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KMID : 1199120080320010021
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Korean Diabetes Journal
2008 Volume.32 No. 1 p.21 ~ p.29
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The Effect of α-Lipoic Acid on Proteinuria and Renal TGFβ Expression in Obese Type 2 Diabetic Rat Model
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Kang Seok-Woo
Lee Seong-Jin
Kim Dong-Sun
Kim Tae-Wha
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Abstract
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Background: It is well known that renal TGFβ 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 TGFβ 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 TGFβ protein expression at 35
weeks of age was measured by Western blot and represented by relative unit (RU). Immunohistochemical
staining for TGFβ 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 TGFβ
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 TGFβ 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 TGFβ 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). TGFβ 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 TGFβ protein expression in obese type 2 diabetic rat model. The
effect of ALA on diabetic nephropathy presented as proteinuria and renal TGFβ expression in diabetic
patients needs to be further clarified.
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KEYWORD
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Diabetes, Transforming growth factor β, α-Lipoic acid
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