Decreased proteinase activity in isolated glomeruli of streptozotocin diabetic rats

The important initiating process of diabetic nephropathy is the glomerular accumulation of proteins which has been proposed to be due to a synergistic interaction of the disturbed intrarenal hemodynamic and the altered chemical composition of glomerular components. This study was performed to investigate whether there might be a reduced activity of glomerular proteinases in streptozotocin diabetic rats. Three weeks after the induction of diabetes by means of streptozotocin, we found a decreased proteinase activity in ultrasonically destroyed isolated glomeruli obtained by a differential sieving technique in comparison to nondiabetic controls. This held true at acidic (16.59 +/- 1.56 vs. 22.19 +/- 1.94 U/min/mg protein) as well as at neutral pH (7.82 +/- 0.55 vs. 10.67 +/- 0.81 U/min/mg protein) and could be confirmed when proteinase activity was related to the single glomerulus or DNA instead of protein. Treatment with insulin was effective in improving the degradative capacity at both pH levels. We suggest that decreased proteinase activity in diabetic glomeruli may, at least partly, explain the glomerular protein accumulation in diabetic nephropathy.