Diabetes and Suppressors of Cytokine Signaling Proteins

• CIS, cytokine-inducible SH2-containing protein
• IL, interleukin
• IFN, interferon
• IRS, insulin receptor substrate
• JAK, Janus kinase
• MAP, mitogen-activated protein
• NF-κB, nuclear factor-κB
• SOCS, suppressors of cytokine signaling
• STAT, signal transducers and activators of transcription
• TAK-1 kinase, transforming growth factor-β–activated kinase
• TNF, tumor necrosis factor

The pathogenesis of type 1 diabetes is not clearly understood, but it is generally accepted that type 1 diabetes is an immune-mediated disease caused by inflammation in the islets of Langerhans. Infiltrating macrophages release proinflammatory cytokines such as interleukin (IL)-1β and tumor necrosis factor (TNF)-α, which are toxic to the β-cell. Activated T-cells also produce proinflammatory cytokines such as TNF-α and interferon (IFN)-γ and express the apoptosis-inducing protein FasL. Moreover, CD8⁺ T-cells induce cell death via the perforin-granzyme pathway. The net effect of these different factors results in specific destruction of the insulin-producing β-cells (1). Type 2 diabetes occurs when β-cell secretory capacity fails to compensate for insulin resistance. In type 2 diabetes, cytokines are known to be involved in insulin and leptin resistance (2,3), and cytokines have also been suggested to contribute to β-cell failure of type 2 diabetes (4).

In this review we focus on a group of proteins, the suppressors of cytokine signaling (SOCS), which affect cytokine signaling and appear to play an important role in the pathological processes leading to both type 1 and type 2 diabetes.