Diabetologie und Stoffwechsel 2015; 10 - P64
DOI: 10.1055/s-0035-1549570

L-Carnosine attenuates the development of diabetic nephropathy in the BTBR ob/ob mouse model

T Albrecht 1, M Schilperoort 2, S Zhang 1, BK Krämer 1, W Kriz 3, J Van den Born 4, H Baelde 2, E De Heer 2, BA Yard 1, SJ Hauske 1
  • 1University Medical Center Mannheim, Vth Department of Medicine (Nephrology/Endocrinology/Rheumatology), Mannheim, Germany
  • 2Leiden University Medical Center, Department of Pathology, Leiden, Netherlands
  • 3Medical Faculty Mannheim, Institute of Neuroanatomy, Mannheim, Germany
  • 4University Medical Center Groningen, Department of Internal Medicine (Nephrology), Groningen, Netherlands

Diabetic nephropathy (DN) is the most frequent cause for end-stage renal failure (ESRF) worldwide. It's pathophysiology is multi-factorial and current therapeutic options only retard the progression of DN. We hypothesize that L-Carnosine, a natural anti-oxidant and pH-stabilizing dipeptide, may be an alternative therapeutic compound for preventing or retarding the development of DN.

Male BTBR ob/ob mice (n = 15) were supplemented with L-Carnosine (4 mmol/l) for 18 weeks. Fasting plasma glucose (FPG), weight and drinking volume were determined weekly. At week 24, blood and urinary samples were collected. All mice were fixed through vascular perfusion followed by histological and immunohistochemical tissue examination.

Treatment with L-Carnosine significantly improved metabolic control, by reduced FPG (p = 0,005) and HbA1c (p = 0,02) levels. The drinking volume was lower than in the control group (p < 0,01), suggesting less pronounced osmotic diuresis. Proteinuria assessed by urinary albumin-to-creatinine ratio was nearly halved in the treatment group (p < 0,001). Although L-Carnosine did not affect podocyte number, it significantly ameliorated renal corpuscle hypertrophy, indicating diminished hyperfiltration. Kidney weights were also lower in the treated arm (p < 0,05). Fibronectin distribution tended to be lower in the treated group but this did not reach statistical significance (p = 0,09).

In conclusion, treatment with L-Carnosine improves metabolic control and reduces proteinuria in BTBR ob/ob mice, structurally mirrored by reduced renal hypertrophy. Our results thus indicate L-Carnosine as potential novel therapeutic to prevent or retard ESRF in type 2 diabetic patients..