PPAR gamma and the treatment of insulin resistance

Numerous studies across several population groups hale indicated that insul in resistance plays a central role in the development of type 2 diabetes me llitus (T2DM). Moreover; this disorder is also strongly associated with oth er metabolic syndromes, including hypertension dyslipidemias and polycystic ovarian syndrome (PCOS). Recent advances have demonstrated that pharmacolo gical agents of the thiazolidinedione class can reverse insulin resistance and profoundly improve many of these associated symptoms. These effects hav e been documented in a variety of genetic and acquired animal models of ins ulin resistance, as well as in numerous clinical trials in patients with in sulin resistance. These compounds appear to enhance insulin action by modul ating the activity of the nuclear receptor peroxisome proliferator-activate d receptor (PPAR)gamma. This activation results in changes in the expressio n of a number of genes that are critically involved in glucose and lipid me tabolism, as well as in insulin signal transduction. While precise events t hat occur downstream from PPAR gamma modulation remain-uncertain new insigh ts are emerging from knockout studies in mice al rd the identification of g enetic variants in humans. These findings indicate that there is still much to learn about the molecular biology and physiology of these interesting r eceptors, and that research in this area can lead to more effective and saf er drugs to treat insulin resistance and associated syndromes.