Novel Dual-Acting Peroxisome Proliferator-Activated Receptor Alpha and Gamma Agonists
674-680
Correspondence
Dr. Rashmi Sharma, R/O 216-A, Last-Morh Gandhi-Nagar, Near Govt Flats, Jammu (Tawi) J&K (India), Pin 180004. Email: rashmichams@yahoo.com, drrashmi@india.com
Peroxisome proliferator-activated receptors (PPARs) are nuclear transcription factors, and play a central role in insulin sensitivity, lipid metabolism, and inflammation. PPAR -γ appears to improve glycaemic control by increasing peripheral insulin sensitivity and reducing hepatic glucose production, thereby helping to preserve beta-cell function. However, they have modest beneficial effects on lipid parameters. It has been observed that fibrate drugs which activate PPAR- α, produce significant improvements in dyslipidaemia and decrease atherosclerotic lesions, but do not affect glycaemia. Theoretically, a compound targeting both the α and γ PPARs simultaneously, might combine the benefits of thiazolidinediones (TZDs) and fibrates. Hence, there is a resurgence of interest in the development of new antidiabetic drugs that combine the insulin-sensitizing effects of PPARγ activation with the additional lipid-modifying activity of the other PPAR subtypes. Muraglitazar, Tesaglitazar, Ragaglitazar, Isohumulone, Farglitazar, and Naveglitazar are on the deck in late-stage clinical trials, and may be effective in reducing cardiovascular risk, but their long-term clinical effects are still unknown. The ongoing basic studies have elucidated the cardio protective role of PPAR delta. Therefore, further studies are on the track to develop PPA α/δ and PPARγ/ δ dual agonists and PPAR α/γ/δ pan agonists for the treatment of diabetic cardiovascular complications