preproglucagon

Preproglucagon is the precursor polypeptide encoded by the GCG gene. It is synthesized with an N-terminal signal peptide that directs the molecule into the secretory pathway; removal of the signal peptide produces proglucagon, a larger precursor that is differentially processed in different tissues.

In pancreatic alpha cells, proglucagon is cleaved primarily by prohormone convertase 2 (PC2) to yield glucagon and smaller peptides such as the intervening peptide and other byproducts. In intestinal L cells, proglucagon is cleaved mainly by prohormone convertase 1/3 (PC1/3) to produce glucagon-like peptides including GLP-1 and GLP-2, as well as related peptides such as oxyntomodulin and glicentin. The exact set of peptides produced depends on tissue-specific processing by these convertases and related proteases.

The peptides produced from preproglucagon have diverse roles. Glucagon acts on the liver to raise blood glucose levels by promoting glycogenolysis and gluconeogenesis. GLP-1 and other glucagon-derived peptides potentiate glucose-dependent insulin secretion and inhibit glucagon release, contributing to postprandial glucose control. GLP-2 promotes intestinal mucosal growth and function, while oxyntomodulin can influence appetite and energy balance. Glicentin and related fragments have regulatory roles in gut motility and nutrient absorption, though their precise functions are less well defined.

Clinically, dysregulation of glucagon and GLP-1 pathways is implicated in metabolic disorders such as type 2 diabetes. Therapeutic strategies increasingly target GLP-1 signaling, including GLP-1 receptor agonists and modifiers of glucagon action. Research on preproglucagon and its derived peptides informs understanding of glucose homeostasis, appetite regulation, and gastrointestinal physiology.