The redundant role of JAK2 in regulating pancreatic β-cell mass.

Janus kinase (JAK) 2 is a non-receptor tyrosine kinase that mediates the downstream effects of various growth factors, including growth hormone,1 prolactin,2 placental lactogen3 and erythropoietin (EPO).4 EPO is a hematopoietic growth factor that is largely known for its role in promoting proliferation, differentiation and survival of cells in the erythroid lineage. Global loss of the EPO receptor (EPO-R) has been shown to be embryonically lethal in mice due to anemia attributed to defects in erythropoiesis.5 Interestingly, mice with global deficiency of JAK2 share a similar developmental phenotype as the EPO-R knockout mice,6 demonstrating that JAK2 is essential in eliciting the biological effects of EPO, particularly in erythrocytosis. Recent studies from our group have shown that exogenous EPO protects mice against diabetes through direct effects on pancreatic β-cells, and these protective effects are dependent on the presence of JAK2 in the β-cells.7 Here, we briefly highlight the cytoprotective effects of exogenous EPO in the pancreatic β-cells, as well as our new findings on the redundant role of JAK2 in β-cell expansion after high-fat feeding in mice.