These early observations in cell systems are bolstered by the manifestation of reduced insulin clearance followed by chronic hyperinsulinemia and its downregulatory effect on insulin receptors to cause hepatic insulin resistance in mice with null mutation or liver-specific Ceacam1 gene deletion, and in mice with liver-specific inactivation of CEACAM1 (reviewed in [1]). Here, INSR is linked to hyperinsulinism.