Figure 3.

Insulin clearance in the liver. (A) Insulin is delivered to the hepatic sinusoid, where it freely accesses the liver hepatocytes through the fenestrated sinusoidal endothelium. (B) Proposed mechanism for insulin degradation in hepatocytes. Insulin binds to the IR and forms a complex with CEACAM1. Prior to internalization, extracellular IDE begins to degrade receptor-bound insulin. After internalization, endosomal IDE degrades receptor-bound insulin and, once the endosome acidifies and the complex dissociates, also frees insulin. Any remaining insulin or insulin fragments progress toward lysosomes for their complete proteolytic degradation.