weights were found in the liver and kidneys of diabetic rats 48 h after administration, suggesting intracellular location. These findings suggest that the excretion of sulfated polysaccharides does not depend only on the permeability of the glomerular basement membrane, but also may involve kidney cells. Hence, there may be differential renal processing mechanisms for albumin and sulfated polysaccharides, possibly involving lysosomal enzymes. Therefore, the objective of this study is to investigate the expression and the activity of lysosomal enzymes, as well as metalloproteases and inhibitors, in liver and kidney of diabetic rats in comparison to normal rats.
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