Sunday, October 13, 2013

Equine Incretins in Laminitis Research: Animal Health Foundation Leads the Way in New Investigations into Equine Insulin Resistance



On September 24, the Animal Health Foundation Board of Directors announced a $70,000 grant to Professor Martin Sillence of the Queensland University of Technology (QUT) in Australia to study a new phase of the insulin resistance process at the root of “metabolic” or endocrine-related laminitis in horses.

Remember this word: incretins. Pronounced “in-CREE-tinz”, this funny little word will be one that you will be hearing often in months to come. 

Professor Martin Sillence of
Queensland University of

Technology
Incretins are tiny peptides produced in the small intestine in response to eating sugar. They travel via the bloodstream to the pancreas to stimulate increased production of insulin. This is the basis for the Animal Health Foundation’s previous research to develop a simple “Oral Sugar Test”: horses that are prone to develop laminitis have a higher insulin response after a dose of oral sugar.

To understand this new direction in AHF research, Donald M. Walsh, DVM, president and founder of the organization, answered some questions about incretins and the possible benefits of funding research that does not, at first glance, seem to be about horses with laminitis.

1. AHF Question: What’s the overall direction for future laminitis research funding from the AHF?

Dr. Walsh: Endocrinopathic laminitis is responsible for the vast majority of laminitis in this country. As we follow the lead of human insulin research, AHF finds the field of incretin research very interesting and worth investment of research money. Very little is known about incretins in horses and what role they are playing in the control of insulin and in glucose metabolism.


When we hear “laminitis”, we think “feet”, but we have to consider how the damaging agents are reaching the feet, and what organs or body systems may be creating them.


2. AHF Question: Hang on a minute. What are incretins, again? 

Dr. Walsh: Incretins are small proteins that are produced by cells in the intestine in response to the consumption of carbohydrates (sugar). The incretins then travel by the blood to their target organ, the pancreas. At the pancreas, they enhance the production of insulin. Studying how this pathway controls insulin levels may lead to strategies that can prevent the common form of metabolic laminitis.


3. AHF Question: Laminitis research means researching the pancreas? That’s a long way from the hoof.

Dr. Walsh: We know that high levels of insulin can cause laminitis. The pancreas is the only location in the body that produces insulin. Insulin is a hormone, a substance produced by the body and excreted into the bloodstream to be delivered to its target tissue.

In the case of insulin, it affects the delivery of glucose into the cells; glucose, of course, provides the energy required to maintain normal health of the cell. In the horse, excess levels of insulin lead to damage to the lamina’s basement membrane, resulting in the loss of support of the coffin bone; this results in laminitis.




A model of human insulin shows six different colored proteins attached to a central zinc molecule via the amino acid histadine. Incretins have the power to charge the pancreas to create more of this insulin. Excess insulin increases the horse’s danger of developing laminitis as the outward symptom of its underlying metabolic disease. The Animal Health Foundation hopes to learn how the incretins work in a horse, and find a way to interrupt the pathway and thereby control an at-risk horse’s chances of developing laminitis. (image courtesy of Wellcome Images library)


4. AHF Question: Why not just study research on incretins in humans, that must have already been done?

Dr. Walsh: In human type 2 diabetes, the pancreas fails (finally) to produce insulin; this is not a problem for the horse. So in human medicine, they are developing drugs that act like incretins to cause the failing pancreas to produce more insulin. If incretins work the same way in the horse (something we don’t know presently), we will be trying to find ways to down-regulate incretin production to reduce insulin production by the pancreas, thereby lowering blood insulin levels and eliminating the negative effect of excess insulin on the laminae (laminitis)

Donald M. Walsh, DVM is
president and founder of the
Animal Health Foundation

So we do follow the lead of human research, but horses and people can be quite different. All mammals share some metabolic pathways but their regulation by hormones like incretins can be quite different and require species-specific research to understand their physiology.

A good example of this is the horse’s ability to continue to produce large amounts of insulin via the pancreas whereas the human pancreas becomes deficient and diabetes results, requiring insulin injections to maintain health.

5. Where is AHF’s equine incretin research going on? Who is/are the researcher(s)?


Dr. Walsh: AHF is funding some work presently being done by Dr. Nick Frank at Tufts University in Massachusetts, and also a larger study at Queensland University of Technology (QUT) in Brisbane, Australia. This is headed by Dr. Martin Sillence. Both of these men are accomplished laminitis researchers who have made significant contributions to our knowledge of laminitis.

6. What would be the ideal outcome of the AHF equine incretin research?
 

Dr. Walsh: After we understand how incretins are working in the horse, the ideal outcome would be to develop laminitis prevention strategies based on controlling the production of insulin by regulating the incretin response to eating carbohydrates. If we can control insulin levels in the horse, we can prevent this common form of laminitis.

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About AHF: The Animal Health Foundation is a 501 (c) (3) all-volunteer non-profit organization dedicated solely to identifying and funding critical research into the disease of laminitis in horses. 


Until recent years, excess insulin was not considered a health problem in horses, and it has only been recently that insulin was found to play the key role in the common low-grade "metabolic" form of laminitis. The Animal Health Foundation has taken a leadership role in funding research on this form of laminitis, primarily at the Australian Equine Laminitis Research Unit at the University of Queensland.

AHF can only continue to function as the leader in laminitis research funding with your help. AHF puts together donations large and small from horse owners, veterinarians, farriers, and any individual who wants to make a difference in beating this terrible disease in horses.

Throughout this website, you will see sidebar “donation” buttons that will lead you to the AHF donor page where you can make a one-time or recurring pledge to be part of the AHF’s research efforts. The postal address is also given if you would prefer to send a check. 


Visit the “donate” page for full details or email info@ahf-laminitis.org for personal assistance with your donation.

Article, photos and website contents © Animal Health Foundation. All rights reserved. No reproduction in any form without permission.

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