Teduglutide, a glucagon-like peptide 2 analogue: A novel protective agent with anti-apoptotic and anti-oxidant properties in mice with lung injury

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

“…Although GLP-2 is primarily known for its effects on the gastrointestinal tract, expression of GLP-2R and physiological effects of GLP-2 beyond the gut have been reported, including on pancreas, brain, bone [28], lung [11], and liver [10]. These effects of GLP-2 influence glucose metabolism, feed intake, bone resorption, and lung and liver healing postinjury, all which could have implications for the therapeutic use of GLP-2 in livestock animal production, and will be discussed briefly.…”

“…Although these effects were based on central administration of GLP-2, it is believed that peripheral GLP-2 (both physiological and pharmacologic doses) may be able to cross the blood-brain barrier and have central effects [12]. Finally, GLP-2 has been shown to improve liver regeneration after injury in a mouse model using partial hepatectomy [10], to reduce bone resorption and improve bone mineral density in humans, particularly postmenopausal women [86], and to enhance lung recovery in mice after inflammation-related oxidative damage [11]. Thus, in the development of any GLP-2 treatment regimen, the potential effects on GLP-2R-mediated activities within the central nervous system and other tissues outside the gastrointestinal tract should be considered.…”

“…Furthermore, GLP-2 may be useful for ameliorating damage to the liver and lungs, particularly resulting from inflammation and overproduction of proinflammatory mediators during an immune challenge, based on its effects on these tissues described previously in mice [10,11]. Although the direct effects of GLP-2 on liver and lung health of livestock have not been evaluated, feeding of aspartate for 20 d to weanling pigs was shown to affect mRNA expression of proinflammatory signaling molecules in the toll-like receptor 4 and nuclear-binding and oligomerization domain pathways that modulate innate and adaptive immune function, and to improve serum indicators of liver damage after an intraperitoneal LPS challenge [109].…”

“…In the lungs, treatment with a long-acting form of GLP-2 reduced apoptosis and oxidative stress-induced injury in mice in response to an intraperitoneal challenge with proinflammatory tumor necrosis factor-a and actinomycin D [11]. These benefits have particular relevance to common respiratory diseases of livestock, such as shipping fever in cattle caused by Pasteruella (Mannheimia) haemolytica.…”

“…Since that time, numerous subtypes of endocrine cells within the intestinal mucosa and their peptide products have been characterized [2]. These enteric peptides have become the subject of intensive scientific investigation regarding regulation of their release [3][4][5], mechanisms of action [6][7][8], and diverse physiological effects, including those outside the digestive system such as bone [9], liver [10], lung [11], and the central nervous system [12][13][14]. This primarily was due to the discovery that enteric peptides, such as glucagon-like peptide 1 (GLP-1), gastric inhibitory peptide, and peptide YY, play key roles in the regulation of appetite, energy metabolism [15][16][17], and gut function [18][19][20], making them targets for managing prevalent human diseases of obesity and diabetes.…”