Glomerulopathy in rats with streptozotocin diabetes. Accumulation of glomerular basement membrane analogous to human diabetic nephropathy

Abstract

Glomeruli from streptozotocin-diabetic and age-matched nondiabetic rats were quantitatively isolated by a differential sieving technique. The insoluble glomerular basement membranes were purified following sonic disruption in the presence of proteolytic inhibitors. The yield of glomeruli and of glomerular basement membrane relative to the amount of renal cortex and the body weight of the animals, as well as the calculated amount of basement membrane per glomerulus, were all significantly greater in diabetic rats when compared to non-diabetic controls. Glomerular basement membranes from normal and diabetic rats were solubilized by reduction and denaturation in the presence of SDS and subjected to agarose gel analysis. About 65% of both normal and diabetic basement membrane was solubilized by this procedure, and the elution profiles of non-diabetic and diabetic preparations were similar. These results suggest that rat renal basement membrane is qualitatively similar but quantitatively increased in streptozotocin-diabetes. Since glomerular enlargement and accumulation of basement membrane are characteristic of human diabetic nephropathy, the findings also suggest that the streptozotocin-diabetic rat is an appropriate animal model for studies relating to the pathogenesis of this complication of diabetes.