Department of Physiology, Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA.
Am J Physiol Renal Physiol. 2011 Mar;300(3):F618-25. doi: 10.1152/ajprenal.00421.2010. Epub 2010 Dec 8.
Diabetic nephropathy is a major cause of end-stage renal disease worldwide. The current studies were performed to determine the later stages of the progression of renal disease in type II diabetic mice (BKS; db/db). Methodology was developed for determining glomerular filtration rate (GFR) in conscious, chronically instrumented mice using continuous intravenous infusion of FITC-labeled inulin to achieve a steady-state plasma inulin concentration. Obese diabetic mice exhibited increased GFR compared with control mice. GFR averaged 0.313 ± 0.018 and 0.278 ± 0.007 ml/min in 18-wk-old obese diabetic (n = 11) and control (n = 13) mice, respectively (P < 0.05). In 28-wk-old obese diabetic (n = 10) and control (n = 15) mice, GFR averaged 0.348 ± 0.030 and 0.279 ± 0.009 ml/min, respectively (P < 0.05). GFR expressed per gram BW was significantly reduced in 18- and 28-wk-old obese diabetic compared with control mice (5.9 ± 0.3 vs. 9.0 ± 0.3; 6.6 ± 0.6 vs. 7.8 ± 0.3 μl·min(-1)·g body wt(-1)), respectively (P < 0.05). However, older nonobese type II diabetic mice had significantly reduced GFR (0.179 ± 0.023 ml/min; n = 6) and elevated urinary albumin excretion (811 ± 127 μg/day) compared with obese diabetic and control mice (514 ± 54, 171 ± 18 μg/day), which are consistent with the advanced stages of renal disease. These studies suggest that hyperfiltration contributes to the progression of renal disease in type II diabetic mice.
糖尿病肾病是全球范围内导致终末期肾病的主要原因。本研究旨在确定 II 型糖尿病小鼠（BKS；db/db）肾脏疾病进展的后期阶段。方法是为在清醒、长期仪器化的小鼠中使用 FITC 标记的菊粉进行连续静脉输注，以达到稳定的血浆菊粉浓度，从而确定肾小球滤过率（GFR）。与对照小鼠相比，肥胖型糖尿病小鼠的 GFR 增加。18 周龄肥胖型糖尿病（n = 11）和对照（n = 13）小鼠的 GFR 平均值分别为 0.313 ± 0.018 和 0.278 ± 0.007 ml/min（P < 0.05）。在 28 周龄肥胖型糖尿病（n = 10）和对照（n = 15）小鼠中，GFR 平均值分别为 0.348 ± 0.030 和 0.279 ± 0.009 ml/min（P < 0.05）。与对照小鼠相比，18 周龄和 28 周龄肥胖型糖尿病小鼠的 GFR 每克体重表达显著降低（分别为 5.9 ± 0.3 与 9.0 ± 0.3；6.6 ± 0.6 与 7.8 ± 0.3 μl·min(-1)·g body wt(-1)）（P < 0.05）。然而，年龄较大的非肥胖型 II 型糖尿病小鼠的 GFR 显著降低（0.179 ± 0.023 ml/min；n = 6）和尿白蛋白排泄量升高（811 ± 127 μg/天），与肥胖型糖尿病和对照小鼠相比（514 ± 54，171 ± 18 μg/天），这与肾脏疾病的晚期阶段一致。这些研究表明，高滤过导致 II 型糖尿病小鼠肾脏疾病的进展。
