Monitoring Glucagon and Glucagon Antagonist-Mediated Internalization: A Useful Approach to Study Glucagon Receptor Pharmacology

摘要

The impetus for studying how glucagon interacts with its receptor is to gain insight into the mechanism of glucagon action in normal physiology as well as in diabetes mellitus [1]. Continued interest in the glucagon receptor as a drug target for diabetes management is sustained by studies that show that treatment with glucagon antagonists has restored glucose homeostasis. Glucagon binding leads to internalization of glucagon receptors, a well-characterized phenomenon for GPCRs [2]. Upon activation, receptors are sequestered from the cell surface into cellular compartments where they are either recycled or targeted for degradation. Recently, studies have linked ligand-induced receptor internalization to pharmacological properties measured by conventional cell-based assays. Moreover, GPCR trafficking assays in live cells can be monitored by the use of fluorescent reagents and used to evaluate differences between agonist and antagonist effects on internalization [3,4].