Simvastatin (SMV) ameliorates the progression of diabetic glomerulopathy in type 2 diabetes mellitus (DM) mice

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