How Does Insulin Cause Laminitis?

Hooves of horse galloping on a rainy day.
Hooves of horse galloping on a rainy day. Secarter

Newsdate: Tuesday, April 20, 2021 - 8:35 am
Location: TEMPE, Arizona

It is now widely recognized and accepted that Insulin Resistance (IR) 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.

Illustration of horse's foot showing severe laminitis.

Illustration of horse's foot showing severe laminitis

High insulin exposure causes increase in receptors for endothelin-1 within the horse's hoof, increased resistance to blood flow, tissue edema, and changes in the laminae.
© 2020 by JoAnne Rissanen New window.

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: 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:

Likewise, levels of cytokines in fat depots were no higher in IR horses than in insulin-sensitive ones:

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:

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:

There is one thing linked to IR that might be an important factor — 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.

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.

More can be read about endothelin-1 in Dr Kellon’s 2013 NO Laminitis! Conference Proceeding Endothelin-1: Key Player in Equine Laminitis? and 2017 NO Laminitis! Conference Proceeding  Endocrinopathic Laminitis: How is it Different? Available for free at and on

About ECIR Group Inc

Started in 1999, the ECIR Group is the largest field-trial database for PPID and IR in the world and provides the latest research, diagnosis, and treatment information, in addition to dietary recommendations for horses with these conditions. Even universities do not and cannot compile and follow long term as many in-depth case histories of PPID/IR horses as the ECIR Group.

In 2013 the Equine Cushing's and Insulin Resistance Group Inc., an Arizona nonprofit corporation, was approved as a 501(c)3 public charity. Tax deductible contributions and grants support ongoing research, education, and awareness of Equine Cushing's Disease/PPID and Insulin Resistance.

THE MISSION of the ECIR Group Inc. is to improve the welfare of equines with metabolic disorders via a unique interface between basic research and real-life clinical experience. Prevention of laminitis is the ultimate goal. The ECIR Group serves the scientific community, practicing clinicians, and owners by focusing on investigations most likely to quickly, immediately, and significantly benefit the welfare of the horse.

Press release provided by Nancy Collins - Article by Eleanor M. Kellon, VMD.

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