Antidiabetic actions of a non-agonist PPARγ ligand blocking Cdk5-mediated phosphorylation

Towards better antidiabetic drugs The nuclear receptor PPARγ is the target of thiazolidinedione antidiabetics including rosiglitazone and pioglitazone. These full PPARγ agonists are effective and well tolerated in most patients, but cause fluid retention and weight gain in a minority. In this proof-of-concept study, Choi et al . show the development of specific PPARγ ligands that retain antidiabetic activity through blockade of Cdk5-mediated PPARγ phosphorylation, but that are not full PPARγ agonists. In mouse models, these ligands do not cause the side effects sometimes associated with full PPARγ agonists.