Effects of insulin on IGF-1 receptors in equine lamellar tissue in vitro.
Abstract: Although it is understood that equine endocrinopathic laminitis can be triggered by high concentrations of insulin, it is unclear whether this represents a direct action on lamellar tissue via insulin receptors (InsR), an interaction with IGF-1 receptors (IGF-1R), or some other, indirect action. This uncertainty is because of the reported scarcity of InsR in lamellar tissue and the low affinity of insulin for equine IGF-1R. In the present study, the effects of insulin and IGF-1 (as a positive control) were examined using lamellar explants isolated from the hooves of healthy horses and incubated in cell culture medium for between 2 min and 48 h. In this system, a low physiological concentration of IGF-1 (10 nM; 1.31 ng/mL) caused a marked increase in the appearance of phosphorylated IGF-1R after 5 min (P < 0.05), and this effect was blocked by a human anti-IGF-1R monoclonal antibody (mAb). However, a high concentration of insulin (10 nM; 1,430 μIU/mL) appeared to cause dephosphorylation of the IGF-1R after 5 min (P < 0.01), 15 min, and 30 min (P < 0.001). Using H-thymidine as a marker, it was also demonstrated that insulin and IGF-1-stimulated cell proliferation in lamellar explants over the same concentration range as each other (1-100 nM), implying that each peptide acts via its own receptor (P < 0.001). Conversely, the effect of both peptides could be blocked using a selective anti-IGF-1R mAb (P < 0.001), implying that insulin acts via IGF1-R (either directly or indirectly). Notwithstanding this conundrum, the results demonstrate that insulin acts directly on lamellar tissue and suggest that a therapeutic anti-IGF-1R mAb could be useful in treating or preventing endocrinopathic laminitis.
Copyright © 2020 Elsevier Inc. All rights reserved.
Publication Date: 2020-07-29 PubMed ID: 32818904DOI: 10.1016/j.domaniend.2020.106530Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research investigates the role of insulin in triggering equine endocrinopathic laminitis, a condition affecting horses, through interactions with insulin receptors and IGF-1 receptors found in the hoof tissue of horses.
Overview of the Research
- The study set out to understand the mechanisms by which high concentrations of insulin can trigger a condition in horses known as equine endocrinopathic laminitis. This condition is associated with severe lameness and pain experienced by affected horses, often resulting in reduced welfare and performance.
- The researchers aimed to clarify whether this process involves direct action via insulin receptors located in the hoof tissue (known as lamellar tissue), interaction with another type of receptors called IGF-1 receptors, or through some other indirect action.
Study Design and Methods
- The researchers took lamellar tissue samples from healthy horses and cultured them in a lab, followed by exposure to different concentrations of insulin and IGF-1 for varied periods ranging from 2 minutes to 48 hours.
- They also introduced an anti-IGF-1 receptor monoclonal antibody (a lab-created protein that can counter the effects of IGF-1 receptor) to observe the changes.
- Cell proliferation was measured using H-thymidine as an indicator.
Results and Findings
- Results showed that a low physiological concentration of IGF-1 caused a significant increase in the appearance of activated IGF-1 receptors (phosphorylated IGF-1R). This increase was blocked by the human anti-IGF-1R antibody, which indicates the presence and functioning of IGF-1 receptors in the lamellar tissue.
- In contrast, high concentrations of insulin appeared to deactivate the IGF-1 receptors.
- Both insulin and IGF-1 stimulated cell proliferation in the lamellar tissue samples, which could also be blocked with the anti-IGF-1R antibody. The researchers interpret this as an indication that insulin may also act via IGF1 receptors.
Conclusions and Implications
- The results suggest that insulin directly impacts lamellar tissue, although the exact mechanisms remain unclear. It could be that high levels of insulin directly trigger the activation of IGF-1 receptors, leading to laminitis or that insulin acts indirectly through other cellular molecules.
- The study highlights the potential therapeutic use of an anti-IGF-1R monoclonal antibody in the treatment or prevention endocrinopathic laminitis, a promising development for equine health and welfare.
Cite This Article
APA
Rahnama S, Spence R, Vathsangam N, Baskerville CL, Bailey SR, de Laat MA, Anderson ST, Pollitt CC, Sillence MN.
(2020).
Effects of insulin on IGF-1 receptors in equine lamellar tissue in vitro.
Domest Anim Endocrinol, 74, 106530.
https://doi.org/10.1016/j.domaniend.2020.106530 Publication
Researcher Affiliations
- School of Biology and Environmental Science, Queensland University of Technology, Brisbane, Queensland, Australia.
- School of Biology and Environmental Science, Queensland University of Technology, Brisbane, Queensland, Australia.
- Department of Veterinary Biosciences, The University of Melbourne, Melbourne, Victoria, Australia.
- Department of Veterinary Biosciences, The University of Melbourne, Melbourne, Victoria, Australia.
- Department of Veterinary Biosciences, The University of Melbourne, Melbourne, Victoria, Australia.
- School of Biology and Environmental Science, Queensland University of Technology, Brisbane, Queensland, Australia.
- School of Biomedical Sciences, The University of Queensland, St Lucia, Queensland, Australia.
- School of Veterinary Science, The University of Queensland, Gatton, Australia.
- School of Biology and Environmental Science, Queensland University of Technology, Brisbane, Queensland, Australia. Electronic address: martin.sillence@qut.edu.au.
MeSH Terms
- Animals
- Antibodies, Monoclonal
- Blotting, Western
- Cell Proliferation
- Gene Expression Regulation / drug effects
- Hoof and Claw / metabolism
- Horses / metabolism
- Insulin / pharmacology
- Receptor, IGF Type 1 / genetics
- Receptor, IGF Type 1 / metabolism
- Tissue Culture Techniques / veterinary
Citations
This article has been cited 1 times.- Rahnama S, Vathsangam N, Spence R, Medina-Torres CE, Pollitt CC, de Laat MA, Bailey SR, Sillence MN. Effects of an anti-IGF-1 receptor monoclonal antibody on laminitis induced by prolonged hyperinsulinaemia in Standardbred horses. PLoS One 2020;15(9):e0239261.
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