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
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.