The number of podocyte and slit diaphragm is decreased in experimental diabetic nephropathy

Abstract

PURPOSE: To determine the number of podocyte, slit diaphragms, slit diaphragm extensions and GBM thickness in diabetic nephropathy. METHODS: Sixty "Rattus Wistar"of both sexes weighing 200-300g were divided in two experimental groups: normal group 10 animals, and alloxan diabetic rats - 50 animals. Alloxan was administered in a single IV dose of 42mg/kg body weight. Body weight, water and food intake, diuresis, and blood and urine glucose were determined in both groups before alloxan injection and two weeks, six and twelve months after alloxan injection. Proteinuria was measured at 12 months in both groups. After 12 months animals were sacrificed, and the right kidney processed for electron microscopy. RESULTS: Clear clinical and laboratory signs of severe diabetes were seen, in all alloxan-diabetic rats at all follow-up times. Glomerular basement membrane (GBM) thickening, podocyte number, and slit diaphragm number and extension were determined. GBM of all diabetic rats was significantly thicker (median=0.29µm; semi-interquartile range=0.065µm) than in the normal rats (0.23µm; 0.035µm). Diabetic rat podocyte number (8; 1), slit diaphragm number (4; 1), and slit diaphragm extension (0.021µm; 0.00435µm) were significantly lower than in normal rats (11; 1) and (7; 1.5), and (0.031µm; 0.0058µm). Diabetic rat proteinuria (0.060mg/24h; 0.037mg/24h) was higher than in normal rats (0.00185mg/24h; 0.00055mg/24h). CONCLUSION: Experimental diabetes is associated with significant (p<0.05) changes in podocyte foot process, slit number, slit diaphragm extension, and GBM thickness.

The potential beneficial effects of ethyl pyruvate on diabetic nephropathy: an experimental and ultrastructural study

“…GBM thickness increases from 6 months after diabetes induction, and its long-term increase in diabetic rats has been previously reported by Lerco et al [29]. Our study lasted for two weeks, compared with six months in the study of Lerco et al [29].…”

“…Our study lasted for two weeks, compared with six months in the study of Lerco et al [29]. In our study there was no significant decrease in the thickness of the basal membrane in the DM + EP group, which led us to wonder whether non-treatment of GBM thickening totally with EP may be the effect of a long lasting complication of STZ induction.…”

“…The mechanism of glomerular pathology underlying in DN is still unclear [27]. There is evidence showing that diabetic nephropathy results from metabolic alterations that occur in the renal glomeruli after long exposure to high glycaemic levels [28,29]. In addition to the haemodynamic effects, several non-haemodynamic factors have been identified to be involved in the pathogenesis of DN [27].…”

Reduction of podocytes number in late diabetic alloxan nephropathy: prevention by glycemic control

“…The role of glycemic control in renal lesions was investigated herein. In a previous work, we used electron microscopy to study alloxan diabetic rats for 48 weeks, and demonstrated the presence of significant proteinuria, reduction in podocyte number, and increased GMB thickness 6 . In this study, glycemic control attenuated glomerular changes; GBM thickness was not so intense 6 and 12 months after diabetes induction and the podocyte number at 12 months was similar to that in normal animals when continuously using insulin combined with an oral antihyperglycemiant.…”

“…Reduced podocyte number has been seen after 6 months in rats with streptozotocin (STZ)-induced diabetes, compared with normal rats 4,5 . In alloxan diabetic rats an evident podocyte reduction has been observed concomitantly with an increased excretion of protein in urine 12 months after induction 6 . There is an inverse relationship between glucose homeostasis an renal damage 7,8 .…”