Enteroglucagon

Abstract

The gene encoding proglucagon, the biosynthetic precursor of glucagon, is expressed not only in the pancreatic islets but also in endocrine cells of the gastrointestinal mucosa. The proglucagon (PG)-derived peptides from the gut include glicentin (corresponding to PG 1-69); smaller amounts of oxyntomodulin (PG 33-69) and glicentin-related pancreatic polypeptide (GRPP, PG 1-30); glucagon-like peptide-1 (GLP-1, PG 78-107 amide); intervening peptide-2 (IP-2, PG 111-122 amide); and glucagon-like peptide-2 (GLP-2, PG 126-158). All are secreted into the blood in response to ingestion of carbohydrates and lipids. Only oxyntomodulin and GLP-1 have proven biological activity; oxyntomodulin possibly because it interacts (but with lower potency) with GLP-1 and glucagon receptors. GLP-1 is the most potent insulinotropic hormone known and functions as an incretin hormone. It also inhibits glucagon secretion and, therefore, lowers blood glucose. This effect is preserved in patients with non-insulin-dependent diabetes mellitus, in whom infusions of GLP-1 may completely normalize blood glucose. However, GLP-1 also potently inhibits gastrointestinal secretion and motility, and its physiological functions include mediation of the "ileal-brake" effect, i.e. the inhibition of upper gastrointestinal functions elicited by the presence of unabsorbed nutrients in the ileum. As such it may serve to regulate food intake.