Glucagon-like peptide 2 and its beneficial effects on gut function and health in production animals

Abstract

Numerous endocrine cell subtypes exist within the intestinal mucosa and produce peptides contributing to the regulation of critical physiological processes including appetite, energy metabolism, gut function, and gut health. The mechanisms of action and the extent of the physiological effects of these enteric peptides are only beginning to be uncovered. One peptide in particular, glucagon-like peptide 2 (GLP-2) produced by enteroendocrine L cells, has been fairly well characterized in rodent and swine models in terms of its ability to improve nutrient absorption and healing of the gut after injury. In fact, a long-acting form of GLP-2 recently has been approved for the management and treatment of human conditions like inflammatory bowel disease and short bowel syndrome. However, novel functions of GLP-2 within the gut continue to be demonstrated, including its beneficial effects on intestinal barrier function and reducing intestinal inflammation. As knowledge continues to grow about GLP-2's effects on the gut and its mechanisms of release, the potential to use GLP-2 to improve gut function and health of food animals becomes increasingly more apparent. Thus, the purpose of this review is to summarize: (1) the current understanding of GLP-2's functions and mechanisms of action within the gut; (2) novel applications of GLP-2 (or stimulators of its release) to improve general health and production performance of food animals; and (3) recent findings, using dairy calves as a model, that suggest the therapeutic potential of GLP-2 to reduce the pathogenesis of intestinal protozoan infections.

Characterizing effects of feed restriction and glucagon-like peptide 2 administration on biomarkers of inflammation and intestinal morphology

“…This can undoubtedly compromise production as immunoactivation is an energetically expensive process that redirects energy away from agriculturally productive purposes and compromises animal welfare (Johnson, 2012;Kvidera et al, 2017b). Therefore, assessing molecules or nutritional strategies to ameliorate gut barrier dysfunction, including exogenous GLP2, has gained recent attention in production agriculture (Thymann et al, 2014;Connor et al, 2016). Endog-enous GLP2 is a proglucagon-derived peptide secreted by enteroendocrine L cells in response to luminal nutrients (Drucker and Yusta, 2014).…”

“…Endog-enous GLP2 is a proglucagon-derived peptide secreted by enteroendocrine L cells in response to luminal nutrients (Drucker and Yusta, 2014). The intestinal trophic effects of GLP2 are mediated through increased mesenteric blood flow, greater nutrient uptake, and release of growth factors such as IGF-1, IGF-2, keratinocyte growth factor, and epidermal growth factor-ErbB family members (Connor et al, 2016). Exogenous GLP2 administration reduced intestinal permeability, hepatic bacterial cultures, and intestinal crypt apoptosis in stressed mouse models (Boushey et al, 1999;Cameron and Perdue, 2005).…”

“…Decreased intestinal barrier integrity has several negative consequences and thus research into ruminant intestinal health has gained recent attention (Connor et al, 2016;Steele et al, 2016). However, it is difficult to model leaky gut to test potential mitigation strategies.…”

Current Knowledge of Necrotizing Enterocolitis in Preterm Infants and the Impact of Different Types of Enteral Nutrition Products

“…The authors did not specify whether the polymeric formula was bovine milk-based, but this was likely the case. The outcomes of interest were functional and structural adaptations of the intestine, as well as glucagon-like peptide 2 (GLP-2), a gut-specific hormone that improves nutritional absorption and intestinal barrier function (87). No difference was found in structural measures such as intestinal lengthening, villus height, crypt depth, and colon weight between the diet groups.…”

Gastrointestinal defense mechanisms

“…GLP-1 is highly expressed in enteroendocrine L-cells throughout the gastrointestinal tract, where it serves as an incretin that helps maintain glycemic control. Like GLP-1, GLP-2, also expressed in L-cells, has many intestinotrophic properties, such as increasing the rate of crypt enterocyte proliferation, increasing the rate of mesenteric artery blood flow, and increasing crypt-villus depth [9]. The GLP-2 receptor (GLP-2R) is expressed in subepthelial pericryptal myofibroblasts and enteric neurons, which further support its proposed function as major intermediate in many cell-signaling pathways [10, 11].…”