Non-enzymatic glycation and altered renal structure and function in the diabetic rat

Abstract

Renal function parameters including creatinine clearance, urinary albumin excretion, basement membrane thickening, and levels of non-enzymatic glycation of glomerular basement membrane were studied in rats rendered diabetic with streptozotocin. Diabetic animals had elevated, glycated hemoglobin levels (P < 0.05), increased creatinine clearance, and urinary albumin excretion rates (P < 0.05) as compared to insulin treated diabetic (euglycemic), age-matched, and streptozotocin non-diabetic animals. The level of non-enzymatic glycation of glomerular basement membrane was significantly elevated (P < 0.05) in the diabetic animals as well, with the level of non-enzymatic glycation of all animals, correlating (P < 0.05) to the average blood glucose level of each animal. Despite changes in functional parameters, and increased levels of non-enzymatic glycation between the diabetic and euglycemic animals, there was no difference in glomerular basement membrane thickness between the two groups. However, there was a difference between all diabetic euglycemics and the age-matched control animals. We hypothesized that increased glycation of glomerular basement membrane may alter renal function, possibly by affecting the net change of the glomerular filtration barrier. However, glomerular basement membrane thickening per se does not affect the functional change which have been observed, thus casting doubt upon its role in the development of diabetic nephropathy.