Abstract |
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.
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Authors | Hiroki Kakuta, Fuminori Ohsawa, Shoya Yamada, Makoto Makishima, Akihiro Tai, Hiroyuki Yasui, Yutaka Yoshikawa |
Journal | Biological & pharmaceutical bulletin
(Biol Pharm Bull)
Vol. 35
Issue 4
Pg. 629-33
( 2012)
ISSN: 1347-5215 [Electronic] Japan |
PMID | 22466572
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Blood Glucose
- Hypoglycemic Agents
- Liver X Receptors
- Orphan Nuclear Receptors
- PPAR gamma
- Retinoid X Receptors
- Triglycerides
- Cholesterol
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Topics |
- Animals
- Blood Glucose
(analysis)
- COS Cells
- Chlorocebus aethiops
- Cholesterol
(blood)
- Diabetes Mellitus, Type 2
(blood, drug therapy, pathology)
- Disease Models, Animal
- Hypoglycemic Agents
(therapeutic use)
- Liver
(pathology)
- Liver X Receptors
- Male
- Mice
- Organ Size
- Orphan Nuclear Receptors
(metabolism)
- PPAR gamma
(metabolism)
- Retinoid X Receptors
(agonists, metabolism)
- Triglycerides
(blood)
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