HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) Online-Only Appendix All Versions of this Article: db06-1134v1 56/8/2036    most recent Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Cha, D.R. Articles by Guan, Y. Search for Related Content PubMed PubMed Citation Articles by Cha, D.R. Articles by Guan, Y. Social Bookmarking                What's this?

PPAR / dual agonist tesaglitazar attenuates diabetic nephropathy in db/db mice

¹Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA
² Peking University Diabetes Center, Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing 100083

Correspondence: youfei.guan{at}vanderbilt.edu

Peroxisome proliferator-activated receptors (PPARs) are nuclear transcription factors and play a central role in insulin sensitivity, lipid metabolism, and inflammation. Both PPAR and PPAR are expressed in the kidney and their agonists exhibit renoprotective effects in type 2 diabetes. In the present studies we investigated the effect of PPAR/ 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 HOMA-IR 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 TGFß1 expression in renal tissues of db/db mice. In cultured mesangial cells and proximal tubule cells where both PPAR and PPAR were expressed, tesaglitazar treatment abolished high glucose-induced total collagen protein production and type I and IV collagen gene expression. Collectively, tesaglitazar treatment 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/ agonists in treating type 2 diabetes and diabetic nephropathy.

CiteULike

Del.icio.us

Digg

Reddit

Technorati