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Home / Equine Research Bank / PeerJ / Equine glucagon-like peptide-1 receptor physiology.
PeerJ2018; 6; e4316; doi: 10.7717/peerj.4316

Equine glucagon-like peptide-1 receptor physiology.

Abstract: Equine metabolic syndrome (EMS) is associated with insulin dysregulation, which often manifests as post-prandial hyperinsulinemia. Circulating concentrations of the incretin hormone, glucagon-like peptide-1 (GLP-1) correlate with an increased insulin response to carbohydrate intake in animals with EMS. However, little is known about the equine GLP-1 receptor (eGLP-1R), or whether GLP-1 concentrations can be manipulated. The objectives were to determine (1) the tissue localisation of the eGLP-1R, (2) the GLP-1 secretory capacity of equine intestine in response to glucose and (3) whether GLP-1 stimulated insulin secretion from isolated pancreatic islets can be attenuated. Methods: Archived and abattoir-sourced tissues from healthy horses were used. Reverse transcriptase PCR was used to determine the tissue distribution of the eGLP-1R gene, with immunohistochemical confirmation of its pancreatic location. The GLP-1 secretion from intestinal explants in response to 4 and 12 mM glucose was quantified . Pancreatic islets were freshly isolated to assess the insulin secretory response to GLP-1 agonism and antagonism , using concentration-response experiments. Results: The eGLP-1R gene is widely distributed in horses (pancreas, heart, liver, kidney, duodenum, digital lamellae, tongue and gluteal skeletal muscle). Within the pancreas the eGLP-1R was immunolocalised to the pancreatic islets. Insulin secretion from pancreatic islets was concentration-dependent with human GLP-1, but not the synthetic analogue exendin-4. The GLP-1R antagonist exendin 9-39 (1 nM) reduced ( = 0.08) insulin secretion by 27%. Conclusions: The distribution of the eGLP-1R across a range of tissues indicates that it may have functions beyond insulin release. The ability to reduce insulin secretion, and therefore hyperinsulinemia, through eGLP-1R antagonism is a promising and novel approach to managing equine insulin dysregulation.
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Publication Date: 2018-01-29 PubMed ID: 29404215PubMed Central: PMC5793710DOI: 10.7717/peerj.4316Google 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 research article studies the function and location of the glucagon-like peptide-1 (GLP-1) receptor in horses, its role in equine metabolic syndrome (EMS), and how it might be manipulated to handle insulin regulation issues within equine physiology.

Objectives and Methods

  • This study has three main objectives. Firstly, the researchers wanted to determine the tissue location of the GLP-1 receptor in horses. Secondly, they aimed to explore how the equine intestine releases GLP-1 upon glucose stimulation. Lastly, the study sought to investigate if insulin secretion, stimulated by GLP-1 from isolated pancreatic islets, could be reduced.
  • The scientists used a technique called reverse transcriptase PCR to determine where the eGLP-1R gene is distributed in the horse tissues. They confirmed its location in the pancreas through immunohistochemical methods.
  • The release of GLP-1 from intestinal tissues in response to varying glucose concentrations (4 and 12 mM) was measured.
  • Researchers freshly isolated pancreatic islets to assess the response of insulin secretion to GLP-1 manipulation, using concentration-response experiments.

Results

  • The eGLP-1R gene was identified in a range of tissues in horses, including the pancreas, heart, liver, kidney, tongue, duodenum, digital lamellae, and gluteal skeletal muscle. It was specifically located within the pancreatic islets.
  • There was a concentration-dependent insulin secretion from pancreatic islets with human GLP-1, but not with the synthetic analogue exendin-4.
  • The use of the GLP-1R antagonist exendin 9-39 managed to reduce insulin secretion by 27%, although the results weren’t particularly strong (P = 0.08).

Conclusions

  • The wide distribution of the eGLP-1R in various tissues indicates that it might have roles beyond influencing insulin release.
  • The study suggests that the ability to control insulin secretion, and thus hyperinsulinemia, through antagonizing the eGLP-1R could be a promising and innovative approach to managing insulin dysregulation in horses.

Cite This Article

APA
Kheder MH, Bailey SR, Dudley KJ, Sillence MN, de Laat MA. (2018). Equine glucagon-like peptide-1 receptor physiology. PeerJ, 6, e4316. https://doi.org/10.7717/peerj.4316

Publication

PeerJ
ISSN: 2167-8359
NlmUniqueID: 101603425
Country: United States
Language: English
Volume: 6
Pages: e4316
PII: e4316

Researcher Affiliations

Kheder, Murad H
  • Science and Engineering Faculty, Queensland University of Technology, Brisbane, Queensland, Australia.
Bailey, Simon R
  • Faculty of Veterinary and Agricultural Sciences, University of Melbourne, Melbourne, Victoria, Australia.
Dudley, Kevin J
  • Institute for Future Environments, Queensland University of Technology, Brisbane, Queensland, Australia.
Sillence, Martin N
  • Science and Engineering Faculty, Queensland University of Technology, Brisbane, Queensland, Australia.
de Laat, Melody A
  • Science and Engineering Faculty, Queensland University of Technology, Brisbane, Queensland, Australia.

Conflict of Interest Statement

The authors declare there are no competing interests.

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Citations

This article has been cited 5 times.
  1. Stefanovski D, Robinson MA, Van Eps A. Effect of a GLP-1 mimetic on the insulin response to oral sugar testing in horses.. BMC Vet Res 2022 Jul 29;18(1):294.
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  2. Pegah A, Abbasi-Oshaghi E, Khodadadi I, Mirzaei F, Tayebinai H. Probiotic and resveratrol normalize GLP-1 levels and oxidative stress in the intestine of diabetic rats.. Metabol Open 2021 Jun;10:100093.
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  3. Fitzgerald DM, Pollitt CC, Walsh DM, Sillence MN, de Laat MA. The effect of different grazing conditions on the insulin and incretin response to the oral glucose test in ponies.. BMC Vet Res 2019 Oct 16;15(1):345.
    doi: 10.1186/s12917-019-2088-1pubmed: 31619223google scholar: lookup
  4. Meier A, de Laat M, Reiche D, Fitzgerald D, Sillence M. The efficacy and safety of velagliflozin over 16 weeks as a treatment for insulin dysregulation in ponies.. BMC Vet Res 2019 Feb 26;15(1):65.
    doi: 10.1186/s12917-019-1811-2pubmed: 30808423google scholar: lookup
  5. de Laat MA, Kheder MH, Pollitt CC, Sillence MN. Sweet taste receptor inhibitors: Potential treatment for equine insulin dysregulation.. PLoS One 2018;13(6):e0200070.
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