Insulin Clearance in Health and Disease

Insulin action is impaired in type 2 diabetes. The functions of the hormone are an integrated product of insulin secretion from pancreatic β-cells and insulin clearance by receptor-mediated endocytosis and degradation, mostly in liver (hepatocytes) and, to a lower extent, in extrahepatic peripheral tissues. Substantial evidence indicates that genetic or acquired abnormalities of insulin secretion or action predispose to type 2 diabetes. In recent years, along with the discovery of the molecular foundation of receptor-mediated insulin clearance, such as through the membrane glycoprotein CEACAM1, a consensus has begun to emerge that reduction of insulin clearance contributes to the disease process. In this review, we consider the evidence suggesting a pathogenic role for reduced insulin clearance in insulin resistance, obesity, hepatic steatosis, and type 2 diabetes.