Species-specific differences in agonistic activity of ago-allosteric modulators toward glucagon-like peptide 2 receptor

Yamazaki, Kazuto; Takase, Kazuma; Watanabe, Misako; Kagaya, Toshitaka; Terauchi, Hiroki; Iida, Daisuke; Fukumoto, Hironori; Suzuki, Shinichi; Arai, Tohru; Aoki, Mika; Seiki, Takashi; Tsukahara, Kappei; Nagakawa, Junichi

doi:10.2220/biomedres.33.337

Cited by 2 publications

(1 citation statement)

References 24 publications

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“…Because of the many effects of GLP-2 on the gut, therapies including long-acting GLP-2 derivatives or activators of GLP-2 secretion or the GLP-2R have been proposed for the treatment of intestinal disorders or conditions of humans to improve nutrient absorption and intestinal healing (reviewed by Wallis et al, 2007;Tee et al, 2011;Yamazaki et al, 2012;Drucker and Yusta, 2014). These conditions include short bowel syndrome (nutrient malabsorption generally due to intestinal resection); inflammatory bowel disease; colitis or colonic injury; enteritis caused by chemotherapies, prolonged nonsteroidal anti-inflammatory drug use, infectious agents, and radiation treatment; gut ischemia; necrotizing enterocolitis, particularly in premature infants; total parenteral nutrition-induced gut atrophy; and impaired gut barrier function (e.g., from acute necrotizing pancreatitis, diet-induced allergy, or stress).…”

Section: Applications In Nonruminantsmentioning

confidence: 99%

COMPARATIVE GUT PHYSIOLOGY SYMPOSIUM: Comparative physiology of glucagon-like peptide-2: Implications and applications for production and health of ruminants12

Connor

Evock‐Clover

Walker

et al. 2015

Journal of Animal Science

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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, in 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 and obesity-related disorders and to reduce cellular damage associated with inflammation of the gut and lungs. Recent studies demonstrate that many biological actions and properties of GLP-2 in ruminants are similar to those in nonruminants, including the potential to reduce intestinal nitro-oxidative stress in calves caused by parasitic diseases such as coccidiosis. Because of 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 because of 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.

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Section: Applications In Nonruminantsmentioning

confidence: 99%

COMPARATIVE GUT PHYSIOLOGY SYMPOSIUM: Comparative physiology of glucagon-like peptide-2: Implications and applications for production and health of ruminants12

Connor

Evock‐Clover

Walker

et al. 2015

Journal of Animal Science

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Modulating vertebrate physiology by genomic fine-tuning of GPCR functions

Schöneberg

2025

Physiological Reviews

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G protein-coupled receptors (GPCRs) play a crucial role as membrane receptors, facilitating the communication of eukaryotic species with their environment and regulating cellular and organ interactions. Consequently, GPCRs hold immense potential in contributing to adaptation to ecological niches and responding to environmental shifts. Comparative analyses of vertebrate genomes reveal patterns of GPCR gene loss, expansion, and signatures of selection. Integrating this genomic data with insights from functional analyses of gene variants enables the interpretation of genotype-phenotype correlations. This review underscores the involvement of GPCRs in adaptive processes, presenting numerous examples of how alterations in GPCR functionality influence vertebrate physiology, or conversely, how environmental changes impact GPCR functions. The findings demonstrate that modifications in GPCR function contribute to adapting to aquatic, arid, and nocturnal habitats, influencing camouflage strategies, and specializing in particular dietary preferences. Furthermore, the adaptability of GPCR functions provides an effective mechanism in facilitating past, recent, or ongoing adaptations in animal domestication and human evolution and should be considered in therapeutic strategies and drug development.

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Species-specific differences in agonistic activity of ago-allosteric modulators toward glucagon-like peptide 2 receptor

Abstract: Glucagon-like peptide 2 (GLP-2) is an intestinotropic peptide that binds to GLP-2 receptor (GLP-

Cited by 2 publications

References 24 publications

COMPARATIVE GUT PHYSIOLOGY SYMPOSIUM: Comparative physiology of glucagon-like peptide-2: Implications and applications for production and health of ruminants12

COMPARATIVE GUT PHYSIOLOGY SYMPOSIUM: Comparative physiology of glucagon-like peptide-2: Implications and applications for production and health of ruminants12

Modulating vertebrate physiology by genomic fine-tuning of GPCR functions

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