Considering the importance of insulin clearance for the regulation of circulating insulin levels, it would be of interest to investigate how IDE levels and activity are impacted in mouse models with liver-specific deletion of, for example, IR, IRS1/2, PI3K and rictor, which could help to elucidate the mechanistic basis for the hyperinsulinemia occurring in these models (Table 3), and its impact on IDE levels and activity. Here, INS is linked to hyperinsulinism.