Knockout mouse models of insulin signaling: Relevance past and future

Core Tip

Core tip: Insulin resistance is central to the pathophysiology of type 2 diabetes. The molecular origins of insulin resistance have been investigated using genetically modified mice. Much has been learned from this work, but new treatments for insulin resistance have not been forthcoming. Knockout mouse models of diabetes are limited by several factors including species differences in glucose metabolism. These are due partly to species differences in physiology, and partly to the failure of genetic modifications to produce an accurate model. Advancement may require a redirection of research efforts toward methods that are more directly relevant to human physiology.