01/19/2026
How Does Insulin Cause Laminitis?
By Dr. Kellon on January 18, 2026
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.
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 http://www.ncbi.nlm.nih.gov/pubmed/20649750d 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
These data suggest that the nuchal ligament depot has unique biological behavior in the horse and is more likely to adopt an inflammatory phenotype than other depots examined. Visceral fat may not contribute to the pathogenesis of obesity-related disorders in the horse as in other species.