Peroxisome proliferator-activated receptor gamma in diabetes and metabolism

Trends Pharmacol Sci. 2004 Jun;25(6):331-6. doi: 10.1016/


The peroxisome proliferator-activated receptor gamma (PPAR-gamma) has been the focus of intense research during the past decade because ligands for this receptor have emerged as potent insulin sensitizers used in the treatment of type 2 diabetes. Recent advances include the discovery of novel genes that are regulated by PPAR-gamma, which helps explain how activation of this adipocyte-predominant transcription factor regulates glucose and lipid homeostasis. Increased levels of circulating free fatty acids and lipid accumulation in non-adipose tissue have been implicated in the development of insulin resistance. This situation is improved by PPAR-gamma ligands, which promote fatty acid storage in fat depots and regulate the expression of adipocyte-secreted hormones that impact on glucose homeostasis. The net result of the pleiotropic effects of PPAR-gamma ligands is improvement of insulin sensitivity, although undesired side-effects limit the utility of this therapy. It might be possible to dissociate the anti-diabetic and adverse effects through selective modulation of PPAR-gamma activity.

Publication types

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

MeSH terms

  • Adipocytes / physiology
  • Adipose Tissue / physiology
  • Animals
  • Diabetes Mellitus / metabolism*
  • Diabetes Mellitus / physiopathology*
  • Humans
  • Insulin Resistance / physiology
  • Ligands
  • Receptors, Cytoplasmic and Nuclear / metabolism
  • Receptors, Cytoplasmic and Nuclear / physiology*
  • Transcription Factors / metabolism
  • Transcription Factors / physiology*


  • Ligands
  • Receptors, Cytoplasmic and Nuclear
  • Transcription Factors