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PPARδ activation protects endothelial function in diabetic mice
Tian X.Y.2; Wong W.T.2; Wang N.4; Lu Y.2; Cheang W.S.2; Liu J.2; Liu L.2; Liu Y.1; Lee S.S.-T.2; Chen Z.Y.2; Cooke J.P.3; Yao X.2; Huang Y.2
2012-12-01
Source PublicationDiabetes
ISSN00121797 1939327X
Volume61Issue:12Pages:3285-3293
Abstract

Recent evidence highlights the therapeutic potential of peroxisome proliferator-activated receptor-δ (PPARδ) agonists to increase insulin sensitivity in diabetes. However, the role of PPARd in regulating vascular function is incompletely characterized. We investigate whether PPARδ activation improves endothelial function in diabetic and obese mice. PPARδ knockout (KO) and wild-type (WT) mice fed with high-fat diet and db/db mice were used as diabetic mouse models, compared with PPARδ KO and WT mice on normal diet and db/m mice. Endothelium-dependent relaxation (EDR) was measured by wire myograph. Flow-mediated vasodilatation (FMD) was measured by pressure myograph. Nitric oxide (NO) production was examined in primary endothelial cells from mouse aortae. PPARδ agonist GW1516 restored EDRs in mouse aortae under high-glucose conditions or in db/db mouse aortae ex vivo. After oral treatment with GW1516, EDRs in aortae and FMDs in mesenteric resistance arteries were improved in obese mice in a PPARδ-specific manner. The effects of GW1516 on endothelial function were mediated through phosphatidylinositol 3-kinase (PI3K) and Akt with a subsequent increase of endothelial nitric oxide synthase (eNOS) activity and NO production. The current study demonstrates an endothelial-protective effect of PPARδ agonists in diabetic mice through PI3K/Akt/eNOS signaling, suggesting the therapeutic potential of PPARδ agonists for diabetic vasculopathy. © 2012 by the American Diabetes Association.

DOI10.2337/db12-0117
URLView the original
Indexed BySCI
Language英语
WOS Research AreaEndocrinology & Metabolism
WOS SubjectEndocrinology & Metabolism
WOS IDWOS:000312041700036
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Cited Times [WOS]:38   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Affiliation1.Peking University Health Science Center
2.Chinese University of Hong Kong
3.Stanford University School of Medicine
4.Xi'an Jiaotong University
Recommended Citation
GB/T 7714
Tian X.Y.,Wong W.T.,Wang N.,et al. PPARδ activation protects endothelial function in diabetic mice[J]. Diabetes,2012,61(12):3285-3293.
APA Tian X.Y..,Wong W.T..,Wang N..,Lu Y..,Cheang W.S..,...&Huang Y..(2012).PPARδ activation protects endothelial function in diabetic mice.Diabetes,61(12),3285-3293.
MLA Tian X.Y.,et al."PPARδ activation protects endothelial function in diabetic mice".Diabetes 61.12(2012):3285-3293.
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