Insulin Clearance Along the Liver–Kidney Axis: Implications for Insulin Action

The pleiotropic actions of insulin are mediated by cascades of signaling pathways and are regulated by circulating insulin levels. Under physiologic conditions, insulin levels reflect the balance between pancreatic beta-cell secretion and insulin clearance, which occurs primarily in liver hepatocytes and, to a lesser extent, in kidney proximal tubule cells. Therefore, coordination between insulin secretion and clearance is essential for systemic insulin sensitivity. Whereas insulin secretion is widely investigated, exploring the role of insulin clearance in regulating insulin sensitivity remains limited. This review summarizes the main mechanisms underlying insulin clearance along the liver–kidney axis and discusses how they contribute to metabolic regulation in health and disease.