A Role for IR-β in the Free Fatty Acid Mediated Development of Hepatic Insulin Resistance?

Several studies have been conducted to elucidate the role of free fatty acids (FFAs) in the pathogenesis of type 2 diabetes, but the exact molecular mechanism by which FFAs alter glucose metabolism in the liver is still not completely understood.1-4 In a recent publication, Ragheb and co-workers have examined the effect of free fatty acid (FFA) treatment on insulin signaling and insulin resistance by using immunoprecipitation and immunoblotting to study the effect of high concentrations of insulin and FFAs on insulin receptor-beta (IR-β) and downstream elements in the PI3K pathway using the fructose-fed hamster model.5 Their results clearly show that free fatty acids have an insignificant effect on IR-β and supports previous findings that FFAs lead to insulin resistance in the liver via the PKC-NF B pathway.2,3