Glucagon-like Peptide 2 Function in Domestic Animals

Glucagon-like peptide 2 (GLP-2) is a member of family of peptides derived from the proglucagon gene expressed in the intestines, pancreas and brain. Tissue-specific posttranslational processing of proglucagon leads to GLP-2 and GLP-1 secretion from the intestine and glucagon secretion from the pancreas. GLP-2 and GLP-1 are co-secreted from the enteroendocrine L-cells located in distal intestine in response to enteral nutrient ingestion, especially carbohydrate and fat. GLP-2 secretion is mediated by direct nutrient stimulation of the L-cells and indirect action from enteroendocrine and neural inputs, including GIP, gastrin-releasing peptide (GRP) and the vagus nerve. GLP-2 is secreted as a 33-amino acid peptide and is rapidly cleaved by dipeptidylpeptidase IV (DPP-IV) to a truncated peptide which acts as a weak agonist with competitive antagonistic properties. GLP-2 acts to enhance nutrient absorption by inhibiting gastric motility and secretion and stimulating nutrient transport. GLP-2 also suppresses food intake when infused centrally. The trophic actions of GLP-2 are specific for the intestine and occur via stimulation of crypt cell proliferation and suppression of apoptosis in mucosal epithelial cells. GLP-2 reduces gut permeability, bacterial translocation and proinflammatory cytokine expression under conditions of intestinal inflammation and injury. The effects of GLP-2 are mediated by a G-protein-linked receptor that is localized to the intestinal mucosa and hypothalamus. The intestinal localization of the GLP-2R to neural and endocrine cells, but not enterocytes, suggests that its actions are mediated indirectly via a secondary signaling mechanism. The implications of GLP-2 in domestic animal production are largely unexplored. However, GLP-2 may have therapeutic application in treatment of gastrointestinal injury and diarrheal diseases that occur in developing neonatal and weanling animals.