Laminitis missing link? Insulin receptors may be the key

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The devastating effect of the detachment of the lamina from the hoof wall is the rotation of the pedal bone.
The devastating effect of the detachment of the lamina from the hoof wall is the rotation of the pedal bone. © University of Melbourne

Veterinary researchers in Australia have identified a possible mechanistic link between high levels of insulin and equine laminitis.

The study, which investigated the effects of insulin on equine hoof lamellar cells in the laboratory, was conducted by the University of Melbourne’s Faculty of Veterinary and Agricultural Science, in conjunction with the Waltham Equine Studies Group, which underpins the science behind the Spillers horse feed brand. It has recently been published in the research journal PeerJ.

High levels of the hormone insulin have been known for some time to cause acute endocrine laminitis – this is the most common form of the condition, seen when ponies and certain types of horses graze lush pasture or consume a starch or sugar-rich diet, or when they develop PPID (pituitary pars intermedia dysfunction, also known as Cushing’s syndrome).

When ponies and certain types of horses graze lush pasture or consume a starch or sugar-rich diet, high levels of the hormone insulin can cause acute endocrine laminitis
When ponies and certain types of horses graze lush pasture or consume a starch or sugar-rich diet, or when they develop PPID © Spillers

Many ponies and horses at risk of the condition produce large spikes of insulin in their blood stream after consuming meals high in non-structural carbohydrates (in particular starch and simple sugars) which indicates that this could be the way in which they succumb to acute endocrine laminitis.

The mechanism by which insulin, a metabolic hormone known best for its role clearing glucose from the blood stream, can cause effects in the foot leading to laminitis has been the subject of much debate in recent years. Hormones such as insulin must interact with a specific receptor on the surface of cells in order to produce their effects. What has confused researchers in the past is that there appear to be no insulin receptors on the hoof lamellar cells (these cells give the lamellar tissues their strength and changes to their growth or structure weaken the bonds and cause laminitis).

The researchers considered the close similarities between insulin and a growth factor hormone called insulin-like growth factor -1 (IGF-1). There are receptors for IGF-1 on the lamellar cells, and the researchers speculated that high concentrations of insulin might be able to cross-stimulate these cells by activating the IGF-1 receptors. To investigate this possibility PhD student Courtnay Baskerville, together with her supervisor Professor Simon Bailey, developed a method for culturing lamellar epithelial cells in the laboratory, and incubated them with increasing concentrations of insulin.

They found that high concentrations of insulin stimulated the cells to proliferate. Furthermore, this effect could be prevented using an antibody that specifically blocks only the IGF-1 receptor. Further downstream effects within the cells were also shown. The changes seemed to occur mainly at very high concentrations of insulin. Similar concentration levels can be seen in ponies and horses with insulin dysregulation linked to Equine Metabolic Syndrome, but are not commonly seen in normal horses who are considered to be at lower risk of laminitis.

Simon Bailey is a Professor of Pre-clinical Veterinary Sciences at the Melbourne Veterinary School, University of Melbourne. © University of Melbourne
Professor Simon Bailey. © University of Melbourne

Further work is under way to determine exactly how these cellular changes induced by sustained high insulin concentrations might cause laminitis. However, it seems that targeting the IGF-1 receptor may be an option for developing new drugs to prevent and treat laminitis.

Professor Simon Bailey said: “The information gathered in this study provides the equine industry worldwide with valuable insights into the causes of the common and serious condition of laminitis. The research group would like to acknowledge the support of the Waltham Centre for Pet Nutrition, in particular the involvement of Professor Pat Harris.”

 The effect of insulin on equine lamellar basal epithelial cells mediated by the insulin-like growth factor-1 receptor. Baskerville C.L., Chockalingham, S., Harris, P.A., Bailey S.R. (2018). PeerJ 6:e5945  (DOI 10.7717/peerj.5945).

One thought on “Laminitis missing link? Insulin receptors may be the key

  • February 6, 2019 at 3:28 pm
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    A medication to help these horses cannot come soon enough.
    I have a mare that suffers with metabolic founder, the only year she didn’t was when she was in foal. I give her a toxin binder in her feed which seems to help her

    Reply

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