Alterations in glomerular permeability in streptozotocin-induced diabetic rats

The alteration in glomerular basement membrane permeability associated with microangiopathy in streptozotocin-induced diabetic rats was studied by determining the movement across the glomerular basement membrane of anionic ferritin probes injected into rats at different points in the development of the disease. Visualization of the concentration gradient of anionic ferritin and changes in ultrastructure was accomplished by electron microscopic examination of renal tissue prepared from both control and diabetic rats. In all control rats, the anionic ferritin did not leave the glomerular capillary lumen, nor were there any changes in the normal morphology of the glomerular capillary wall. In the diabetic animals, the concentration of anionic ferritin shifted from the capillary lumen in the abluminal direction. Distinct morphologic changes, such as widening of endothelial intercellular junctions, focal detachment of podocyte foot processes, and extensive thickening of the glomerular basement membrane, were noted in the diabetic rat, and these changes appear to correlate with the observed increase in permselectivity of anionic ferritin across the glomerular capillary wall.