BMC veterinary research2018; 14(1); 146; doi: 10.1186/s12917-018-1479-z

Lower plasma trans-4-hydroxyproline and methionine sulfoxide levels are associated with insulin dysregulation in horses.

Abstract: Insulin dysregulation in horses is a metabolic condition defined by high insulin concentrations in the blood and peripheral insulin resistance. This hyperinsulinemia is often associated with severe damage in the hooves, resulting in laminitis. However, we currently lack detailed information regarding the potential involvement of particular metabolic pathways in pathophysiological causes and consequences of equine insulin dysregulation. This study aimed to assess the dynamic metabolic responses given to an oral glucose test (OGT) in insulin-sensitive and insulin-dysregulated horses by a targeted metabolomics approach to identify novel metabolites associated with insulin dysregulation. Results: Oral glucose testing triggered alterations in serum insulin (26.28 ± 4.20 vs. 422.84 ± 88.86 μIU/mL, p < 0.001) and plasma glucose concentrations (5.00 ± 0.08 vs. 9.43 ± 0.44 mmol/L, p < 0.001) comparing basal and stimulated conditions after 180 min. Metabolome analyses indicated OGT-induced changes in short-chain acylcarnitines (6.00 ± 0.53 vs. 3.99 ± 0.23 μmol/L, p < 0.001), long-chain acylcarnitines (0.13 ± 0.004 vs. 0.11 ± 0.002 μmol/L, p < 0.001) and amino acids (2.18 ± 0.11 vs. 1.87 ± 0.08 μmol/L, p < 0.05). Kynurenine concentrations increased (2.88 ± 0.18 vs. 3.50 ± 0.19 μmol/L, p < 0.01), whereas spermidine concentrations decreased during OGT (0.09 ± 0.004 vs. 0.08 ± 0.002 μmol/L, p < 0.01), indicating proinflammatory conditions after oral glucose load. Insulin dysregulation was associated with lower concentrations of trans-4-hydroxyproline (4.41 ± 0.29 vs. 6.37 ± 0.71 μmol/L, p < 0.05) and methionine sulfoxide (0.40 ± 0.06 vs. 0.87 ± 0.13 μmol/L, p < 0.01; mean ± SEM in insulin-dysregulated vs. insulin-sensitive basal samples, respectively), two metabolites which are related to antioxidant defense mechanisms. Conclusions: Oral glucose application during OGT resulted in profound metabolic and proinflammatory changes in horses. Furthermore, insulin dysregulation was predicted in basal samples (without OGT) by pathways associated with trans-4-hydroxyproline and methionine sulfoxide, suggesting that oxidative stress and oxidant-antioxidant disequilibrium are contributing factors to insulin dysregulation. The present findings provide new hypotheses for future research to better understand the underlying pathophysiology of insulin dysregulation in horses.
Publication Date: 2018-05-02 PubMed ID: 29716602PubMed Central: PMC5930486DOI: 10.1186/s12917-018-1479-zGoogle Scholar: Lookup
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  • Journal Article

Summary

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The research paper explores the connection between lower levels of certain metabolites, particularly trans-4-hydroxyproline and methionine sulfoxide, and insulin dysregulation in horses. The findings suggest that oxidative stress and imbalance between oxidants and antioxidants could contribute to insulin dysregulation, offering new areas to explore in future research.

Study Objective and Methodology

  • The research aimed to further understand the metabolic pathways that could be involved in causing insulin dysregulation in horses. This salient condition is characterised by high insulin concentrations in the blood and it often leads to severe hoof damage resulting in laminitis.
  • The researchers subjected insulin-sensitive and insulin-dysregulated horses to an oral glucose test (OGT) and assessed the metabolic responses, with the objective of identifying new metabolites associated with insulin dysregulation.

Results and Findings

  • The oral glucose testing led to significant alterations in serum insulin and plasma glucose concentrations compared to the basal state after 180 minutes. This highlights the sensitivity and dysregulated response of insulin in affected horses.
  • The study also pointed out changes in short-chain acylcarnitines, long-chain acylcarnitines, and amino acids resulting from the OGT.
  • Increased levels of Kynurenine and decreased levels of spermidine were noted during the OGT, suggesting that the oral glucose load induced proinflammatory conditions.
  • What stood out most notably was that insulin dysregulation appeared to be associated with lower concentrations of trans-4-hydroxyproline and methionine sulfoxide, two metabolites related to antioxidant defense mechanisms. This correlation implies that oxidative stress and imbalance in the antioxidant system might be contributory factors to insulin dysregulation in horses.

Conclusions and Implications for Future Research

  • The paper concluded that the application of oral glucose during the OGT instigated marked metabolic and proinflammatory alterations in horses.
  • The correlation between lower trans-4-hydroxyproline and methionine sulfoxide and insulin dysregulation suggests potential pathways and factors to investigate in future research.
  • The implication of oxidative stress and oxidant-antioxidant disequilibrium in insulin dysregulation in horses is a valuable insight, providing a basis for developing further hypotheses and carrying out more detailed studies.

Cite This Article

APA
Kenu00e9z u00c1, Warnken T, Feige K, Huber K. (2018). Lower plasma trans-4-hydroxyproline and methionine sulfoxide levels are associated with insulin dysregulation in horses. BMC Vet Res, 14(1), 146. https://doi.org/10.1186/s12917-018-1479-z

Publication

ISSN: 1746-6148
NlmUniqueID: 101249759
Country: England
Language: English
Volume: 14
Issue: 1
Pages: 146
PII: 146

Researcher Affiliations

Kenu00e9z, u00c1kos
  • Institute of Animal Science, Faculty of Agricultural Sciences, University of Hohenheim, Fruwirthstrau00dfe 35, 70593, Stuttgart, Germany.
  • Present address: College of Veterinary Medicine and Life Sciences, City University of Hong Kong, Kowloon Tong, Hong Kong SAR.
Warnken, Tobias
  • Clinic for Horses, University of Veterinary Medicine Hannover, Foundation, Bu00fcnteweg 9, 30559, Hannover, Germany. tobias.warnken@tiho-hannover.de.
Feige, Karsten
  • Clinic for Horses, University of Veterinary Medicine Hannover, Foundation, Bu00fcnteweg 9, 30559, Hannover, Germany.
Huber, Korinna
  • Institute of Animal Science, Faculty of Agricultural Sciences, University of Hohenheim, Fruwirthstrau00dfe 35, 70593, Stuttgart, Germany.

MeSH Terms

  • Animals
  • Blood Glucose / analysis
  • Glucose Tolerance Test / veterinary
  • Horses / blood
  • Horses / metabolism
  • Hydroxyproline / blood
  • Insulin / blood
  • Insulin Resistance
  • Metabolomics
  • Methionine / analogs & derivatives
  • Methionine / blood

Conflict of Interest Statement

ETHICS APPROVAL AND CONSENT TO PARTICIPATE: Samples from ID horses and ponies were collected during routine diagnostic procedures in the Clinic for Horses, Hannover, and owners gave written informed consent for the study. CONSENT FOR PUBLICATION: Owners gave written informed consent for publication by means of signing our official client acceptance form. COMPETING INTERESTS: The authors declare that they have no competing interests. PUBLISHER’S NOTE: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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