Proglucagon (GCG)

Proglucagon is a 160-amino acid precursor protein encoded by the GCG gene, primarily synthesized in the pancreatic alpha cells, intestinal L-cells, and specific neurons in the brainstem [1][2]. It undergoes tissue-specific proteolytic processing by prohormone convertases (PC1/3 and PC2) to generate several biologically active peptides, including glucagon, glucagon-like peptide-1 (GLP-1), glucagon-like peptide-2 (GLP-2), oxyntomodulin, and glicentin [1][3]. Glucagon is essential for elevating blood glucose during fasting by stimulating hepatic glycogenolysis and gluconeogenesis, while GLP-1 acts as an incretin hormone to enhance glucose-dependent insulin secretion and promote satiety [3][4]. GLP-2 is critical for maintaining intestinal mucosal integrity and nutrient absorption [4]. Consequently, the proglucagon system is a major therapeutic focus; GLP-1 receptor agonists are widely used for the treatment of type 2 diabetes and obesity, while GLP-2 analogs are utilized for short bowel syndrome [5]. Drugs targeting this pathway typically function as stable mimics of these endogenous peptides to modulate metabolic and physiological processes [5].

Other names

Glucagon-precursorGCGGlicentinOxyntomodulinGlucagon-like peptide 1Glucagon-like peptide 2Glicentin-related pancreatic polypeptide

Agonism of the Glucagon-like peptide 1 receptor (GLP-1R), Glucagon receptor (GCGR), or Glucagon-like peptide 2 receptor (GLP-2R) by synthetic analogs of proglucagon-derived peptides.