Journal
DOMESTIC ANIMAL ENDOCRINOLOGY
Volume 66, Issue -, Pages 21-26Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.domaniend.2018.05.008
Keywords
Horses; Hyperinsulinemia; IGF-1; Insulin; Laminitis; Receptors
Funding
- MARS Petcare
- Queensland University of Technology
- Australian Research Council
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Although it is well established that equine laminitis can be triggered by extreme hyperinsulinemia, the mechanism of insulin action is not known. High concentrations of insulin lead to separation of the weight-bearing apparatus from the hoof wall and are associated with an increased cycle of cell death and proliferation in the lamellae. Gene expression and immunohistochemistry studies have indicated that the lamellae are sparsely populated with insulin receptors, whereas IGF-1 receptors (IGF-1R) are abundant, suggesting that the action of insulin may be mediated by insulin binding to the IGF-1R. To investigate this possibility, cell membrane fragments containing IGF-1R were extracted from the livers of 6 horses and the lamellae of >50 horses euthanized for non-research purposes at an abattoir. Radioligand-binding studies using I-125-IGF-1 and I-125-insulin confirmed an abundance of high-affinity IGF-1R in the liver (K-D 0.11 nM, B-max 223 fmol/mg protein) and lamellae (K-D 0.16 nM, B-max 243 fmol/mg protein). However, the affinity of insulin for binding to the lamellar IGF-1R (K-i 934 nM) was >5,800 fold less than that of IGF-1, suggesting that insulin is unlikely to bind to equine IGF-1R at physiological concentrations. Although insulin receptors could be detected in the liver (K-D 0.48 nM, B-max 123 fmolimg protein), they were barely detectable in lamellae (estimated B-max 14 fmol/mg protein). There was no evidence to support the presence of insulin/IGF-1 hybrid receptors in either tissue. These findings suggest that insulin does not act directly through IGF-1 receptors and that an alternative theory is required to explain the mechanism of insulin action in laminitis. (C) 2018 Elsevier Inc. All rights reserved.
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