Suppressor of cytokine signalling (SOCS) proteins as guardians of inflammatory responses critical for regulating insulin sensitivity

Abstract

Overactivation of immune pathways in obesity is an important cause of insulin resistance and thus new approaches aimed to limit inflammation or its consequences may be effective for treating Type 2 diabetes. The SOCS (suppressors of cytokine signalling) are a family of proteins that play an essential role in mediating inflammatory responses in both immune cells and metabolic organs such as the liver, adipose tissue and skeletal muscle. In the present review we discuss the role of SOCS1 and SOCS3 in controlling immune cells such as macrophages and T-cells and the impact this can have on systemic inflammation and insulin resistance. We also dissect the mechanisms by which SOCS (1-7) regulate insulin signalling in different tissues including their impact on the insulin receptor and insulin receptor substrates. Lastly, we discuss the important findings from SOCS whole-body and tissue-specific null mice, which implicate an important role for these proteins in controlling insulin action and glucose homoeostasis in obesity.