The thiazolidinediones are a new class of antidiabetic agents that relieve the insulin resistance that arises in individuals with type 2 diabetes. These drugs are ligands for a nuclear receptor termed PPARgamma. The molecular mechanism whereby PPARgamma activation leads to insulin sensitization is unclear. In addition, thiazolidinediones also promote adipogenesis that could lead to a potential side effect of weight gain problem from patients treated with these drugs. This proposed work is to develop tissue-specific, constitutively active form of PPAR gamma in order to study this relationship in vivo. This work should lead to a better understanding of the etiology of type 2 diabetes and adipogenesis as well as a rationale for the use of PPAR gamma as a target for the development of more potent antidiabetic drugs.
