Abstract 12369: Distributional Changes of Glomerular Slit Membrane Components and Widening of Inter-foot Process Spaces in Early Diabetic Rats
We have visualised the early augmented glomerular filtration in-vivo that may be related to the development of diabetic nephropathy with albuminuria by multi-photon microscopy. We hypothesised that there are structural and component protein distributional changes, which may be associated with albuminuria. We used control rats and streptozotocin-induced diabetic Wistar rats of 1 to 6 months (n=2 & 10). After kidneys were extracted, slit membrane component proteins, such as nephrin, podocin and CD2AP of sliced samples were dyed for the study. Stained images of each component were binarised and the distributions of slit membrane proteins were analysed by area ratio (ratio of coexisting area of two component proteins). In control rats, all these components were coexisting distributed homogenously. Area ratio was found decreasing linearly with diabetic duration. Amongst pair combinations of 3 proteins, the best correlation was between the diabetic duration and the area ratio of nephrin and podocin (r=0.871, Fig.1). This means discrepancy of slit membrane protein distribution deteriorates progressively. As for electron micsoscopic images (x 50,000), triangle inter-footprocess area from the root of podocytes and the centre of the gap was compared between the control (n=10) and diabetic rats (n=23) after normalisation by gap length. It was found that triangle area was significantly larger for diabetic rats than for control (p<0.01, Fig.2). Taken together, in early diabetic rats, there are distributional changes of slit membrane proteins and structural widening of inter-footprocess spaces. They may attribute to mild albuminuria at the early stage of diabetes.
- © 2012 by American Heart Association, Inc.