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

Abstract

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.

Keywords:

• fatty acids
• IL-6
• NF-κB
• PPARβ/δ
• STAT-3

Acknowledgements

The author's work that is summarized in this review was supported by grants from the Ministerio de Ciencia e Innovación of Spain (SAF2009-06939). CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM) is an Instituto de Salud Carlos III project. Laia Salvadó and Lucía Serrano-Marco were supported by grants from the Ministerio de Ciencia e Innovación of Spain. We thank the Language Advisory Service of the University of Barcelona for helpful assistance.

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