Underscoring the hepatocyte IR’s role (as opposed to the hepatic endothelial cell (EC) IRs) for liver insulin clearance, hepatocyte-specific expression of a dominant-negative carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1), which is necessary for liver cell IR and insulin internalization, inhibits insulin clearance, provoking hyperinsulinemia and metabolic insulin resistance [2]. Here, INS is linked to hyperinsulinism.