Fig. 4.

STZ-treated NPY^−/− mice are protected from albuminuria and podocyte damage. Diabetes was induced in male NPY knockout (NPY^−/−) 129/Sv and WT 129/Sv mice aged 6 to 8 wk with i.p. injections of 50 mg/kg STZ dissolved in sodium citrate buffer (pH 4.5) for 5 consecutive days. Tissue was collected 24 wk after administration of STZ. (A) Nonfasted blood glucose was significantly higher in both WT and NPY^−/− animals from 8 wk after STZ injection; ***P < 0.001, with no differences between the two diabetic groups. (B) A significant increase in the uACR in STZ-treated WT mice 24 wk after injection. *P = 0.036 WT STZ (n = 10) vs. WT Citrate (n = 4), no significant increase in STZ-treated NPY^−/− animals (n = 8) when compared with NPY^−/− citrate-treated mice (n = 5). (C) PAS staining presented evidence of sclerosis in some glomeruli of each diabetic cohort, and small protein casts could be seen in tubules of each model (black arrow). (Scale bar, 25 μm.) (D) Electron microscopy (EM) images of STZ-treated WT and NPY^−/− mice. (Scale bar, 500 nm.) (E) Quantification of podocyte FP width as a measurement of effacement; n = 3 mice per experimental group, >20 regions per mouse; **P < 0.01.