Peroxisome proliferator-activated receptor (PPAR) γ is a nuclear receptor that, when activated, regulates fatty acid storage and glucose metabolism. The best known class of PPARγ ligands are the thiazolidinediones, including troglitazone and rosiglitazone . GW 1929 is a non-thiazolidinedione activator of PPARγ that binds with a Ki value of 1.4 nM, with greater than 1,000-fold selectivity over other PPAR subtypes. It has anti-hyperglycemic and anti-hyperlipidemic activity when given orally in mouse and rat models of type 2 diabetes. Both in vitro and in vivo effects of GW 1929 on PPARγ greatly exceed those produced by troglitazone. In addition, GW 1929 has neuroprotective effects in global cerebral ischemic-reperfusion injury that are related to reduced inflammation and apoptotic DNA fragmentation.
