Molecular basis of insulin resistance: the role of IRS and Foxo1 in the control of diabetes mellitus and its complications

Insulin/IGF-1 signaling plays a central role in control of cellular metabolism and survival, while insulin receptor substrate (IRS) protein-1 and -2 and downstream PI-3 kinase→Akt→Foxo1 signaling cascade play key roles in many functions of insulin/IGF-1. Dysregulation of this branch of signaling cascades may provide a mechanism for insulin resistance as we observed in cells, animals, and even humans. Targeting this branch of IRS→Foxo1 signaling may provide us with fundamental strategies for drug development in the future.