Role of Insulin Clearance in Insulin Action and Metabolic Diseases

Abstract

The year 2021 marked the centenary of the discovery of insulin. Since its discovery, investigations have focused on how insulin secretion from pancreatic beta cells triggers branching signaling pathways to mediate its physiological actions. Secreted in pulses into the portal circulation, insulin binds to cell surface receptors on hepatocytes through fenestrations of endothelial cells lining the hepatic sinusoid. This triggers its rapid receptormediated internalization and targeting for degradation to be cleared from circulation. Insulin degradation constitutes the basic mechanism of hepatic insulin clearance. In recent years, this process has gained traction since it has been found to contribute to determining the physiologic levels of insulin reaching post-hepatic tissues and, subsequently, regulate systemic insulin action. This Special Issue, entitled “Role of Insulin Clearance in Insulin Action and Metabolic Diseases”, focuses on the body of work delineating the molecular mechanisms of altered insulin clearance and its role in the pathogenesis of dysregulated metabolism.