Development of glomerular lesions in experimental long-term diabetes in the rat

Abstract

Exact parameters for relevant glomerular structures in the course of streptozotocin diabetes in rats with 1 to 18 months' duration were obtained with stereological methods. Renal cortical tissue from diabetic (D) and control animals (C) was processed for light- and electron microscopy and measurements were performed on systematically sampled glomeruli. The thickness of the basement membrane (BM) increased with age in both groups, but the rate of increase was 50% higher in D: 19 +/- 1.2 nm/month (mean +/- SD) vs. 13 +/- 0.9 nm/month, P = 0.0003. The time course of other structural quantities was characterized by the acute changes constituting the glomerular hypertrophy, earlier shown to develop within the first few days of diabetes. All these changes were confirmed in the present study: In the earliest phase the diabetic rats showed an increased total volume of glomeruli, mesangium, and mesangial BM material, as well as an increased surface of the capillary walls. However, none of these differences between the groups showed progression with increasing duration. Mesangial changes corresponding to those of the glomerulopathy in long-term diabetes were not demonstrable within the experimental period. The streptozotocin diabetic rat, therefore, is not useful as a model of advanced diabetic glomerulopathy. But the BM thickness follows the same predictable time course as in human diabetes insofar as moderately advanced cases are concerned. BM thickness is the parameter of choice when a potential effect of different variables on the development of diabetic glomerulopathy is under study.

Alteration in the distribution of type IV collagen in glomerular basal laminae in diabetic rats as revealed by immunocytochemistry and morphometrical approach

“…The glomerular basal laminae of the streptozotocin diabetic animals investigated in the present study were markedly thickened and our subjective and morphometric results are in total agreement with those reported previously [3,5]. The labelling obtained for type IV collagen over the thickened glomerular basal laminae of the diabetic animals was preferentially located on the subendothelial side of the laminae and this was further confirmed by the morphometrical evaluation.…”

“…These alterations constitute the characteristic features of diabetic microangiopathy [1]. While the morphological thickening of basal laminae has been well documented in various tissues [2][3][4][5][6], the biochemical and functional alterations, which concern the composition of basal lamina material and the loss of the filtration selectivity, accompanied by an increase in capillary permeability, have been well described only for the glomerulus and for a preparation of isolated capillaries [7][8][9][10][11][12]. However, a controversy has been raised concerning the biochemical changes occurring in the diabetic glomerular basal laminae [13].…”

Alterations of the Rat Mesentery Vasculature in Experimental Diabetes

“…No thickening of the basement membrane was observed in our model (animals at 3 months of diabetes). This does not contradict the current knowledge, as the accumulation of material in this structure becomes visible at later stages of the disease (Bendayan et al, 1986;Doucet et al, 2000;Hirose et al, 1982;Østerby, 1986). The rather uniform distribution of 125 I-DNP- Localization of DNP-BSA across the mesothelial basement membrane in the mesentery of (a) control and (b) diabetic rats.…”

TGF-β1–Induced Glomerular Disorder Is Associated with Impaired Concentrating Ability Mimicking Primary Glomerular Disease with Renal Failure in Man

“…The area of the peripheral capillary surface (the glomerular filtration surface) is the structural determinant of the GFR (Hirose et al, 1980). The area of the Parameters of the glomerular filtration rate.…”

“…On the subsample photographed at higher magnification (21,900ϫ), point counting was used to estimate the volume fractions of mesangial space and mesangial matrix: V V (mes/tuft) and V V (matrix/mes). Further, BMT was estimated with the orthogonal intercept method (Hirose et al, 1982). The methods with the digitalized system (2-month group) were analogous.…”