Leptin-induced Trafficking of K Channels: A Mechanism to Regulate Pancreatic β-cell Excitability and Insulin Secretion

The adipocyte hormone leptin was first recognized for its actions in the central nervous system to regulate energy homeostasis but has since been shown to have direct actions on peripheral tissues. In pancreatic β-cells leptin suppresses insulin secretion by increasing K channel conductance, which causes membrane hyperpolarization and renders β-cells electrically silent. However, the mechanism by which leptin increases K channel conductance had remained unresolved for many years following the initial observation. Recent studies have revealed that leptin increases surface abundance of K channels by promoting channel trafficking to the β-cell membrane. Thus, K channel trafficking regulation has emerged as a mechanism by which leptin increases K channel conductance to regulate β-cell electrical activity and insulin secretion. This review will discuss the leptin signaling pathway that underlies K channel trafficking regulation in β-cells.