Using several genetically modified mouse models of loss- and gain-of-function of Ceacam1, we have demonstrated that CEACAM1 plays a critical role in promoting hepatic insulin clearance, and that its loss in the liver causes chronic hyperinsulinemia followed by systemic insulin resistance, altered lipid homeostasis, hepatosteatosis, and visceral obesity (5–7). Here, INS is linked to hyperinsulinism.