Increased peritoneal permeability to albumin in streptozotocin diabetic rats

The mechanism behind the increased peritoneal permeability to albumin in diabetics is still unclear. In this study, streptozotocin diabetic rats developed albuminuria and significantly increased D/P of albumin after the fourth week of disease, reaching peak levels at the end of the 24 week period of follow-up. Coincidentally, extravasation of albumin to the interstitial tissue was evaluated with the Evans-blue method. Age-matched control rats showed Evans-blue concentrations of 0.023 +/- 0.013 micrograms/100 mg of dry tissue, whereas in diabetics the numbers were 1.22 +/- 0.719 micrograms (P < 0.001). Perfusion with Ruthenium-Red (RR) done in control at zero time, and in age-matched intact as well as in diabetic rats after 24 weeks of disease showed that the density distribution of capillary subendothelial anionic sites was significantly lower for diabetics (13 +/- 3/microns basement membrane vs. 31 +/- 3 and 34 +/- 4 in control groups; P < 0.001). Similar findings were made on the mesenteric submesothelial basement membrane. Mean density of RR decorated anionic sites was 12 +/- 2/microns basement membrane in diabetics, whereas those observed in both control groups were 31 +/- 2 and 31 +/- 3/microns (P < 0.001). Therefore, this reduced density of microvascular and submesothelial negative charges, equivalent to that induced by diabetes in other capillary beds, appears to be at the origin of the decreased permselectivity of the diabetic peritoneum for anionic serum albumin.