Glomerular filtration rate determinations in conscious type II diabetic mice

Am J Physiol Renal Physiol. 2011 Mar;300(3):F618-25. doi: 10.1152/ajprenal.00421.2010. Epub 2010 Dec 8.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Diabetes Mellitus, Type 2 / metabolism
  • Diabetes Mellitus, Type 2 / physiopathology*
  • Diabetic Nephropathies / metabolism
  • Diabetic Nephropathies / physiopathology*
  • Disease Models, Animal
  • Disease Progression*
  • Glomerular Filtration Rate / physiology*
  • Inulin / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Obesity / metabolism
  • Obesity / physiopathology*
  • Plasma Volume / physiology
  • Receptors, Leptin / deficiency
  • Receptors, Leptin / genetics
  • Receptors, Leptin / metabolism

Substances

  • Receptors, Leptin
  • Inulin