New frontiers in the biology of GLP-2.
Glucagon-like peptide-2 (GLP-2) is a 33 amino acid peptide hormone released from the intestinal endocrine cells following nutrient ingestion. GLP-2 exerts trophic effects on the small and large bowel epithelium via stimulation of cell proliferation and inhibition of apoptosis. GLP-2 also upregulates intestinal glucose transporter activity, and reduces gastric emptying and gastric acid secretion. The activity of GLP-2 is regulated in part via renal clearance and cleavage by the aminopeptidase dipeptidyl peptidase IV. In experimental models of intestinal disease, GLP-2 reversed parenteral nutrition-induced mucosal atrophy and accelerated the process of endogenous intestinal adaptation in rats following major small bowel resection. GLP-2 also markedly attenuated intestinal injury and weight loss in mice with chemically-induced colitis, and significantly reduced mortality, bacterial infection and intestinal mucosal damage in mice with indomethacin-induced enteritis. The actions of GLP-2 are transduced by a recently cloned glucagon-like peptide-2 receptor (GLP-2R) that represents a new member of the G protein-coupled receptor superfamily. The GLP-2R is expressed in a highly tissue-specific manner predominantly in the gastrointestinal tract and GLP-2R activation is coupled to increased adenylate cyclase activity. The available evidence suggests that the biological properties of GLP-2 merit careful therapeutic assessment in selected human diseases characterized by injury and defective repair of the gastrointestinal epithelium.
Lovshin
J
J
Toronto General Hospital, Department of Medicine, Banting and Best Diabetes Centre, 101 College Street, M5G 1L5, Toronto, Canada.
Drucker
D J
DJ
D000818:Animals; D005544:Forecasting; D053767:Glucagon-Like Peptide 2; D000067757:Glucagon-Like Peptide-1 Receptor; D004763:Glucagon-Like Peptides; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy; D007422:Intestines / Q000293:injuries; D051379:Mice; D010455:Peptides / Q000378:metabolism / Q000502:physiology* / Q000627:therapeutic use; D051381:Rats; D018027:Receptors, Glucagon / Q000378:metabolism
C000593833:GLP1R protein, human; C000593834:Glp1r protein, mouse; C000593835:Glp1r protein, rat; D053767:Glucagon-Like Peptide 2; D000067757:Glucagon-Like Peptide-1 Receptor; D010455:Peptides; D018027:Receptors, Glucagon; D004763:Glucagon-Like Peptides