Targeting PPARβ/δ for the treatment of type 2 diabetes mellitus.

INTRODUCTION: The nuclear receptors Peroxisome Proliferator-Activated Receptors (PPAR)α and PPARγ are therapeutic targets for hypertriglyceridemia and insulin resistance, respectively. Evidence is now emerging that the PPARβ/δ isotype is a potential pharmacological target for the treatment of insulin resistance and type 2 diabetes mellitus. AREAS COVERED: In this review, the capacity of PPARβ/δ to prevent the development of insulin resistance and type 2 diabetes mellitus is discussed. Special emphasis is placed on preclinical studies and the molecular mechanisms responsible for its actions in the main cell types involved in these pathologies: adipocytes, β-cells, skeletal muscle cells and hepatocytes. EXPERT OPINION: While several concerns remain for the development of PPARβ/δ agonists, these drugs have demonstrated their efficacy in the treatment of insulin resistance and type 2 diabetes mellitus in preclinical studies, as well as in a few short clinical studies in humans. Although this data is promising, additional studies must be performed to confirm the efficacy and safety of these drugs in the treatment of type 2 diabetes mellitus.