title: Glomerular filtration rate determinations in conscious type II diabetic mice.
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.
authors.affiliation: Department of Physiology, Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA.
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Bivona
authors.forename: Sungmi
authors.initials: S
authors.lastname: Park
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Harrison-Bernard
mesh_terms: D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000503:physiopathology*; D003928:Diabetic Nephropathies / Q000378:metabolism / Q000503:physiopathology*; D004195:Disease Models, Animal; D018450:Disease Progression; D005919:Glomerular Filtration Rate / Q000502:physiology*; D007444:Inulin / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009765:Obesity / Q000378:metabolism / Q000503:physiopathology*; D010953:Plasma Volume / Q000502:physiology; D054411:Receptors, Leptin / Q000172:deficiency / Q000235:genetics / Q000378:metabolism
chemical_list: D054411:Receptors, Leptin; D007444:Inulin