HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

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.

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.
AuthorsHiroki Kakuta, Fuminori Ohsawa, Shoya Yamada, Makoto Makishima, Akihiro Tai, Hiroyuki Yasui, Yutaka Yoshikawa
JournalBiological & pharmaceutical bulletin (Biol Pharm Bull) Vol. 35 Issue 4 Pg. 629-33 ( 2012) ISSN: 1347-5215 [Electronic] Japan
PMID22466572 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Blood Glucose
  • Hypoglycemic Agents
  • Liver X Receptors
  • Orphan Nuclear Receptors
  • PPAR gamma
  • Retinoid X Receptors
  • Triglycerides
  • Cholesterol
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)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: