GLOMERULAR BASEMENT-MEMBRANE - BIOSYNTHESIS AND CHEMICAL COMPOSITION IN STREPTOZOTOCIN DIABETIC RAT

To study the effect of streptozotocin induced diabetes on glomerular basement membrane (GBM) synthesis, an isolated rat glomerular preparation was developed and its metabolic properties defined. The chemical composition of normal rat GBM isolated from this preparation closely resembles human GBM. Incubation with [U-14C] lysine leads to prompt incorporation of label into GBM and the subsequent appearance of labeled hydroxylysine. A 1 h lag before detection of labeled hydroxylysine in GBM suggests a delay in the release of GBM precursors. Significantly lower counts appeared in the nondialyzable fraction of the medium than in insoluble GBM during pulse-chase experiments, and labeled hydroxylysine accounted for a lower portion of the total counts in the medium (0.85%) than in the GBM (1.98%). Isolated glomeruli were prepared from streptozotocin diabetic rats of 4-6 wk duration. After incubation with [U-14C] lysine recovery of label in diabetic GBM (88.98 .+-. 8.26 nmol/g GBM) did not differ from age matched controls (82.52 .+-. 8.26 nmol/g GBM.) In pulse-chase experiments recovery of label in hydroxylysine of diabetic GMB (0.473 .+-. 0.082 nmol/g GBM) did not differ from age matched controls (0.567 .+-. 0.065 nmol/g GBM). These findings indicate normal rates of GBM synthesis and hydroxylation of lysine residues in animals with streptozotocin diabetes. The chemical composition and morphology of the GBM was studied in rats with long term streptozotocin diabetes (14 mo.) to determine if the increase in hydroxylsine and glucosyl galactose and the decrease in lysine previously noted in the GBM in long-term human diabetes occurs in the rat. Except for minor changes in proline and arginine content, the chemical composition of diabetic rat GBM did not differ from age matched controls, while light microscopic studies of diabetic and control kidneys revealed equal degrees of mesangial and peripheral GBM changes.