Studies in vitro of equine intestinal glucagon-like peptide-2 secretion.
Abstract: Equine insulin dysregulation (ID) is a significant metabolic problem because the hyperinsulinaemia that develops increases the animal's risk of developing laminitis, a debilitating foot condition. The role of gastrointestinal factors, such as incretin hormones, in the pathogenesis of ID and hyperinsulinaemia in horses is poorly understood, particularly in comparison to other species. Glucagon-like peptide-2 (GLP-2) is an intestinotrophic peptide released from L cells in the gastrointestinal tract and is implicated in metabolic dysfunction in other species. The aim of this study in vitro was to establish basic physiological understanding about intestinal secretion of GLP-2 in horses. Basal and glucose-stimulated GLP-2 secretion was measured in post-mortem tissue samples from the duodenum, jejunum, and ileum. We observed that GLP-2 secretion was minimal in samples from the duodenum compared to the jejunum and ileum (5-9-fold higher; P < 0.05). Furthermore, GLP-2 secretion was not responsive to glucose stimulation in the ileum or duodenum but was responsive to glucose in the jejunum. This effect in the jejunum was inhibited by 30 % (P = 0.02) using phlorizin, a selective sodium-glucose cotransporter-1 (SGLT-1) inhibitor, and by 38 % (P = 0.04) using phloretin, a non-selective SGLT-1/GLUT-2 inhibitor. The localisation of glucose-responsive GLP-2 secretion in the jejunum might be relevant to the development of post-prandial hyperinsulinaemia. This study has provided data on GLP-2 secretion from the equine small intestine that will enable more complex and dynamic studies on the pathogenesis of ID.
Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.
Publication Date: 2024-08-26 PubMed ID: 39197558DOI: 10.1016/j.jevs.2024.105179Google Scholar: Lookup
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- Journal Article
Summary
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The research investigates how glucagon-like peptide-2 (GLP-2), an intestinotrophic hormone, behaves in the horse’s digestive system. The focus is on basal and glucose-stimulated GLP-2 secretion, its response to glucose in different areas of the intestine, and how it might be linked to insulin dysregulation (ID) in horses.
Objective of the Research
- The study aims to explore the role of glucagon-like peptide-2 (GLP-2) in the horse’s intestinal tract in relation to horse metabolic issues such as insulin dysregulation (ID) and hyperinsulinaemia, conditions known to increase the risk of laminitis, a painful and often devastating foot disease in horses.
Research Methodology
- The research was conducted in vitro with post-mortem tissue samples from the duodenum, jejunum, and ileum areas of the horse’s small intestine.
- The researchers measured both naturally occurring (basal) and glucose-stimulated secretion of GLP-2.
- They used inhibitors such as phlorizin, a selective sodium-glucose cotransporter-1 (SGLT-1) inhibitor, and phloretin, a non-selective SGLT-1/GLUT-2 inhibitor, to analyze the GLP-2’s response.
Key Findings
- GLP-2 secretion was found to be minimal in the duodenum and significantly higher (by 5-9 times) in the jejunum and ileum.
- The GLP-2 hormone’s secretion did not respond to glucose stimulation in the ileum or duodenum, but showed a significant response in the jejunum.
- The response in the jejunum was reduced by approximately 30% with the use of phlorizin, and by 38% with phloretin.
Conclusion and Further Implication
- The study concluded that the location of glucose-responsive GLP-2 secretion in the jejunum could be potentially significant to the development of post-prandial hyperinsulinaemia, suggesting a specific role of this part of the intestine in ID.
- This discovery opens avenues for more complex and dynamic studies in understanding not only GLP-2 secretion but also the pathogenesis of insulin dysregulation in horses.
Cite This Article
APA
Sibthorpe PEM, Fitzgerald DM, Sillence MN, de Laat MA.
(2024).
Studies in vitro of equine intestinal glucagon-like peptide-2 secretion.
J Equine Vet Sci, 142, 105179.
https://doi.org/10.1016/j.jevs.2024.105179 Publication
Researcher Affiliations
- School of Biology and Environmental Science, Queensland University of Technology, Brisbane, Queensland, Australia.
- School of Biology and Environmental Science, Queensland University of Technology, Brisbane, Queensland, Australia.
- School of Biology and Environmental Science, Queensland University of Technology, Brisbane, Queensland, Australia.
- School of Biology and Environmental Science, Queensland University of Technology, Brisbane, Queensland, Australia. Electronic address: melody.delaat@qut.edu.au.
MeSH Terms
- Animals
- Horses
- Glucagon-Like Peptide 2 / metabolism
- Glucose / metabolism
- Gene Expression Regulation / drug effects
- Jejunum / metabolism
- Jejunum / pathology
Conflict of Interest Statement
Declaration of competing interest None of the authors has any financial or personal relationships that could inappropriately influence or bias the content of the paper.
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