Journal
DIABETES
Volume 54, Issue 8, Pages 2460-2470Publisher
AMER DIABETES ASSOC
DOI: 10.2337/diabetes.54.8.2460
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Peroxisome proliferator-activated receptors (PPA-Rs) play key roles in the regulation of energy homeostasis and inflammation, and agonists of PPAR alpha and -gamma are. currently used therapeutically. Fibrates, first used in the 1970s for their lipid-modifying properties, were later shown to activate PPARa. These agents lower plasma triglycerides and VLDL particles and increase HDL cholesterol, effects that are associated with cardiovascular benefit. Thiazolidinediones, acting via PPAR gamma, influence free fatty acid flux and thus reduce insulin resistance and blood glucose levels. PPAR gamma agonists are therefore used to treat type 2 diabetes. PPAR alpha and -gamma agonists also affect inflammation, vascular function, and vascular remodeling. As knowledge of the pleiotropic effects of these agents advances, further potential indications are being revealed, including roles in the management of cardiovascular disease (CVD) and the metabolic syndrome. Dual PPAR alpha/gamma agonists (currently in development) look set to combine the properties of thiazolidinediones and fibrates, and they hold considerable promise for improving the management of type 2 diabetes and providing an effective therapeutic option for treating the multifactorial components of CVD and the metabolic syndrome. The functions of a third PPAR isoform, PPAR delta, and its potential as a therapeutic target are currently under investigation.
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