Ken-ichi Morishita and Hiroki Kakuta Pages 696 - 707 ( 12 )
Peroxisome proliferator-activated receptor gamma (PPARγ) is a ligand-dependent transcription factor that plays an important role in regulating glucose metabolism. Agonists of PPARγ, such as thiazolidinediones, have anti-hyperglycemic activity, and are therefore used to treat type 2 diabetes. However, the functional activity of PPARγ is manifested by heterodimers of PPARγ with retinoid X receptors (RXRs). Since RXR/PPARγ heterodimers can be activated not only by PPARγ agonists, but also by RXR agonists, RXR agonists are also attractive candidates for treatment of type 2 diabetes. However, RXR full agonists have side effects, such as triglyceride elevation and hypothyroidism. Therefore, RXR partial agonists have been developed as new anti-type 2 diabetes agent candidates with reduced side effects. In addition, RXR antagonists also show therapeutic potency in type 2 diabetes patients. Here, we review RXR full agonists, RXR antagonists, and RXR modulators (partial agonists) with reported anti-diabetic effects, and we discuss their potential suitability as anti-diabetic agents.
Retinoid X receptors, Agonists, Antagonists, Partial-agonists, Diabetes, Glucose-lowering effects.
Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 1–1–1 Tsushima-Naka, Kita-ku, Okayama 700– 8530