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16 Glomerular basement membrane selective permeability in streptozotocin-induced diabetic rats.

In diabetes, the glomerular basement membrane (GBM) undergoes thickening and structural alterations with loss of glomerular permselectivity properties. However, the onset of the alterations at early phases of diabetes is unclear. Aiming to determine the functional and structural alterations of the glomerular wall in the early stages of diabetes, we have studied the distribution of endogenous circulating albumin and type IV collagen in the GBM using the immunocytochemical approach. GBM thickness was also measured as an additional parameter for revealing structural changes. The streptozotocin-injected hyperglycemic rat was our animal model and renal tissues were examined after 10 days, 2, 4 and 6 months of hyperglycemia. The immunogold technique was applied with specific antibodies followed by protein A-gold. Results were analyzed by morphometry. Glomerular permeability to endogenous albumin was significantly altered as early as upon ten days of hyperglycemia. In contrast, no structural modifications were detected at this time point. Indeed, GBM thickening and an altered type IV collagen distribution were only observed after four months of hyperglycemia. These results suggest that functional alterations take place early in diabetes prior any structural modification. In order to evaluate the reversibility of the glomerular alterations, the two-months old diabetic animals were treated with insulin. These animals showed a significant restoring of their glomerular permselectivity. Controlling hyperglycemia by insulin leads to a decrease of non-enzymatically glycated serum proteins that have been shown to induce glomerular hyperfiltration. Our results suggest a link between glycemic levels and alteration of permeability in the early phases of diabetes, probably through high levels of glycated serum proteins. Supported by the Medical Research Council of Canada.

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