Definition
The receptor for glucagon, regulating hepatic glucose output and lipid metabolism; a target of triple agonists.
The glucagon receptor is a class B G protein-coupled receptor expressed mainly in the liver, with expression also in the kidney and adipose tissue. Glucagon, a 29-residue peptide from pancreatic alpha cells, acts on it to raise hepatic glucose output and influence lipid metabolism. In rodent models, glucagon receptor agonism increases energy expenditure, which is the rationale for combining it with incretin agonism. The design challenge is balance, because glucagon raises blood glucose while GLP-1 lowers it. Retatrutide combines glucagon, GIP and GLP-1 receptor activity, while survodutide and mazdutide combine glucagon and GLP-1 receptor activity.