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The British Journal of Diabetes & Vascular Disease
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Thiazolidinedione-induced effects beyond glycaemic control

Ulf Smith

Department of Internal Medicine, The Sahlgrenska Academy, S-413 45 Göteborg, Sweden, ulf.smith{at}medic.gu.se

The thiazolidinediones exert their insulin sensitising effect by binding to the nuclear receptors (transcription factors) peroxisome proliferator activated receptor (PPAR) {gamma} and, to varying degrees, to PPAR{alpha}. Several different genes are activated by thiazolidinediones, many of which contribute to the increase in insulin sensitivity (eg. an increase in glucose uptake and utilisation, a decrease in gluconeogenesis and in insulin-antagonistic cytokines, such as tumour necrosis factor {alpha}). Activation of other genes indirectly reduces insulin resistance by, for example, increasing free fatty acid (FFA) uptake and oxidation resulting in lower circulating FFA levels. The action of thiazolidinediones at PPAR{gamma} is generally responsible for their insulin sensitising effects while action at PPAR{alpha} contributes to their lipid lowering effects. Therefore, the relative affinities of the different thiazolidinediones for PPAR{gamma} and PPAR{alpha} will also lead to a different spectrum of actions for each agent.

Key Words: diabetic dyslipidaemia • insulin resistance • PPAR receptors • pioglitazone • thiazolidinedione.

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The British Journal of Diabetes & Vascular Disease, Vol. 2, No. 1 suppl, S24-S27 (2002)
DOI: 10.1177/14746514020020010601
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This Article
Right arrow Abstract Freely available
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Right arrow Citing Articles via Google Scholar
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Right arrow Articles by Smith, U.
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Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?