Comparative Physiology of Glucagon-like Peptide 2 - Implications and Applications for Production and Health of Ruminants

Abstract Text: Glucagon-like peptide 2 (GLP-2) is a 33-amino acid peptide derived from proteolytic cleavage of proglucagon by prohormone convertase 1/3 in enteroendocrine L-cells. Studies conducted in humans, rodent models, and in vitro indicate that GLP-2 is secreted in response to the presence of molecules in the intestinal lumen including fatty acids, carbohydrates, amino acids, and bile acids, which are detected by luminal chemosensors. The physiological actions of GLP-2 are mediated by its G-protein coupled receptor expressed primarily in the intestinal tract on enteric neurons, enteroendocrine cells, and myofibroblasts. The biological activity of GLP-2 is further regulated by dipeptidyl peptidase IV, which rapidly cleaves the N-terminus of GLP-2 that is responsible for GLP-2 receptor activation. Within the gut, GLP-2 increases nutrient absorption, crypt cell proliferation, and mesenteric blood flow, and decreases gut permeability and motility, epithelial cell apoptosis, and inflammation. Outside the gut, GLP-2 reduces bone resorption, can suppress appetite, and is cytoprotective in the lung. Thus, GLP-2 has been studied intensively as a therapeutic to improve intestinal function of humans during parenteral nutrition and following small bowel resection, and more recently, as a treatment for osteoporosis, obesity-related disorders, and to reduce cellular damage associated with inflammation of the gut and lungs. Recent studies demonstrate that GLP-2 has many similar biological actions and properties in ruminants as in monogastrics, including the potential to reduce intestinal nitro-oxidative stress in calves caused by parasitic diseases like coccidiosis. Due to its beneficial impacts on nutrient absorption, gut healing, and normal gut development, GLP-2 therapy offers significant opportunities to improve calf health and production efficiency. However, GLP-2 therapies require an extended time course to achieve desired physiological responses, as well as daily administration due to the hormone’s short half life. Thus practical means of administration and alternative strategies to enhance basal GLP-2 secretion (e.g., through specific feed additives), which are more likely to achieve consumer acceptance, are needed. Opportunities to address these challenges are discussed.

Keywords: Cattle, Glucagon-like peptide-2, Gut health