Mouse models have been more widely used to study the roles of Rho GEFs than Rho GTPases, and this approach has shown that Rho GEFs are important regulators of glucose homeostasis in vivo, with deficiencies or deregulated expression commonly resulting in impaired insulin signaling, insulin resistance, glucose intolerance, and the development of metabolic syndrome and type 2 diabetes. This evidence concerns the gene INS and Insulin resistance.