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Equine veterinary journal2023; doi: 10.1111/evj.14020

Expression of the GCG gene and secretion of active glucagon-like peptide-1 varies along the length of intestinal tract in horses.

Abstract: Active glucagon-like peptide-1 (aGLP-1) has been implicated in the pathogenesis of equine insulin dysregulation (ID), but its role is unclear. Cleavage of proglucagon (coded by the GCG gene) produces aGLP-1 in enteral L cells. Objective: The aim in vivo was to examine the sequence of the exons of GCG in horses with and without ID, where aGLP-1 was higher in the group with ID. The aims in vitro were to identify and quantify the expression of GCG in the equine intestine (as a marker of L cells) and determine intestinal secretion of aGLP-1. Methods: Genomic studies were case-control studies. Expression and secretion studies in vitro were cross-sectional. Methods: The GCG gene sequence of the exons was determined using a hybridisation capture protocol. Expression and quantification of GCG in samples of stomach duodenum, jejunum, ileum, caecum and ascending and descending colon was achieved with droplet digital PCR. For secretory studies tissue explants were incubated with 12 mM glucose and aGLP-1 secretion was measured with an ELISA. Results: Although the median [IQR] post-prandial aGLP-1 concentrations were higher (p = 0.03) in animals with ID (10.2 [8.79-15.5]), compared with healthy animals (8.47 [6.12-11.7]), there was 100% pairwise identity of the exons of the GCG sequence for the cohort. The mRNA concentrations of GCG and secretion of aGLP-1 differed (p < 0.001) throughout the intestine. Conclusions: Only the exons of the GCG gene were sequenced and breeds were not compared. The horses used for the study in vitro were not assessed for ID and different horses were used for the small, and large, intestinal studies. Conclusions: Differences in post-prandial aGLP-1 concentration were not due to a variant in the exons of the GCG gene sequence in this cohort. Both the large and small intestine are sites of GLP-1 secretion.
© 2023 The Authors. Equine Veterinary Journal published by John Wiley & Sons Ltd on behalf of EVJ Ltd.
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Publication Date: 2023-10-18 PubMed ID: 37853957DOI: 10.1111/evj.14020Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The study investigates the expression and secretion of active glucagon-like peptide-1 (aGLP-1), a diabetes-related hormone, across various sections of the horse intestine. This helps understand the role of aGLP-1 in equine insulin dysregulation. The researchers found no variations in the gene that codes for aGLP-1 between horses with and without insulin dysregulation.

Objective and Methods

  • The research aimed to explore potential variants in the GCG gene, which codes for the hormone aGLP-1 involved in insulin regulation, in horses with and without insulin dysregulation.
  • The researchers also aimed to establish the distribution and quantity of GCG expression, as well as aGLP-1 secretion across various sections of the horse intestine in vitro.
  • The sequence of the exons of GCG gene in horses was determined using a hybridisation capture protocol. This is a molecular technique that helps determine the sequence of specific parts of the genome.
  • Quantification of GCG in samples of stomach duodenum, jejunum, ileum, caecum and colon was achieved using droplet digital PCR, a highly precise method for counting DNA molecules.
  • The researchers also conducted secretory studies, where tissue samples were exposed to glucose to stimulate aGLP-1 secretion, which was then measured using an ELISA.

Results

  • Post-prandial (after mealtime) aGLP-1 concentrations were higher in horses with insulin dysregulation. However, there were no differences found in the exons of the GCG gene sequence between the healthy and insulin dysregulated horses.
  • GCG gene expression and aGLP-1 secretion varied significantly throughout the horse intestine.

Conclusion

  • The researchers concluded that the differences in aGLP-1 concentrations post meals were not due a variant in the exons of the GCG gene sequence.
  • aGLP-1 secretion was observed in both the small and large intestines.
  • The conclusions are limited as only the exons of the GCG gene were sequenced and the breeds of horses were not compared.
  • The same set of horses were not used to study both small and large intestines, and they were not assessed for insulin dysregulation before carrying out the study.

Cite This Article

APA
Fitzgerald DM, Cash CM, Dudley KJ, Sibthorpe PEM, Sillence MN, de Laat MA. (2023). Expression of the GCG gene and secretion of active glucagon-like peptide-1 varies along the length of intestinal tract in horses. Equine Vet J. https://doi.org/10.1111/evj.14020

Publication

Equine veterinary journal
ISSN: 2042-3306
NlmUniqueID: 0173320
Country: United States
Language: English

Researcher Affiliations

Fitzgerald, Danielle M
  • Faculty of Science, Queensland University of Technology, Brisbane, Queensland, Australia.
Cash, Christina M
  • Faculty of Science, Queensland University of Technology, Brisbane, Queensland, Australia.
Dudley, Kevin J
  • Faculty of Science, Queensland University of Technology, Brisbane, Queensland, Australia.
Sibthorpe, Poppy E M
  • Faculty of Science, Queensland University of Technology, Brisbane, Queensland, Australia.
Sillence, Martin N
  • Faculty of Science, Queensland University of Technology, Brisbane, Queensland, Australia.
de Laat, Melody A
  • Faculty of Science, Queensland University of Technology, Brisbane, Queensland, Australia.

Grant Funding

  • DP180102418 / Australian Research Council

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Citations

This article has been cited 1 times.
  1. de Laat MA, Fitzgerald DM, Harris PA, Bailey SR. A glucagon-like peptide-1 receptor antagonist reduces the insulin response to a glycemic meal in ponies. J Anim Sci 2023 Jan 3;101.
    doi: 10.1093/jas/skad389pubmed: 38066683google scholar: lookup
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