title: Renal proteinases and kidney hypertrophy in experimental diabetes.
abstract: 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.
authors.affiliation: Department of Nephrology, University of Wuerzburg, Germany.
authors.forename: L
authors.initials: L
authors.lastname: Schaefer
authors.forename: R M
authors.initials: RM
authors.lastname: Schaefer
authors.forename: H
authors.initials: H
authors.lastname: Ling
authors.forename: M
authors.initials: M
authors.lastname: Teschner
authors.forename: A
authors.initials: A
authors.lastname: Heidland
mesh_terms: 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
chemical_list: D007328:Insulin; D003546:Cysteine Endopeptidases; D008666:Metalloendopeptidases