A stereological study of the renal glomerular vasculature in the db / db mouse model of diabetic nephropathy

In diabetic nephropathy, glomerular hypertrophy is evident early in response to hyperglycaemia. Alterations of capillary length and vascular remodelling that may contribute to glomerular hypertrophy and the subsequent development of glomerulosclerosis remain unclear. The present study used the db/db mouse model of Type 2 diabetes to examine the glomerular microvascular changes apparent with long-term diabetic complications. Unbiased stereological methods and high-resolution light microscopy were used to estimate glomerular volume, and glomerular capillary dimensions including length and surface area in 7-month-old db/db diabetic mice and age-matched db/m control mice. The db/db diabetic mice showed significant glomerular hypertrophy, corresponding with elevated blood glucose levels, and increased body weight and kidney weight, compared with db/m control mice. Glomerular enlargement in db/db mice was associated with increases in the surface area (5.387 ± 0.466 × 10 4 μ m 2 vs. 2.610 ± 0.287 × 10 4 μ m 2 ; P < 0.0005) and length (0.3343 ± 0.022 × 10 4 μ m vs. 0.1549 ± 0.017 × 10 4 μ m; P < 0.0001) of capillaries per glomerulus, compared with non-diabetic mice. Stereological assessment at the electron microscopic level revealed increased glomerular volume density of mesangial cells and mesangial matrix, and thickening of the glomerular basement membrane in db/db mice. These results demonstrate that glomerular hypertrophy evident in advanced diabetic nephropathy in this model is associated with increased length and surface area of glomerular capillaries. The contribution of angiogenesis and vasculogenesis to the glomerular microvascular alterations in response to hyperglycaemia remain to be determined.