fig2

Figure 2. The double role of CEACAM1 in hepatocytes. In response to stimuli, insulin is released from pancreatic β-cells in pulses. This would stimulate CEACAM1 phosphorylation by the activated IR in hepatocytes. Phosphorylated CEACAM1 stabilizes the IR-insulin endocytosis complex and induces the rate of its uptake and insulin delivery to lysosomal degradation. By binding to FASN, expressed at high levels in the perinuclear region, CEACAM1 dissociates from the complex to allow the detachment of insulin from its receptor in the acidic environment of endosomes to undergo degradation. This also leads to suppression of FASN activity. In this manner, FASN activity in hepatocytes is kept at minimal under normal physiologic conditions despite its high levels resulting from increased transcription by the physiologic high insulin in the portal circulation. Thus, the pulsatility of secreted insulin and ensuing CEACAM1 phosphorylation by activated insulin receptors protect the liver against the otherwise lipogenic effect of physiologic high insulin in the portal vein. The upward arrow ↑ indicates an increase, and the downward arrow ↓ indicates a decrease. CEACAM1: Carcinoembryonic antigen-related cell adhesion molecule 1; IR: insulin receptor; FASN: fatty acid synthase.