The effect of diet on hormone levels in horses and ponies and in vitro effects of insulin on lamellar tissue

Abstract

Equine laminitis is a multifactorial condition leading to the rotation of the distal phalanx. It is widely accepted that endocrinopathic is the most common form of the condition and that Equine Metabolic Syndrome (EMS) is a common predisposing factor associated with laminitis, of which, the pony is often more susceptible than the horse. Recent studies have shown that hyperinsulinaemia plays a significant role in the development of endocrinopathic laminitis, however the direct causal link between hyperinsulinaemia and laminitis is still not fully understood. The aim of the studies presented in this thesis aimed to further investigate this link and to determine what other factors may contribute to hyperinsulinaemia in the horse.

The in vitro studies presented in this thesis have shown that as the concentration of insulin increases, so does the rate of cellular proliferation of the equine lamellar epithelial cells. It was shown that whilst there are no insulin receptors present at the site of the pathological lesions associated with laminitis, the insulin-like growth factor-1 (IGF-1) receptor (IGF-1R) is present. And due to the structural similarities between IGF-1 and insulin, insulin can act on the IGF-1R causing similar cellular cascades mediated through the ERK 1/2 pathway, namely proliferation. This activity was confirmed through western blotting techniques and also through blocking of the IGF-1R which led to a decrease in the proliferation of lamellar epithelial cells.

Circulating IGF-1 levels were also measured in three different equine breeds, two of which have been shown in the past to be predisposed to the development of EMS, the pony and the Andalusian horse, as well as the particularly insulin sensitive Standardbred horse. The levels of IGF-1 were measured during periods of obesity and weight and whilst it was shown that ponies had higher IGF-1 concentrations than Standardbreds, there was no significant difference in IGF-1 concentration between the Andalusian and Standardbred. This suggests that not all breeds of horse predisposed to endocrinopathic laminitis will have increased IGF-1 concentrations and thus, circulating IGF-1 may not play a significant role in the development of endocrinopathic laminitis.

Finally, the studies presented in this thesis have shown that the enteroinsular axis may be an important mechanism to consider in the development of hyperinsulinaemia. The studies presented in this thesis show that GIP did not correlate strongly with insulin release, however previous studies by our group found that GLP-1 did. Further to these findings, the studies of this thesis, that localise the incretin releasing L and K cells in the intestinal tract of horses, suggest that incretin release and thus, insulin release may be heightened in response to NSCs digestion, the fermentation of fructans and/or volatile fatty acid increases.