How Does Insulin Resistance Cause Laminitis?

It is now widely recognized and accepted that insulin resistance can cause laminitis.  Research has shown that it is the high insulin levels themselves that have this effect, even in normal horses that are experimentally infused with insulin.  The question remaining is how does insulin do this. LAMINITIS CHEST OF BOOKS Drawing from Chest of Books

It has been suggested that high insulin levels cause inflammation and inflammatory cytokine release which then causes laminitis but research on tissue levels so far says no, that’s not the case: http://www.ncbi.nlm.nih.gov/pubmed/24246153 Furthermore, equine obesity and blood insulin levels do not correlate with blood levels of key cytokines called Il-1, Il-6 or TNF-alpha, which are increased in human metabolic syndrome: http://www.ncbi.nlm.nih.gov/pubmed/23216530 Likewise, levels of cytokines in fat depots were no higher in insulin resistant horses than in insulin sensitive ones: http://www.ncbi.nlm.nih.gov/pubmed/20649750 One study did find higher levels of the cytokine TNF-alpha in ponies with a history of prior pasture associated laminitis but seven other markers of inflammation showed no difference compared to ponies that had never had laminitis: http://www.ncbi.nlm.nih.gov/pubmed/19108899

It is known that disorders that cause severe hind gut acidosis and damage, such as overload of grains or chickory root fructan, trigger laminitis by activation of tissue destroying enzymes called matrix metalloproteinases.  That’s not the mechanism with insulin induced laminitis either: http://www.ncbi.nlm.nih.gov/pubmed/21333362

There is one thing linked to IR that might be an important factor.  That is elevated levels of endothelin-1.  Endothelin-1 is a very potent vasoconstrictor.  High insulin exposure also causes increase in receptors for endothelin-1 within the hoof, increased resistance to blood flow, tissue edema and changes in the laminae typical for metabolic laminitis – elongation of the secondary laminae.  The detailed mechanism for the changes in the laminae is not known but the overall situation is similar to a heart attack in the feet. http://www.ncbi.nlm.nih.gov/pubmed/?term=horse+laminitis+endothelin

We have much more to learn but by discarding the mechanisms that do not apply and focusing on the unique changes associated with laminitis in insulin resistance progress will be made in understanding the mechanism and the best way to treat these horses.

Eleanor Kellon, VMD

About Dr. Kellon

Graduate of University of Pennsylvania Veterinary School. Owner of Equine Nutritional Solutions, www.drkellon.com, industry and private nutritional consultations, online nutritional courses. Staff Veterinary Expert at Uckele Health and Nutrition.
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One Response to How Does Insulin Resistance Cause Laminitis?

  1. Billy Blackman says:

    Dr Kellon.
    Last year I read an article indicating that in IR horses that one of the factors on metabolic founder is insulin deprivation to the feet. What do you think of this theory?
    Thanks

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