Reduced number of anionic sites is associated with glomerular basement membrane thickening in the diabetic BB-rat

Abstract

Summary. Glomerular basement membranes of diabetic and age-and sex-matched non-diabetic BB rats were studied morphometrically and ultrastructurally using a quantitative histochemical technique employing the cationic dye cuprolinic blue. Six months of diabetes resulted in a significant reduction in the density of anionic sites associated with increased thickness of the glomerular basement membrane. These findings suggest that loss of anionic sites may be an important mechanism in the genesis of glomerular basement membrane dysfunction in diabetes.

Reduction of heparan sulphate-associated anionic sites in the glomerular basement membrane of rats with streptozotocin-induced diabetic nephropathy

“…This was also found by Vernier et al in the kidneys of insulin-dependent diabetic pati ents and by Chakrabarti el al [31 ] in the kidneys of di abetic BB-rats. The results show that in the LRE of rately and differently.…”

Significant glomerular basement membrane thickening in hyperglycemic and normoglycemic diabetic‐prone BB Wistar rats

“…In the current study, GBM anionic sites were characterized as heparan sulfate proteoglycan and their densities were similar in BB/DP h and age-matched controls. These results varied from those of several investigators, including Chakrabarti and Sima (1989), who demonstrated significantly reduced site density using the cationic dye cuprolinic blue in 6-month diabetic BB rats. Likewise, significant reductions in PEI or cuprolinic blue labeling have been demonstrated in streptozotocin-induced diabetic rats at up to 8 months of diabetes (Moriya et al, 1993;van den Born et al, 1995a).…”

“…Our morphometric data also showed that GBMs in BB/DP h animals were significantly thicker than age-matched BB/DR controls at 3 months, 6 months, and 1 year postonset of hyperglycemia. This was also not unexpected as other investigators showed that as early as 6 months postonset of hyperglycemia, GBMs in BB/DP rats were thicker than age-matched BB/DR rats (Brown et al, 1983;Cohen et al, 1987;Chakrabarti and Sima, 1989;Feld et al, 1995). Also, Feld et al (1995) showed that at 1 year, GBMs were 25% wider in BB/DP rats than in age-matched BB/DR controls.…”

“…However, our PEI staining procedures differ from those utilizing cuprolinic blue (Chakrabarti and Sima, 1989;van den Born et al, 1995a) and the cationicity of these two probes may not be identical. Moreover, the studies were carried out at disparate times postonset of hyperglycemia.…”

Reduction of heparan sulphate-associated anionic sites in the glomerular basement membrane of rats with streptozotocin-induced diabetic nephropathy

“…We have recently demonstrated the induction of an acute selective proteinuria after intra venous injection of a monoclonal antibody against GBM HS [9], Diabetic nephropathy ultimately develops in 30-40% of patients suffering from insulin-dependent di abetes mellitus and is initially characterized by micro- [29], A recent study using cuprolinic blue demonstrated a reduction of HS-associated anionic sites within the GBM in patients with diabetic neph ropathy, which was inversely correlated with the de gree of albuminuria [30]. A decrease of the number and density of cuprolinic blue anionic sites in the GBM of diabetic BB-rats has also been demon strated [31], In this study we analysed the HS-associated anionic sites in the GBM of STZ-diabetic rats with a pronounced albuminuria.…”