Abstract: FR-PO602

Renoprotective Effects of Aliskiren in a Non-Obese Type 2 Diabetic Model Rat

Session Information

Category: Diabetes

  • 501 Diabetes Mellitus and Obesity: Basic - Experimental

Authors

  • Watanabe, Kentaro, Kobe University Graduate School of Medicine, Kobe, Japan
  • Fujii, Hideki, Kobe University Graduate School of Medicine, Kobe, Japan
  • Nakai, Kentaro, Kobe University Graduate School of Medicine, Kobe, Japan
  • Watanabe, Shuhei, Kobe University Graduate School of Medicine, Kobe, Japan
  • Kono, Keiji, Kobe University Graduate School of Medicine, Kobe, Japan
  • Goto, Shunsuke, Kobe University Graduate School of Medicine, Kobe, Japan
  • Shinohara, Masami, CLEA Japan, Inc., Meguro, Japan
  • Nishi, Shinichi, Kobe University Graduate School of Medicine, Kobe, Japan
Background

Previous experimental and clinical studies showed that various factors such as oxidative stress and renin-angiotensin system (RAS) were involved in pathogenesis of diabetic nephropathy (DN), and Aliskiren (ALS), which is a direct renin inhibitor, was useful for prevention of DN progression. However, there are no studies using non-obese type 2 diabetic animal models. The aim of our study was to elucidate the effects of ALS on DN in a non-obese type 2 diabetic rat model.

Methods

We used male Sprague-Dawley (SD) rats and Spontaneously Diabetic Torii (SDT) rats, which are known as non-obese type 2 diabetic animal models, in the present study. At 20 weeks of age, SD rats were assigned to the control group (SD group) and SDT rats were randomly divided into two groups: placebo-treated group (DM group) and ALS-treated group (ALS group). ALS was administered to the rats in the ALS group for 10 weeks. At 30 weeks of age, these rats were killed and then urinary and blood biochemical analyses and renal mRNA expression analysis were performed in all the groups.

Results

Despite similar blood pressure and renal function, urinary excretion of albumin was significantly lower in the ALS than in the DM group. Urinary excretion of angiotensinogen and 8-hydroxydeoxyguanosine (8-OHdG) were also significantly lower in the ALS compared to the DM group. Serum transforming growth factor-β (TGF-β) levels tended to be lower in the ALS than in the DM group. Renal mRNA expressions of angiotensin II type 1 receptor, nicotinamide adenine dinucleotide phosphate oxidase, and TGF-β were significantly suppressed in the ALS compared to the DM group. Furthermore, renal nephrin mRNA expression was ameliorated by ALS treatment. Urinary excretion of albumin was positively and significantly correlated with urinary excretion of 8-OHdG as well as serum levels and renal mRNA expression of TGF-β.

Conclusion

The results of present study suggested that ALS provided renoprotective effects through RAS inhibition and reduction of oxidative stress and TGF-β even in a non-obese type 2 diabetic model rat.