Glomerular basement membrane turnover in young, old, and streptozotocin-diabetic rats

Diabetic and senile glomerulosclerosis consists of thickening of the glomerular basement membranes (GBM) and augmentation of the mesangial matrix. The pathogenesis of these alterations is still controversial. Therefore, an in vivo study of the metabolism and the chemical composition of the GBM in streptozotocin-diabetic and old rats reported here was conducted: The turnover rate of the GBM, determined by the incorporation of labeled hydroxyproline, is prolonged in preparations from diabetic and aging rats. This can be explained by the decreased synthesis and delayed degradation of the GBM material found in both experimental groups. The biochemical analyses of the GBM revealed a higher content of hydroxylated amino acids, especially OH-lys, in the old and diabetic animals. The findings suggest that diabetic and senile glomerulosclerosis results from a prolonged turnover of the GBM and GBM-like material under the altered metabolic conditions investigated in this study.