Sunday, September 30, 2012

Laminitis Research: Where Does Your Money Go? Animal Health Foundation Funds Melody de Laat’s Study of Insulin-Like Receptors in the Horse’s Foot

It’s a long, long way from Queensland, Australia to Stillwater, Oklahoma. The University of Queensland had palm trees and kangaroos. Oklahoma State has pickup trucks and cowboy hats.
 
What could  uproot a young woman and move her halfway around the world?

 
Two words: Laminitis research.


Melody de Laat was a rising star back in Queensland. She earned a PhD as part of the world-renowned Australian Equine Laminitis Research Unit. Director Chris Pollitt, BVSC, PhD instilled in her the curiosity and the drive to earn not just a doctorate, but a place in the small but significant legion of successful laminitis researchers scattered around the world. 
 
Working with Dr. Pollitt, Melody discovered that receptors designed to receive insulin-like growth factor 1 (IGF-1) may be binding to insulin instead in horses when horses have high levels of insulin.

This groundbreaking discovery may enable scientists to develop strategies to try to block IGF-1 receptors from receiving insulin and prevent the disease from occurring.

The equine foot is very dependent on glucose for metabolism, but it is not dependent on insulin to deliver that glucose. Horses have a large number of IGF-1 receptors in their feet, but no insulin receptors. Pollitt’s team theorizes that these IGF-1 receptors are being stimulated by insulin that mimics insulin-like growth factor 1 and is binding to these receptors.

When this happens, the lamina stretch, and laminitis occurs.

To continue her research, Melody accepted a post-doctoral position at Oklahoma State University College of Veterinary Medicine. Even though she has only been there a few months, she’s hard at work.



Before Melody left Australia, she accepted a challenge to explain her PhD research in plain English to an audience who knew nothing about laminitis or horses--in three minutes.

Melody’s research at Oklahoma State is funded by your donations through the Animal Health Foundation. Will her research make a difference to horses at risk for laminitis? The Animal Health Foundation believes it will. 

Here’s a brief description of the project we are funding,  with your help:
Investigation of the regulation of glucose transport and insulin signaling pathways in the insulin-induction model of laminitis
Problems associated with abnormal glucose (i.e. sugar) and insulin processes are of particular interest and concern in horses where a persistently increased level of insulin in the blood causes the development of laminitis. This condition is a relatively common one among many breeds.
The current AHF-funded project being investigated by Drs. Lacombe and de Laat at Oklahoma State University aims to investigate how glucose transport and insulin signaling are regulated in the heart, muscle and lamellar tissues (in the feet) of horses that have laminitis associated with hyperinsulinaemia. 

This will be compared to glucose and insulin regulation in the same tissues of normal horses.

Why is this important research?

1. This project will study tissues that have not been previously examined to assess the pattern of glucose metabolism during very high blood insulin levels. 

2. The work will build on the limited available data on lamellar metabolism in horses with insulin-associated laminitis by investigating new topics such as intracellular signaling and inflammatory pathways in the foot and how they relate to glucose transport.

3. Characterization of the changes in glucose transport during conditions of high insulin will provide new insights into the mechanisms of insulin resistance in horses and may facilitate the development of novel therapeutic interventions for the management of metabolic diseases in horses. 

4. Finally, better understanding of the insulin-signaling processes in the foot during increased insulin availability will improve our overall understanding of laminitis. 
This may lead to new avenues for disease treatment and prevention.  

The Animal Health Foundation is encouraged by Melody’s continued involvement in laminitis research, and in her move to the United States. We are confident that her research will yield results that will move our efforts forward and ever closer to our goal of ending this terrible disease.

Thank you for your support of the Animal Health Foundation’s laminitis research.


Thursday, September 13, 2012

Equine Endocrinology Summit: The Animal Health Foundation's Laminitis Research Connection

Is laminitis research just a jumble of complicated words? Dr. Walsh helps us find out why research into equine endocrine problems is critical to understanding why, how, when and if horses get laminitis.


Dr. Don Walsh
The Animal Health Foundation's Dr Don Walsh has answered some questions about The 2012 Equine Endocrinology Summit and how the information presented relates to laminitis research. Some of the speakers at the Summit included AHF-funded researchers Melody De Laat from Oklahoma State, Nicholas Frank from Tufts and Philip Johnson from the University of Missouri.

AHF: What is The Equine Endocrinology Summit? 

Dr. Walsh: The leading scientific researchers in the field of Equine Metabolic Syndrome (EMS) gathered in Boston on September 7-8 under the direction of Dr. Nicholas Frank, Professor and Chair of the Department of Clinical Sciences in Large Animal Internal Medicine of the Cummings School of Veterinary Medicine at Tufts University. I had the privilege of attending this meeting, which was sponsored by Boehringer Ingelheim Vetmedica’s Equine Division.

AHF: Why, with all the other conferences, would this meeting be needed? 

Dr. Walsh: We met to discuss the latest research findings and to shape opinion regarding the future research most needed to prevent horses from developing this type of painful laminitis. These gatherings allow for researchers who may have only known someone as a name on a manuscript to meet and interact with each other on a very informal basis. Ideas are exchanged, questions asked, friendships made, and collaborations often occur.

AHF: Did you talk only about metabolic problems? What about laminitis?

Dr. Walsh: Although Equine Metabolic Syndrome (EMS) was the main subject, some time was delegated to hearing the latest information regarding PPID (Cushing’s Disease). Both conditions are extremely relevant to laminitis, since so many affected horses develop laminitis. To understand this type of laminitis, research is exploring endocrine processes that can initiate laminitis. While EMS and PPID were the area of great interest this year, the Summit previously also covered other endocrine disorders.

AHF: What does this group hope to achieve? 

Dr. Walsh: The general direction and driving goal of the group is to find ways to diagnose both EMS and PPID earlier, before horses develop the crippling disease laminitis.

AHF: What was this meeting's most important new development relevant to the Animal Health Foundation's interest in laminitis research? 

Dr. Walsh: One of the most widely agreed upon ideas, regarding a diagnosis of EMS, was the use of an oral sugar test to reveal an abnormally large insulin and or glucose response seen in the blood measured 75 minutes after an oral dose of sugar is given. Those horses and ponies that test positive are at high risk of developing laminitis and will require special husbandry practices and in some cases drugs to maintain normal levels of insulin and normal feet. AHF is integrally involved in this research project (see upcoming article) with Dr. Nick Frank at Tufts University.

AHF: What does this mean to our horses that are at risk for EMS-type laminitis? 

Dr. Walsh: I can imagine that, in the near future, we might include an oral sugar test as part of the annual physical exam. It might work like this: the owner gives the horse two ounces of common household Karo syrup before the veterinarian arrives. Then the veterinarian takes a blood sample 75 minutes later to test the insulin and glucose levels. If the horse has any symptoms of PPID (Cushing’s Disease), a test for ACTH can also be done.

AHF: How does that relate to laminitis? 

Dr. Walsh: We know that both EMS and PPID can result in laminitis. The changes start to occur when insulin levels are elevated for a prolonged time, causing alterations in the growth pattern of the foot. This results in abnormal rings on the external hoof capsule and a separation in the hoof wall at the toe, when seen from the bottom of the foot. Early recognition and correction of the insulin level is essential to prevent laminitis. 

AHF: Did you have a favorite personal experience? 

Dr. Walsh: One of the highlights of the conference for me was meeting and enjoying a good visit with Dr. Jill Beech, who is now retired from University of Pennsylvania’s New Bolton Center. Her wisdom and experience and plain good common sense was demonstrated by her participation in many discussions during the meeting. Getting to spend some time with this great researcher was very inspiring to me. There was great planning and organization and running of the program by Dr. Nick Frank.

Resources:
Read the American College of Veterinary Internal Medicine (ACVIM) Consensus Statement on Equine Metabolic Syndrome, published in 2010 and co-authored by Dr. Frank.

Watch the Animal Health Foundation's short video on how Equine Metabolic Syndrome and Cushing's Disease (PPID) are related to laminitis.

Note: Text and images © Animal Health Foundation, 2012. All rights reserved. No reproduction without permission.