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Peroxisome proliferator-activated receptor alpha/gamma dual agonist tesaglitazar attenuates diabetic nephropathy in db/db mice
Cha, Dae Ryong; Zhang, Xiaoyan; Zhang, Yahua; Wu, Jing; Su, Dongming; Han, Jee Young; Fang, Xuefen; Yu, Bo; Breyer, Matthew D.; Guan, Youfei
刊名DIABETES
2007-08-01
DOI10.2337/db06-1134
56期:8页:2036-2045
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Endocrinology & Metabolism
研究领域[WOS]Endocrinology & Metabolism
关键词[WOS]IMPROVES INSULIN SENSITIVITY ; PPAR-ALPHA ; GAMMA AGONIST ; METABOLIC ABNORMALITIES ; NUCLEAR RECEPTORS ; LIPID-METABOLISM ; BODY-WEIGHT ; IN-VITRO ; RESISTANCE ; RATS
英文摘要

Peroxisome proliferator-activated receptors (PPARs) are nuclear transcription factors and play a central role in insulin sensitivity, lipid metabolism, and inflammation. Both PPAR alpha and -gamma are expressed in the kidney, and their agonists exhibit renoprotective effects in type 2 diabetes. In the present studies, we investigated the effect of the PPAR alpha/gamma dual agonist tesaglitazar on diabetic nephropathy in type 2 diabetic db/db mice. Treatment of db/db mice with tesaglitazar for 3 months significantly lowered fasting plasma glucose and homeostasis model assessment of insulin resistance levels but had little effect on body weight, adiposity, or cardiac function. Treatment with tesaglitazar was associated with reduced plasma insulin and total triglyceride levels and increased plasma adiponectin levels. Notably, tesaglitazar markedly attenuated albuminuria and significantly lowered glomerulofibrosis, collagen deposition, and transforming growth factor-beta 1 expression in renal tissues of db/db mice. In cultured mesangial cells and proximal tubule cells, where both PPAR alpha and -gamma were expressed, tesaglitazar treatment abolished high glucose- induced total collagen protein production and type I and IV collagen gene expression. Collectively, tesaglitazar treat ment not only improved insulin resistance, glycemic control, and lipid profile but also markedly attenuated albuminuria and renal glomerular fibrosis in db/db mice. These findings support the utility of dual PPAR alpha/gamma agonists in treating type 2 diabetes and diabetic nephropathy.

语种英语
WOS记录号WOS:000248473100010
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被引频次:47[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/54972
专题基础医学院_北京大学糖尿病中心
作者单位1.Vanderbilt Univ, Med Ctr, Dept Med, Div Nephrol & Hypertens, Nashville, TN USA
2.Peking Univ, Ctr Diabet, Dept Physiol & Pathophysiol, Hlth Sci Ctr, Beijing 100871, Peoples R China
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GB/T 7714
Cha, Dae Ryong,Zhang, Xiaoyan,Zhang, Yahua,et al. Peroxisome proliferator-activated receptor alpha/gamma dual agonist tesaglitazar attenuates diabetic nephropathy in db/db mice[J]. DIABETES,2007,56(8):2036-2045.
APA Cha, Dae Ryong.,Zhang, Xiaoyan.,Zhang, Yahua.,Wu, Jing.,Su, Dongming.,...&Guan, Youfei.(2007).Peroxisome proliferator-activated receptor alpha/gamma dual agonist tesaglitazar attenuates diabetic nephropathy in db/db mice.DIABETES,56(8),2036-2045.
MLA Cha, Dae Ryong,et al."Peroxisome proliferator-activated receptor alpha/gamma dual agonist tesaglitazar attenuates diabetic nephropathy in db/db mice".DIABETES 56.8(2007):2036-2045.
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