Decreased de novo Synthesis of Glomerular Proteoglycans in Diabetes: Biochemical and Autoradiographic Evidence

The experimental model of streptozotocin-induced diabetes in rats was utilized to determine the biosynthetic and biochemical alterations in the proteoglycans of the glomerular extracellular matrices (glomerular basement membrane and mesangial matrix) in diabetic nephropathy. Isolated kidneys from diabetic and control groups of animals were radiolabeled in an organ perfusion apparatus with [35S]sulfate of high specific activity (>1,200 Ci/mmol; 1 Ci =3.7× 1010Bq) and processed for electron microscopic autoradiography, and the proteoglycans of the glomerular extracellular matrices were characterized. The results indicate that [35S]sulfate incorporation into glomerular extracellular matrices of diabetic animals was 30-40% less than that of the control group; however, no differences in the biochemical properties of the de novo synthesized proteoglycans from either group were observed. The relevance of the decreased de novo synthesis of sulfated proteoglycans of glomerular extracellular matrices is discussed in terms of increased glomerular permeability to plasma proteins and reduction in the glomerular filtration rate.