2012年
Feasibility of structural modification of retinoid X receptor agonists to separate blood glucose-lowering action from adverse effects: studies in KKA(y) type 2 diabetes model mice
Biological & pharmaceutical bulletin
- 巻
- 35
- 号
- 4
- 開始ページ
- 629
- 終了ページ
- 633
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1248/bpb.35.629
- 出版者・発行元
- PHARMACEUTICAL SOC JAPAN
Retinoid X receptor (RXR) agonists are reported to exhibit blood glucose-lowering action owing to peroxisome proliferator-activated receptor (PPAR)/RXR or liver X receptor (LXR)/RXR activation, but may also cause adverse effects such as blood triglyceride elevation. In order to examine the feasibility of separating the glucose-lowering action from the adverse effects, we examined the effects of RXR agonists (NEt-TMN), NEt-3IB, and NEt-3IP, which have different heterodimer-activating patterns, in KKA(y) type 2 diabetes model mice. We found that NEt-3IB induced lower degrees of hepatomegaly and blood triglyceride (TG) elevation than the other RXR agonists, even though all of them showed similar blood glucose-lowering action on repeated administration. These findings indicate that structural modification of RXR agonists is a potentially effective strategy to reduce adverse effects while retaining desired activities.
- リンク情報
- ID情報
-
- DOI : 10.1248/bpb.35.629
- ISSN : 0918-6158
- ORCIDのPut Code : 51294777
- PubMed ID : 22466572
- Web of Science ID : WOS:000302200900028