Initial ultrastructural changes in pore size and anionic sites of the glomerular basement membrane in Streptozotocin-induced diabetic rats and their prevention by insulin treatment

Background/Aim: The present study was conducted to elucidate the mechanism( s) of the development of early diabetic nephropathy, examining ultrastructu ral changes employing electron microscopy, especially changes in pore size of the glomerular basement membrane (GBM) of streptozotocin (STZ)-induced d iabetics rats. Methods: Urinary albumin excretion rate (UAE), pore size of the lamina densa of the GEM visualized directly by the tissue negative stai ning method, and number of anionic sites (AS) in the corresponding portion of the lamina rara externa were determined for 6 weeks in diabetic rats wit hout and with insulin treatment. Results: The UAE of the diabetic rats incr eased with time and was significantly greater than that of the nondiabetic control rats after 4 weeks (p < 0.01), while insulin treatment suppressed t he increased UAE of diabetic rats. The median values in both short diameter and long dimension of the pores in the diabetic group were markedly increa sed at the 2nd week as compared with those in the nondiabetic control rats, whereas no significant change was found in the pore size of the diabetic r ats with insulin treatment. Moreover, the number of AS in the GEM of the di abetic rats was significantly (p < 0.001) decreased from the 2nd week onwar d. Insulin treatment also prevented a decrease in AS number in diabetic rat s. Conclusions: It is suggested from these results that an impairment of ba rrier size selectivity occurs at a very early stage of STZ-induced diabetes in rats, which may enhance the abnormality of the charge-selective propert ies of the GEM. In addition, insulin treatment may protect this barrier sys tem through normalizing blood glucose control in STZ-diabetic rats.