Reduction of leucocyte proteolytic enzyme activity in diabetic patients with microalbuminuria and proteinuria: its possible role in diabetic nephropathy.
Mesangium enlargement and glomerular basement membrane thickening are cardinal features of diabetic nephropathy. The reasons for these changes are uncertain but decreased degradation of extracellular matrix may play a role. Mesangium degradation can be modulated by factors intrinsic to the kidney or by factors in the circulation. In this study the capacity of leucocyte proteolytic enzymes to degrade mesangium matrix materials was investigated. Leucocytes were obtained from 57 patients with NIDDM (age 58.3 +/- 8.8 years, duration 9.4 +/- 7.3 years, body mass index (BMI) 30 +/- 6 kg m-2, HbA1c 7.7 +/- 2.0%) and 21 control subjects (age 55.1 +/- 14.6 years, BMI 25 +/- 4 kg m-2). Leucocyte lysates from control and NIDDM subjects with normal AER degraded matrix to the same extent (40.6 +/- 8.2% vs 42.9 +/- 13.5%) while lysates from patients with microalbuminuria and proteinuria were less able to degrade matrix (33.0 +/- 14.2% and 26.1 +/- 12.7%, respectively). There was a significant inverse correlation between matrix degradation and AER (r = -0.49) and multiple regression analysis showed that AER was the most important factor determining degradation rate (R2 = 0.24). Degree of metabolic control, age, and blood pressure were not significant factors. The major enzyme(s) responsible for the matrix degradation was identified as metalloproteinase(s). We conclude that leucocytes from diabetic patients with abnormal albumin excretion have a decreased proteolytic capacity to degrade extracellular matrix. This may play a role in the glomerular basement membrane thickening and mesangium expansion which occurs in diabetic nephropathy.
McLennan
S V
SV
Department of Endocrinology, Royal Prince Alfred Hospital, Sydney, Australia.
Zilkens
R R
RR
Yue
D K
DK
Turtle
J R
JR
D000419:Albuminuria / Q000209:etiology / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000378:metabolism*; D003928:Diabetic Nephropathies / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D005920:Glomerular Mesangium / Q000378:metabolism*; D006801:Humans; D007962:Leukocytes / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D010447:Peptide Hydrolases / Q000378:metabolism*; D012044:Regression Analysis
D010447:Peptide Hydrolases