Dialogue entre les voies de signalisation de l’insuline et les voies de prolifération cellulaire

Abstract

Epidemiological studies provide evidence for a close relationship between diabetes and cancer. Insulin is in fact a growth factor, and its binding to its membrane receptor activates intracellular signaling pathways involved in the regulation of both metabolism and cell proliferation. The balance between mitogenic and metabolic actions of insulin can be modulated by various mechanisms, including the way the ligand binds to its receptor or to the closely related insulin-like growth factor-1 (IGF-1) receptor. Cross-talks with other signaling pathways implicated in cell proliferation have also been described, like the Wnt/β catenin pathway, and involve the activation of common downstream effectors such as insulin receptor substrate-1 (IRS-1). Finally, the identification of new proteins activated by insulin and involved in intracellular signaling would allow a better understanding of the complex connections linking metabolic and proliferative regulatory pathways. As an example, the molecular adaptor Grb14, which is a specific inhibitor of insulin receptor catalytic activity, also controls insulin-induced metabolic and mitogenic signaling pathways through post-receptor mechanisms that remain to be fully elucidated.