Beneficial effects of thiazolidinediones on diabetic nephropathy in OLETF rats.
OBJECTIVE
Diabetic nephropathy is the most serious of complications in diabetes mellitus. Thiazolidinedione (TZD) is thought to ameliorate diabetic nephropathy; however, the mechanism underlying this effect has not been elucidated. We hypothesized that the vascular endothelial growth factor (VEGF) participates in the pathogenesis of diabetic nephropathy and that TZD may be beneficial for the treatment of diabetic nephropathy because of the effect it has on VEGF.


METHODS
23 Otsuka- Long-Evans-Tokushima-Fatty (OLETF) rats and eight control Long-Evans-Tokushima-Otsuka (LETO) rats were divided into the following four groups: LETO group, control OLETF group, pioglitazone treated group (10mg/ kg/day), and rosiglitazone treated group (3mg/kg/day).


RESULTS
A progressive increase in urinary protein excretion was observed in the diabetic rats. Glomerular VEGF expression in the control OLETF rats was significantly higher than in the control LETO rats. However, there was a significant reduction in both the glomerular VEGF expression and the VEGF mRNA levels after treatment with pioglitazone and rosiglitazone. The twenty-four hour urine protein levels were significantly decreased in both groups of the treated OLETF rats.


CONCLUSIONS
These results suggest that TZD may have beneficial effects on diabetic nephropathy by reducing the VEGF expression.
Lee
Mi Young
MY
Department of Internal Medicine, Yonsei University Wonju College of Medicine, 162 Ilsandong, Wonju, Gangwondo, Korea.
Lee
Eun Young
EY
Lee
Byung Jun
BJ
Won
Chan Sik
CS
Koh
Jang Hyun
JH
Shin
Jang Yel
JY
Shin
Young Goo
YG
Cho
Byung Pil
BP
Chung
Choon Hee
CH
D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D003928:Diabetic Nephropathies / Q000188:drug therapy*; D004195:Disease Models, Animal; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D008297:Male; D000077205:Pioglitazone; D051381:Rats; D020318:Rats, Long-Evans; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000627:therapeutic use*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D042461:Vascular Endothelial Growth Factor A; D000077154:Rosiglitazone; D000077205:Pioglitazone