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PloS one2018; 13(6); e0200070; doi: 10.1371/journal.pone.0200070

Sweet taste receptor inhibitors: Potential treatment for equine insulin dysregulation.

Abstract: Hyperinsulinemia is a major risk factor for equine laminitis, a debilitating and painful foot condition. Sweet taste receptor (T1R2/3) inhibitors have been used to reduce the insulin and glucose responses to oral carbohydrates in other species. However, their effect in horses has not been investigated. It would be useful to be able to attenuate the large post-prandial insulin response that typically occurs when a carbohydrate-rich meal is fed to insulin-dysregulated horses. Here we have determined the efficacy of two T1R2/3 inhibitors, lactisole and Gymnema sylvestre, for reducing glucose uptake by the equine small intestine in vitro; and post-prandial insulin secretion in ponies in vivo, following a carbohydrate-based meal. We used gas chromatography-mass spectrometry to measure 2-deoxyglucose uptake by explants of small intestine, in the presence and absence of the T1R2/3 inhibitors. Lactisole and G sylvestre reduced 2-deoxyglucose uptake by the intestinal explants by 63% (P = 0.032) and 73% (P = 0.047), respectively, compared to control samples. The study in vivo investigated the effect of the inhibitors on the blood glucose and serum insulin responses to a meal containing D-glucose. Three doses of each inhibitor were tested using a Latin square design, and each dose was compared to a meal with no inhibitor added. Lactisole had no effect on glucose and insulin concentrations, whereas G sylvestre was partially effective at reducing post-prandial blood glucose (by ~10%) and serum insulin concentrations (~25%) in seven ponies, with a most effective dose of 10 mg/kg bodyweight. These data provide preliminary support that T1R2/3 inhibitors may be a useful therapeutic strategy for the management of equine insulin dysregulation and the prevention of laminitis. However, further optimisation of the dose and delivery method for these compounds is required, as well as a direct investigation of their activity on the equine sweet taste receptor.
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Publication Date: 2018-06-29 PubMed ID: 29958298PubMed Central: PMC6025858DOI: 10.1371/journal.pone.0200070Google 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 researchers studied the effects of sweet taste receptor inhibitors in horses to combat insulin imbalance associated with high-carb meals, a key risk factor for equine laminitis. The two inhibitors in focus were lactisole and Gymnema sylvestre, known to reduce insulin and glucose responses. Results demonstrated the partial effectiveness of G. sylvestre in lowering post-meal blood glucose and insulin levels, while lactisole had no significant effect.

Research Methodology

  • The efficacy of the sweet taste receptor inhibitors lactisole and Gymnema sylvestre in cutting glucose absorption by the equine small intestine was investigated through in vitro analysis.
  • Post-meal insulin secretion was also examined following a carbohydrate-based diet in vivo in ponies.
  • Gas chromatography-mass spectrometry was used to measure 2-deoxyglucose intake by small intestine samples, both with and without the addition of the inhibitors.
  • In the in vivo study, the blood glucose and serum insulin responses to a meal containing D-glucose were measured. Three dose levels of each inhibitor were trialled using a Latin square design, with each dose compared against a meal with no inhibitor.

Key Findings

  • Both lactisole and Gymnema sylvestre have been shown to reduce 2-deoxyglucose uptake by the intestinal samples by 63% and 73% respectively.
  • In the in vivo study, G. sylvestre worked to lower post-meal blood glucose levels by around 10% and serum insulin levels by 25% in the tested ponies. The optimum dosage of G. sylvestre proposed by the study was 10 mg/kg body weight.
  • Lactisole, on the other hand, showed no significant impact on glucose and insulin levels in the ponies.

Conclusions and Suggestions for Further Research

  • The research has marked potential for using T1R2/3 inhibitors to manage equine insulin dysregulation and prevent laminitis, with preliminary support for G. sylvestre specifically.
  • However, further fine-tuning of the dosage and administering method for the respective compounds is required for stretchier effectiveness.
  • Moreover, direct research investigating the inhibitors’ activity on the equine sweet taste receptor is also recommended to further understand and optimize their potential benefits.

Cite This Article

APA
de Laat MA, Kheder MH, Pollitt CC, Sillence MN. (2018). Sweet taste receptor inhibitors: Potential treatment for equine insulin dysregulation. PLoS One, 13(6), e0200070. https://doi.org/10.1371/journal.pone.0200070

Publication

PloS one
ISSN: 1932-6203
NlmUniqueID: 101285081
Country: United States
Language: English
Volume: 13
Issue: 6
Pages: e0200070
PII: e0200070

Researcher Affiliations

de Laat, Melody Anne
  • School of Earth, Environmental and Biological Sciences, Queensland University of Technology, Brisbane, Queensland, Australia.
Kheder, Murad Hasan
  • School of Earth, Environmental and Biological Sciences, Queensland University of Technology, Brisbane, Queensland, Australia.
Pollitt, Christopher Charles
  • School of Veterinary Science, The University of Queensland, Gatton, Queensland, Australia.
Sillence, Martin Nicholas
  • School of Earth, Environmental and Biological Sciences, Queensland University of Technology, Brisbane, Queensland, Australia.

MeSH Terms

  • Animals
  • Benzene Derivatives / pharmacology
  • Gymnema sylvestre
  • Horse Diseases / blood
  • Horse Diseases / drug therapy
  • Horses
  • Hyperinsulinism / blood
  • Hyperinsulinism / drug therapy
  • Hyperinsulinism / veterinary
  • Insulin / blood
  • Intestinal Absorption / drug effects
  • Intestine, Small / metabolism
  • Receptors, G-Protein-Coupled / antagonists & inhibitors
  • Receptors, G-Protein-Coupled / metabolism

Conflict of Interest Statement

The authors have declared that no competing interests exist.

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Citations

This article has been cited 2 times.
  1. Durham AE, Frank N, McGowan CM, Menzies-Gow NJ, Roelfsema E, Vervuert I, Feige K, Fey K. ECEIM consensus statement on equine metabolic syndrome. J Vet Intern Med 2019 Mar;33(2):335-349.
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  2. Smith L, Moran AW, Al-Rammahi M, Daly K, Shirazi-Beechey SP. Determination of sweetener specificity of horse gut-expressed sweet taste receptor T1R2-T1R3 and its significance for energy provision and hydration. Front Vet Sci 2024;11:1325135.
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