Proglucagonderived

Proglucagon-derived peptides are a family of peptide hormones and related fragments produced from the proglucagon precursor, encoded by the GCG gene. The proglucagon precursor is differentially processed in distinct tissues by prohormone convertases, yielding tissue-specific sets of peptides that regulate metabolism, gut function, and energy balance.

In pancreatic alpha cells, proglucagon is cleaved primarily by prohormone convertase 2 to produce glucagon, which acts to raise blood glucose by promoting hepatic glucose production. In intestinal L cells and certain neurons, proglucagon is cleaved mainly by prohormone convertase 1/3 to generate glucagon-like peptides, notably glucagon-like peptide-1 (GLP-1) and glucagon-like peptide-2 (GLP-2), as well as oxyntomodulin and glicentin. These derivatives can be further processed by enzymes such as dipeptidyl peptidase-4 (DPP-4), generating active metabolites with distinct half-lives and activities.

GLP-1 is a key incretin that enhances glucose-stimulated insulin secretion and suppresses glucagon release, contributing to postprandial glucose regulation. GLP-2 has trophic effects on the intestinal mucosa, supporting nutrient absorption and gut health. Oxyntomodulin is associated with appetite suppression and energy balance, while glicentin and other products have roles that are still being clarified, particularly in gut motility and metabolism.

Clinical relevance includes the use of GLP-1 receptor agonists and DPP-4 inhibitors in the treatment of type 2 diabetes and obesity, reflecting the central role of proglucagon-derived peptides in metabolic regulation. Dysregulation of this system is linked to metabolic disorders and gastrointestinal diseases.