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

Expert Opin Ther Targets. 2012 Feb;16(2):209-23. doi: 10.1517/14728222.2012.658370. Epub 2012 Jan 27.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adipocytes / metabolism
  • Animals
  • B-Lymphocytes / metabolism
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / metabolism
  • Hepatocytes / metabolism
  • Humans
  • Ligands
  • Muscle Fibers, Skeletal / metabolism
  • PPAR delta / agonists*
  • PPAR delta / metabolism
  • PPAR-beta / agonists*
  • PPAR-beta / metabolism

Substances

  • Ligands
  • PPAR delta
  • PPAR-beta