Renal proteinases and kidney hypertrophy in experimental diabetes.
IDDM is associated with an increase in kidney size, which is due to cellular hypertrophy and progressive matrix accumulation within the glomerulus and throughout the tubulo-interstitium. The present study addressed the potential role of cysteine and metalloproteinases in renal hypertrophy of short-term diabetes. Three weeks after induction of streptozotocin diabetes in rats, intraglomerular gelatinase activity (streptozotocin: 23 +/- 4 vs control: 44 +/- 3 mU/microgram DNA) and cathepsin L+B activity (streptozotocin: 6.7 +/- 0.8 vs control: 9.3 +/- 0.7 U/microgram DNA) were significantly decreased. Insulin treatment completely prevented the decline in glomerular proteinase activity (gelatinase: 37 +/- 6 mU/microgram DNA; cathepsin L+B: 9.6 +/- 0.9 U/microgram DNA). In isolated proximal tubules a similar pattern of enzyme activity could be observed. Three weeks of diabetes caused a significant decline in cathepsin L+B activity (streptozotocin: 28 +/- 2 vs control: 37 +/- 3 U/microgram DNA). Insulin treatment again prevented the decline in these tubular proteinase activities. In parallel, kidney weight increased by 22% and glomerular protein/DNA ratio rose by 17% in untreated diabetic rats. Diabetic rats receiving insulin displayed a normal glomerular protein/DNA ratio and the kidney weight was increased by only 5%. These results show that renal hypertrophy of early diabetes is closely associated with a decline in both glomerular and tubular proteinase activity. Adequate insulin substitution prevented renal hypertrophy and the reduction in proteinase activity.
Schaefer
L
L
Department of Nephrology, University of Wuerzburg, Germany.
Schaefer
R M
RM
Ling
H
H
Teschner
M
M
Heidland
A
A
D000818:Animals; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology*; D006984:Hypertrophy; D007328:Insulin / Q000378:metabolism; D007668:Kidney / Q000201:enzymology* / Q000473:pathology*; D007678:Kidney Glomerulus / Q000201:enzymology; D007684:Kidney Tubules / Q000201:enzymology; D008297:Male; D008666:Metalloendopeptidases / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D007328:Insulin; D003546:Cysteine Endopeptidases; D008666:Metalloendopeptidases