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Diabetes 53:S43-S50, 2004
© 2004 by the American Diabetes Association, Inc.

Section II: Nuclear Receptors and Islet Function

The Biology of Peroxisome Proliferator-Activated Receptors

Relationship With Lipid Metabolism and Insulin Sensitivity

Pascal Ferré

From INSERM Unit 465, Cordeliers Biomedical Research Center, Paris, France

Peroxisome proliferator-activated receptors (PPARs) are transcription factors belonging to the superfamily of nuclear receptors. Three isoforms ({alpha}, {delta}, and {gamma}) have been described. They act on DNA response elements as heterodimers with the nuclear retinoic acid receptor. Their natural activating ligands are fatty acids and lipid-derived substrates. PPAR-{alpha} is present in liver, heart, and, to a lesser extent, skeletal muscle. When activated, it promotes fatty acid oxidation, ketone body synthesis, and glucose sparing. Fibrates, which are used as hypolipidemic drugs, are ligands of PPAR-{alpha}. PPAR-{delta} is ubiquitous and could also favor fatty acid oxidation in tissues in which PPAR-{alpha} is absent or less expressed. PPAR-{gamma} is expressed in adipose tissue, lower intestine, and cells involved in immunity. Activation of PPAR-{gamma} induces the differentiation of preadipocytes into adipocytes and stimulates triglyceride storage. Thiazolidinediones are compounds used as hypoglycemic, muscle insulin-sensitizing agents in type 2 diabetes. Unexpectedly, they are activators of PPAR-{gamma}. Their action on muscle insulin sensitivity may be secondary to the lowering of circulating lipids on PPAR-{gamma} activation and to the secretion by adipocytes of insulin-sensitizing hormones such as adiponectin, all promoting glucose utilization. The PPARs are thus major regulators of lipid and glucose metabolism, allowing adaptation to the prevailing nutritional environment.

Address correspondence and reprint requests to Pascal Ferré, INSERM Unit 465, Centre de Recherches Biomédicales des Cordeliers, 15, rue de l’Ecole de Médecine, 75270 Paris Cedex 06, France. E-mail: pferre{at}bhdc.jussieu.fr


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Copyright © 2004 by the American Diabetes Association.