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A Novel Partial PPAR alpha/gamma Dual Agonist SN159 Improves Insulin Sensitivity

Authors
Jung, YujungCao, YongkaiPaudel, SureshKim, Ki HyunYoon, GooCheon, Seung HoonLee, Jee-YoungKim, Su-NamKim, Yong Kee
Issue Date
Feb-2016
Publisher
대한화학회
Keywords
(E)-1-(3-Aminophenyl)-3-(5-bromo-4-hydroxy-2-methoxyphenyl)prop-2-en-1-o ne; SN159; PPAR alpha/gamma agonist; Insulin sensitivity
Citation
Bulletin of the Korean Chemical Society, v.37, no.2, pp 226 - 233
Pages
8
Journal Title
Bulletin of the Korean Chemical Society
Volume
37
Number
2
Start Page
226
End Page
233
URI
https://scholarworks.sookmyung.ac.kr/handle/2020.sw.sookmyung/9934
DOI
10.1002/bkcs.10662
ISSN
0253-2964
1229-5949
Abstract
We here demonstrate that (E)-1-(3-aminophenyl)-3-(5-bromo-4-hydroxy-2-methoxyphenyl)prop-2-en-1-one (SN159) is a novel peroxisome proliferator-activated receptor (PPAR) partial agonist that improves insulin sensitivity. SN159 interacted directly with PPAR alpha and PPAR gamma, which were confirmed by LanthaScreen ligand binding assay and molecular docking study. SN159 treatment leads to a significant improvement of insulin sensitivity, resulting in enhancing glucose uptake in muscle cells. SN159 stimulated adipogenic differentiation of 3T3-L1 preadipocytes, however, the effects were much weaker than those of PPAR gamma agonist troglitazone. In parallel, SN159 increased weakly the transcriptional activities of PPAR alpha/gamma, compared to the positive control. Furthermore, PPAR gamma activation and adipogenic differentiation by troglitazone were significantly reduced by treatment with SN159, indicating that SN159 is a partial agonist of PPARs. SN159 was able to enhance fatty acid oxidation and glucose utilization through the dual activation of PPAR alpha/gamma. Taken together, these results suggest that SN159 is a novel PPAR partial agonist, which can be used as potential therapeutic agents against type 2 diabetes and related metabolic disorders by enhancing glucose and lipid metabolism.
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