Affiliation:
1. Department of Medical Physiology, the Panum Institute, University of Copenhagen, DK 2200 Copenhagen N, Denmark
Abstract
▪ 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.
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290 articles.
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