PeerJ2018; 6; e5945; doi: 10.7717/peerj.5945

The effect of insulin on equine lamellar basal epithelial cells mediated by the insulin-like growth factor-1 receptor.

Abstract: In horses and ponies, insulin dysregulation leading to hyperinsulinemia may be associated with increased risk of laminitis, and prolonged infusion of insulin can induce the condition. It is unclear whether insulin may have a direct or indirect effect on the lamellar tissues. Insulin is structurally related to insulin-like growth factor (IGF-1), and can bind the IGF-1 receptor, albeit at a lower affinity than IGF-1. Methods: Immunohistochemistry was performed on formalin-fixed lamellar tissue sections from six normal horses, euthanised for non-research purposes, using an anti-IGF-1 receptor antibody. In further studies, lamellar epithelial cells were obtained by collagenase digestion from the hooves of 18 normal horses, also euthanised for non-research purposes, and incubated for 48 h in the presence of insulin (0-2,000 m IU/ml). The increase in cell numbers was determined using a cell proliferation assay, and compared to the effect of zero insulin using one-way ANOVA. Results: Immunohistochemistry demonstrated IGF-1 receptors on lamellar epidermal epithelial cells. With cultured cells, insulin caused a concentration-dependent increase in cell proliferation compared to untreated cells (maximal effect 63.3 ± 12.8% more cells after 48 h with 1,000 m IU/ml insulin; < 0.01). Co-incubation with a blocking antibody against the IGF-1 receptor significantly inhibited the proliferative effect of insulin ( < 0.01). Conclusions: These results demonstrate that IGF-1 receptors are present on lamellar epithelial cells. At high physiological concentrations, insulin may activate these cells, by a mechanism involving IGF-1 receptors, resulting in a proliferative effect. This mechanism could help to explain the link between hyperinsulinemia and laminitis.
Publication Date: 2018-11-29 PubMed ID: 30519508PubMed Central: PMC6275117DOI: 10.7717/peerj.5945Google Scholar: Lookup
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  • Journal Article

Summary

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This research investigates the relationship between insulin and laminitis in horses, suggesting that high levels of insulin could promote proliferation of lamellar epithelial cells via insulin-like growth factor-1 (IGF-1) receptors.

Methods

  • The study started with immunohistochemistry applied on formalin-fixed lamellar tissue sections from six horses, using an anti-IGF-1 receptor antibody. This step was necessary to reveal IGF-1 receptors on lamellar cells.
  • In the next phase, lamellar epithelial cells were harvested from 18 healthy horses and incubated for 48 hours in varying concentrations of insulin. This aimed at investigating the effect of insulin on the increase in cell numbers using a cell proliferation assay. The results were then compared with those of cells that had no insulin exposure.

Results

  • Immunohistochemistry confirmed the presence of IGF-1 receptors on lamellar epidermal epithelial cells.
  • When exposed to insulin in culture, a significant increase in cell proliferation was noticed compared to untreated cells. The maximal effect showed a 63.3 ± 12.8% increase in cells after 48 hours with 1,000 m IU/ml insulin.
  • The inclusion of a blocking antibody against the IGF-1 receptor was able to significantly inhibit insulin’s proliferative effect.

Conclusions

  • The findings confirmed the presence of IGF-1 receptors on lamellar epithelial cells.
  • The research showed that, at high physiological concentrations, insulin could activate these cells via IGF-1 receptors, causing a proliferative effect.
  • This process may explain the potential link between hyperinsulinemia (a condition characterized by excessive levels of insulin in the blood) and laminitis, a painful disease affecting horse’s hooves.

Cite This Article

APA
Baskerville CL, Chockalingham S, Harris PA, Bailey SR. (2018). The effect of insulin on equine lamellar basal epithelial cells mediated by the insulin-like growth factor-1 receptor. PeerJ, 6, e5945. https://doi.org/10.7717/peerj.5945

Publication

ISSN: 2167-8359
NlmUniqueID: 101603425
Country: United States
Language: English
Volume: 6
Pages: e5945
PII: e5945

Researcher Affiliations

Baskerville, Courtnay L
  • Faculty of Veterinary and Agricultural Sciences, University of Melbourne, Melbourne, VIC, Australia.
Chockalingham, Subu
  • Faculty of Veterinary and Agricultural Sciences, University of Melbourne, Melbourne, VIC, Australia.
Harris, Patricia A
  • Equine Studies Group, WALTHAM Centre for Pet Nutrition, Melton Mowbray, Leicestershire, UK.
Bailey, Simon R
  • Faculty of Veterinary and Agricultural Sciences, University of Melbourne, Melbourne, VIC, Australia.

Conflict of Interest Statement

The authors declare that they have no competing interests.

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Citations

This article has been cited 4 times.
  1. Li Z, Wang S, Zhao H, Yan P, Yuan H, Zhao M, Wan R, Yu G, Wang L. Artificial neural network identified the significant genes to distinguish Idiopathic pulmonary fibrosis.. Sci Rep 2023 Jan 21;13(1):1225.
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