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Review
. 2004 Jun;25(6):331-6.
doi: 10.1016/j.tips.2004.03.012.

Peroxisome Proliferator-Activated Receptor Gamma in Diabetes and Metabolism

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Review

Peroxisome Proliferator-Activated Receptor Gamma in Diabetes and Metabolism

Shamina M Rangwala et al. Trends Pharmacol Sci. .

Abstract

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.

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