Journal
ENDOCRINE REVIEWS
Volume 25, Issue 6, Pages 899-918Publisher
ENDOCRINE SOC
DOI: 10.1210/er.2003-0036
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Funding
- NIDDK NIH HHS [1-P01-DK59820-01] Funding Source: Medline
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The peroxisome proliferator- activated receptor gamma ( PPAR gamma) is a prototypical member of the nuclear receptor superfamily and integrates the control of energy, lipid, and glucose homeostasis. PPAR gamma can bind a variety of small lipophilic compounds derived from metabolism and nutrition. These ligands, in turn, determine cofactor recruitment to PPAR gamma, regulating the transcription of genes in a variety of metabolic pathways. PPAR gamma is the main target of the thiazolidinedione class of insulin- sensitizing drugs, which are currently a mainstay of therapy for type 2 diabetes. However, this therapy has a number of side effects. Here, we review the clinical consequences of PPAR gamma polymorphisms in humans, as well as several studies in mice using general or tissue- specific knockout techniques. We also discuss the recent pharmacological literature describing a variety of new PPAR gamma partial agonists and antagonists, as well as pan- PPAR agonists. The results of these studies have added to the understanding of PPAR gamma function, allowing us to hypothesize a general mechanism of PPAR gamma action and speculate on future trends in the use of PPAR gamma as a target in the treatment of type II diabetes.
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