The Effect of alpha-Lipoic Acid on Proteinuria and Renal TGFbeta Expression in Obese Type 2 Diabetic Rat Model / 당뇨병

ABSTRACT

BACKGROUND: It is well known that renal TGFbeta expression is related to the development of diabetic nephropathy. Alpha-lipoic acid (ALA), a potent antioxidant and cofactor of mitochondrial respiratory enzymes, can improve the insulin resistance and the vascular endothelial dysfunction, and suppresses the development of diabetic vascular complications. This study was undertaken to investigate whether ALA could reduce urinary protein excretion and renal TGFbeta protein expression in obese type 2 diabetes mellitus animal model, Otsuka Long-Evans Tokushima Fatty (OLETF) rat. METHODS: Obese 30 male OLETF rats were randomly divided to 3 groups at the age of 30 weeks. The rats in the Control group fed normal rat chow while the rats in the ALA group were fed with rat chow containing ALA (0.5% of food weight). Ten rats in the Pair-fed group were fed with normal rat chow, but were given the same amount of food as consumed by the ALA group. During 5 weeks of ALA feeding, food intake and body weight were checked in metabolic chamber. Blood glucose levels, HbA1c and urinary protein excretion were measured at 30 weeks and 35 weeks of age, and renal TGFbeta protein expression at 35 weeks of age was measured by Western blot and represented by relative unit (RU). Immunohistochemical staining for TGFbeta protein in renal tissue was also examined at 35 weeks of age. RESULTS: Food intake, body weight, blood glucose levels, HbA1c and urinary protein excretion among the Control, ALA and Pair-fed groups at 30 weeks of age were not different. At 35 weeks of age, food intake was significantly decreased in the ALA group than the Control group (Control group vs. ALA group, 27.7 +/- 1.1 g/day vs. 22.4 +/- 1.4 g/day, P < 0.001), and body weight was significantly decreased in the ALA group than the Control and Pair-fed groups (Control group 694.4 +/- 10.3 g, ALA group 600.4 +/- 7.4 g, Pair-fed group 685.4 +/- 11.6 g, P < 0.001). Blood glucose levels were significantly decreased in the ALA group than the Control and Pair-fed groups (Control group 157.7 +/- 4.6 mg/dL, ALA group 130.7 +/- 4.8 mg/dL, Pair-fed group 153.7 +/- 3.3 mg/dL, P < 0.001) although blood glucose levels from 30 weeks to 34 weeks of age and HbA1c at 35 weeks of age were not different among the groups. Urinary protein excretion and renal TGFbeta protein expression were significantly decreased in the ALA group than the Control and Pair-fed groups (urinary protein excretion, Control group 5.033 +/- 0.254 mg/mgCr, ALA group 3.633 +/- 0.303 mg/mgCr, Pair-fed group 4.977 +/- 0.339 mg/mgCr, P < 0.001; renal TGFbeta protein expression, Control group 7.09 +/- 0.17 RU, ALA group 4.14 +/- 0.26 RU, Pair-fed group 7.00 +/- 0.29 RU, P < 0.001). In the ALA group at 35 weeks of age, urinary protein excretion and renal TGFbeta protein expression were positively related in the Control, ALA and Pair-fed groups (Control group, r = 0.847, P = 0.002; ALA group, r = 0.954, P < 0.001; Pair-fed group, r = 0.858, P = 0.002). TGFbeta staining in glomeruli was observed in all groups but was decreased in the ALA group at 35 weeks of age. CONCLUSION: These results suggest that ALA may prevent the increase of food intake, body weight, blood glucose, urinary protein excretion and renal TGFbeta protein expression in obese type 2 diabetic rat model. The effect of ALA on diabetic nephropathy presented as proteinuria and renal TGFbeta expression in diabetic patients needs to be further clarified.