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Simvastatin (SMV) ameliorates the progression of diabetic glomerulopathy in type 2 diabetes mellitus (DM) mice
Author(s) -
WEI PEILIN,
WANG XIAOXIA,
Grimm P. Richard,
SANSOM STEVEN C.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a335
Subject(s) - medicine , endocrinology , nephrin , diabetic nephropathy , podocin , triglyceride , type 2 diabetes mellitus , insulin , simvastatin , cholesterol , diabetes mellitus , podocyte , proteinuria , kidney
Studies indicate that SMV confers renoprotection in a variety of glomerular diseases. We hypothesized that SMV might decelerate or reverse the progression of nephropathy,in type 2DM, induced in male C57BL/6 mice by feeding a high fat diet (HF, 45 kcal% fat). After 22 weeks on HF, 9 type 2 DM mice were treated with SMV (7 μg/day/gBW) via subcutaneous osmotic mini‐pump for 4 wks. Another 11 type 2 DM mice (HF‐veh) and 13 agesmatched mice on a normal diet (ND‐veh) were vehicle controls. Body weight, fasting blood glucose, insulin and lipids were evaluated before and after SMV treatment. At the end of treatment, glomerular morphology and function were evaluated. The diabetic mice weighed more and had significantly elevated fasting blood glucose, insulin, cholesterol and triglyceride levels; however, except for cholesterol, these values in HF‐SMV were not different compared with HF‐veh. 24‐hour urinary albumin excretion (UAE) was reduced in HF‐SMV (before and after: 75.4 ± 22.1 vs 45.4 ± 10.2 μg /day) and ND‐veh (25.5 ± 4.4 vs 15.8 ± 0.9 μg /d), but not in HF‐veh (43.7 ± 13.7 vs 69.7 ± 22.5 μ g /d). The alteration in UAE of HF‐veh mice (24.2 ± 10.3 μg /d) was significantly different (p<0.05, one‐way ANOVA) in comparison to HF‐SMV (−30.2 ± 18.0 μg /d) and ND‐veh (−8.7 ± 4.8 μg /d). Podocyte damage was determined by immuno‐staining of nephrin, a podocyte specific protein. The number of nephrin stained capillary loops in glomeruli was significantly decreased in HF‐veh (1.9 ± 0.7) compared with ND‐veh (5.4 ± 0.9) and significantly increased back to control levels in HF‐SMV (4.4 ± 0.5). Conclusion: SMV may decelerate UAE and reverse damage to podocytes in Type 2 DM mice.