STZ-INDUCED DIABETES RESULTS IN DECREASED ACTIVITY OF GLOMERULAR CATHEPSIN AND METALLOPROTEASE IN RATS

Citation
Jf. Reckelhoff et al., STZ-INDUCED DIABETES RESULTS IN DECREASED ACTIVITY OF GLOMERULAR CATHEPSIN AND METALLOPROTEASE IN RATS, Diabetes, 42(10), 1993, pp. 1425-1432
Citations number
42
Categorie Soggetti
Endocrynology & Metabolism","Medicine, General & Internal
Journal title
ISSN journal
00121797
Volume
42
Issue
10
Year of publication
1993
Pages
1425 - 1432
Database
ISI
SICI code
0012-1797(1993)42:10<1425:SDRIDA>2.0.ZU;2-1
Abstract
IDDM in humans and STZ-induced diabetes in rats are both characterized in the early phase of the disease by glomerular hypertrophy; and, in the chronic phase of the disease, by mesangial expansion and glomerula r basement membrane thickening. Decreases in glomerular intracellular protein degradation rates in diabetic individuals could contribute to the glomerular hypertrophy by allowing a build-up of cellular protein. Decreases in extracellular protease activity could contribute to the build-up of matrix protein in the mesangium and glomerular basement me mbrane. In this study, the levels of lysosomal cathepsin activities an d glomerular metalloprotease activities were measured in isolated glom erular homogenates from STZ-induced diabetic rats at 4 days and 5 wk a fter administration of the drug. Some of the rats in the 5-wk study we re treated with dally insulin; others were untreated. After 4 days of diabetes, cathepsin B and L activities were decreased by 15-45% when c orrelated with the levels of glomerular protein or DNA. Gomerular meta lloprotease activity was decreased by 75% in the diabetic rats when co mpared with controls. After 5 wk of diabetes, cathepsin activities eit her were unchanged (for cathepsin B and L together or cathepsin S) or increased (cathespin B alone) in insulin-treated diabetic rats, and co ntinued to be decreased in untreated diabetic rats. A 40-50% decrease in glomerular metalloprotease activity continued in both diabetic grou ps. These data strongly suggest that decreases in the lysosomal cathep sin activities may contribute to IDDM-induced glomerular cellular hype rtrophy. The data further indicate that a decrease in glomerular metal loprotease activity may contribute to diabetes-induced mesangial expan sion and glomerular basement membrane thickening. The decrease in glom erular metalloprotease activity may be attributable to a decrease in m etalloprotease synthesis or to an increase in endogenous tissue inhibi tor of metalloprotease.