The equine glucose-dependent insulinotropic polypeptide receptor: A potential therapeutic target for insulin dysregulation.
Abstract: Metabolic disease is a significant problem that causes a range of species-specific comorbidities. Recently, a better understanding of glucose-dependent insulinotropic polypeptide (GIP) biology has led to the suggestion that inhibiting its action may attenuate obesity in several species. In horses, antagonism of GIP may also reduce hyperinsulinemia, which leads to insulin-associated laminitis, a painful comorbidity unique to this species. However, little is known about GIP in horses. The aims of this study were to examine the tissue distribution of equine GIP receptors (eGIPR), to determine whether eGIPR can be blocked using a GIP antagonist not tested previously in horses, and to establish whether there is any association between GIP concentrations and body mass in this species. Archived tissues from healthy horses were used to establish that eGIPR gene expression was strong in pancreas, heart, liver, kidney, and duodenum and absent in gluteal muscle. Pancreatic islets were isolated from fresh horse pancreas using collagenase digestion and layering through a density gradient. Islet viability was confirmed microscopically and by demonstrating that insulin production was stimulated by glucose in a concentration-dependent manner. Insulin release was also shown to be concentration-dependent with GIP up to 0.1µM, and the response to GIP was decreased ( = 0.037) by the antagonist (Pro3)GIP. As for the relationship between body mass and GIP in vivo postprandial GIP concentrations in archived plasma samples were positively correlated with body condition and cresty neck scores ( < 0.05). Thus, the eGIPR is a potential therapeutic target for insulin dysregulation and obesity in horses.
Publication Date: 2017-07-21 PubMed ID: 28727072DOI: 10.2527/jas.2017.1468Google Scholar: Lookup
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- Journal Article
Summary
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This study explores the potential of targeting the equine glucose-dependent insulinotropic polypeptide (GIP) receptor as a treatment for insulin dysfunction and obesity in horses. Researchers examined the tissue distribution of this receptor, assessed the blocking capability of a previously untested GIP antagonist, and investigated the relationship between GIP levels and body mass in horses.
Identification of eGIPR in Various Tissues
- The study utilized tissue samples from healthy horses to identify the presence of the equine GIP receptor (eGIPR). The receptor’s gene expression was notably strong in the heart, liver, pancreas, kidney, and duodenum. Interestingly, it was absent in the horse’s gluteal muscle. This points towards the importance of the GIP receptor in a variety of key bodily functions in horses.
Examination of the Effect of a GIP Antagonist
- Researchers performed experiments using pancreatic islets from horses. The viability of these islets was confirmed using microscopic examination and by demonstrating that insulin production was stimulated by glucose in a concentration-dependent manner.
- Further experiments suggested that the GIP antagonist, (Pro3)GIP, reduces the insulin-releasing response to GIP in a concentration-dependent manner. This novel observation establishes that the GIP receptor in horses can be blocked successfully using a previously untested antagonist, with potential implications for treating metabolic disorders.
Relationship Between GIP Concentrations and Body Mass
- In examining the connection between body mass and GIP levels in horses, the researchers found that postprandial GIP concentrations — those recorded after a meal — showed a positive correlation with body condition as well as cresty neck scores. The study suggests that animals with more mass may have higher GIP levels.
- This association suggests that GIP levels could potentially serve as a useful biomarker for assessing obesity in horses and could inform the development of therapeutic strategies against metabolic syndromes like insulin dysregulation.
Conclusion
- Overall, this study identifies the eGIPR as a potential therapeutic target for insulin dysregulation and obesity in horses. The described results contribute to a better understanding of GIP biology in horses and may pave the way for novel treatment strategies for metabolic disorders in this species.
Cite This Article
APA
Kheder MH, Sillence MN, Bryant LM, de Laat MA.
(2017).
The equine glucose-dependent insulinotropic polypeptide receptor: A potential therapeutic target for insulin dysregulation.
J Anim Sci, 95(6), 2509-2516.
https://doi.org/10.2527/jas.2017.1468 Publication
Researcher Affiliations
MeSH Terms
- Animals
- Duodenum / metabolism
- Female
- Gastric Inhibitory Polypeptide / metabolism
- Glucose / metabolism
- Horses / physiology
- Insulin / metabolism
- Islets of Langerhans / metabolism
- Male
- Obesity / metabolism
- Pancreas / metabolism
- Postprandial Period
- Receptors, Gastrointestinal Hormone / metabolism
Citations
This article has been cited 6 times.- Meier A, McGree J, Klee R, Preuß J, Reiche D, de Laat M, Sillence M. The application of a new laminitis scoring method to model the rate and pattern of improvement from equine endocrinopathic laminitis in a clinical setting. BMC Vet Res 2021 Jan 7;17(1):16.
- 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.
- Moser K, Banse H. Comparison of the glucose and insulin responses of horses to 2 formulations of corn syrup. Can Vet J 2019 Jun;60(6):637-643.
- 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.
- Kheder MH, Bailey SR, Dudley KJ, Sillence MN, de Laat MA. Equine glucagon-like peptide-1 receptor physiology. PeerJ 2018;6:e4316.
- Kemp KL, Skinner JE, Bertin FR. Effect of phenylbutazone administration on the enteroinsular axis in horses with insulin dysregulation. J Vet Intern Med 2025 Jan-Feb;39(1):e17256.
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