A new study has demonstrated that serpinB1, a liver-derived protease inhibitor, can promote β-cell proliferation in mice, zebrafish and humans. The researchers found that mice lacking serpinB1 had reduced β-cell compensation in response to insulin resistance. Furthermore, treating islets with serpinB1 in vitro resulted in inhibition of elastase and activation of growth factor and survival-factor signalling pathways. Although these findings are an important step in achieving regeneration of functional β cells, more work is needed to identify other factors involved and to determine whether this approach can be used safely in humans.