Affiliation:
1. Departments of Medicine and Pathology, University of Massachusetts Medical School Worcester, Massachusetts
Abstract
The spontaneously diabetic BioBreeding/Worcester (BB/W) rat was used to examine the role of glycemie control in the pathogenesis of diabetic glomerulopathy and proteinuria. Nondiabetic BB/W rats (group 1) were compared with moderately (group 2) and severely (group 3) hyperglycemie diabetic animals of similar age. Urinary protein excretion and morphometric measurements of glomerular basement membrane (GBM) width and mesangial area were performed after 4, 8, and 12 mo of study.
At 4 mo, urinary protein excretion both in group 2 (9.3 ± 0.7 mg/24 h) and group 3 (24.8 ± 1.98 mg/24 h) exceeded that in group 1 (5.4 ± 0.6 mg/24 h; P < .05). Moreover, proteinuria in group 3 was significantly greater than in group 2 (P < .05). In addition, proteinuria increased in group 3 animals between 4 and 12 mo of study but did not advance in groups 1 or 2.
GBM width in both diabetic groups (168.8 ± 2.4 and 165.7 ± 2.2 nm, groups 2 and 3, respectively) exceeded that in group 1 (148.3 ± 3.8 nm; P < .01) by 4 mo. At 12 mo, severely hyperglycemie group 3 animals had significantly greater GBM thickening than group 2. GBM width increased in all three groups over the course of study, but the rate of growth did not differ between groups 1 and 2. However, the rate of growth in group 3 was greater than in either group 1 or group 2. Urinary protein excretion correlated significantly with GBM width in diabetic rats. No differences in proportional mesangial area or the proportional area made up of mesangial matrix or cytoplasm could be found among the three groups.
In the spontaneously diabetic BB/W rat, poor glycemie control contributes to both proteinuria and GBM widening but apparently does not cause mesangial expansion. Proteinuria and GBM widening may either be interdependent or related to a common third factor in the diabetic milieu.
Publisher
American Diabetes Association
Subject
Endocrinology, Diabetes and Metabolism,Internal Medicine
Cited by
27 articles.
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