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学科主题: 基础医学
题名:
PPAR alpha agonist fenofibrate improves diabetic nephropathy in db/db mice
作者: Park, CW1; Zhang, Y1; Zhang, X1; Wu, J1; Chen, L1; Cha, DR1; Su, D1; Hwang, MT1; Fan, X1; Davis, L1; Striker, G1; Zheng, F1; Breyer, M1; Guan, Y1
关键词: pPAR alpha ; type II diabetes ; diabetic nephropathy ; fenofibrate
刊名: KIDNEY INTERNATIONAL
发表日期: 2006-05-01
DOI: 10.1038/sj.ki.5000209
卷: 69, 期:9, 页:1511-1517
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Urology & Nephrology
研究领域[WOS]: Urology & Nephrology
关键词[WOS]: ACTIVATED RECEPTOR-GAMMA ; INSULIN-RESISTANCE ; CARDIOVASCULAR-DISEASE ; RENAL INJURY ; RATS ; EXPRESSION ; GLOMERULOSCLEROSIS ; ROSIGLITAZONE ; COMPLICATIONS ; TRIGLYCERIDES
英文摘要:

Peroxisome proliferator-activated receptor alpha (PPAR alpha) is a member of the ligand-activated nuclear receptor superfamily, and plays an important role in lipid metabolism and glucose homeostasis. The purpose of this study is to determine whether the activation of PPAR alpha by fenofbrate would improve diabetes and its renal complications in type II diabetes mellitus. Male C57 BLKS db/db mice and db/m controls at 8 weeks of age were divided to receive either a regular diet chow (db/db, n = 8; db/m, n = 6) or a diet containing fenofibrate (db/db, n = 8; db/m, n = 7). Mice were followed for 8 weeks. Fenofibrate treatment dramatically reduced fasting blood glucose (P < 0.001) and HbA1c levels (P < 0.001), and was associated with decreased food intake (P < 0.01) and slightly reduced body weight. Fenofibrate also ameliorated insulin resistance (P < 0.001) and reduced plasma insulin levels (P < 0.05) in db/db mice. Hypertrophy of pancreatic islets was decreased and insulin content markedly increased (P < 0.05) in fenofibrate-treated diabetic animals. In addition, fenofibrate treatment significantly reduced urinary albumin excretion (P < 0.001). This was accompanied by dramatically reduced glomerular hypertrophy and mesangial matrix expansion. Furthermore, the addition of fenofibrate to cultured mesangial cells, which possess functional active PPAR alpha, decreased type I collagen production. Taken together, the PPAR alpha agonist fenofibrate dramatically improves hyperglycemia, insulin resistance, albuminuria, and glomerular lesions in db/db mice. The activation of PPAR alpha by fenofibrate in mesangial cells may partially contribute to its renal protection. Thus, fenofibrate may serve as a therapeutic agent for type II diabetes and diabetic nephropathy.

语种: 英语
WOS记录号: WOS:000237238400010
Citation statistics:
内容类型: 期刊论文
版本: 出版稿
URI标识: http://ir.bjmu.edu.cn/handle/400002259/51632
Appears in Collections:基础医学院_生理学与病理生理学系_期刊论文

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作者单位: 1.Mt Sinai Sch Med, Dept Med & Geriatr, New York, NY USA
2.Vanderbilt Univ, Med Ctr, Dept Med, Div Nephrol, Nashville, TN 37232 USA
3.Vanderbilt Univ, Med Ctr, Div Nephrol & Hypertens, Nashville, TN 37232 USA
4.Peking Univ, Hlth Sci Ctr, Dept Physiol, Beijing 100871, Peoples R China

Recommended Citation:
Park, CW,Zhang, Y,Zhang, X,et al. PPAR alpha agonist fenofibrate improves diabetic nephropathy in db/db mice[J]. KIDNEY INTERNATIONAL,2006,69(9):1511-1517.
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