Time End : 9 / 8 / 2008 3 : 15 : 00

Background and aims: We have proposed that development of insulin sensitizer therapies has been delayed because of focus on nuclear receptor activation. Further, superior pharmacological profiles, [e.g., less plasma volume expansion (and edema) as well as greater reductions in blood pressure and corrections of dyslipidemia] might be obtained by minimizing direct activation of nuclear receptors. These studies seek to establish whether a series of insulin sensitizers could be established that limit or avoid interaction with nuclear receptors. We also aim to directly benchmark a prototype “PPAR-sparing” compound against pioglitazone in the clinic.