From bench to bedside: novel mechanisms and therapeutic advances through the development of selective peroxisome proliferator-activated receptor gamma modulators.

Type 2 diabetes is a complex disease that requires long-term therapy aimed at multiple targets. At Experimental Biology 2009 (www.eb2009.org), held last April in New Orleans, LA, the American Society for Nutrition hosted the symposium "From bench to bedside: novel therapeutic advances through the development of selective peroxisome proliferator-activated receptor gamma (PPARgamma) modulators." Presenters addressed the latest science on novel pathways that regulate metabolism and insulin resistance, including fibroblast growth factor 21 (FGF21) and adiponectin, as well as advances in our understanding of the biology of PPARgamma, including modes of action and recently discovered side effects of PPARgamma agonists. They also explored the pharmacologic and physiologic actions of FGF21 and adiponectin, metabolic regulators that could provide novel therapeutic opportunities in the future, as well as current data on selective PPARgamma modulators. These molecules offer a new direction in the search for more specific PPARgamma activators that will retain efficacy for the treatment of diabetes without major side effects.