Abstract
The members of the Suppressor of Cytokine Signaling (SOCS) protein family mainly modulate the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway. SOCS-1 and SOCS-3 have already been shown to influence growth and apoptosis of pancreatic beta cells. We hypothesized that SOCS-2, which is expressed in pancreatic islets, also contributes to β-cell physiology. We tested this hypothesis in vivo in SOCS-2-/- knockout mice and in vitro in Ins-1E rat insulinoma cells. We found that SOCS-2-/- mice have normal islet insulin secretion and unchanged glucose and insulin tolerance compared to wildtype controls. SOCS-2-/- are bigger than wildtype mice but body weight-corrected β-cell mass and islet morphology were normal. Growth hormone-induced proliferation of Ins-1E cells was not affected by either siRNA-mediated SOCS-2 knockdown or stable SOCS-2 overexpression. Interleukin-1β mediated cell death in vitro was unchanged after SOCS-2 knockdown. Similarly, autoimmune destruction of beta cells in vivo after multiple low-dose injections of streptozotocin (STZ) was not altered in SOCS-2-/- mice. In summary, SOCS-2-/- knockout mice have a normal function of insulin-producing pancreatic β-cells, a fully adapted beta cell mass and a normal morphology of the endocrine islets. Based on in vitro evidence, the increased β-cell mass in the mutants is likely due to indirect adaptive mechanisms and not the result of altered growth hormone signaling within the β-cells. Immune mediated β-cell destruction is also not affected by SOCS-2 ablation in vitro and in vivo.