A Closer Look at Insulin
- Apr 1, 2005
When you think of insulin, you might think first of humans and diabetes. But horses have insulin, too, as well as insulin-linked health issues. In fact, this is an area being touched on by researchers in multiple fields, from behavior to laminitis to exercise physiology. In this article, experts share their insights on what's known about insulin, what's under study, and what impact it all has on you and your horse.
What It Is, What It Does
Insulin is a hormone comprised of 51 amino acids. It's produced by the pancreas in response to increased glucose levels in the blood and to changes in certain amino acids, explains Joe Pagan, PhD, president of Kentucky Equine Research (KER) in Versailles, Ky.
Insulin has multiple functions, but in a nutshell, it works to store nutrients from food. To do that, it essentially pulls glucose, fatty acids, and amino acids out of the horse's bloodstream. Thus, it's a key player in the regulation of carbohydrate (glucose), fat, and protein metabolism, explains Ray Geor, DVM, PhD, Dipl. ACVIM, associate professor at the Ontario Veterinary College, University of Guelph, and nutrition consultant for Purina Mills.
Specifically, by working on numerous cells within the body (including liver, muscle, fat, and kidney cells), insulin helps to initiate the following actions:
- Storage of glucose in the form of glycogen, which is the horse's main source of fuel;
- Conversion of fatty acids and glycerol into fat;
- Conversion of amino acids into protein, which is used to build muscle; and
- Prevention of gluconeogenesis, which would cause the liver and kidney cells to make their own glucose.
Focus on Resistance
Of all these tasks, the one currently of most interest to researchers--and ultimately horse owners--is insulin's role in regulating blood glucose concentrations. This is closely linked to ongoing studies of the impact of high-grain diets.
In general, grain is the carbohydrate portion of the horse's diet, containing starches and sugars, which in turn contain glucose. When grain is digested in the horse's small intestine, the glucose is absorbed into the bloodstream, signaling the release of insulin from the pancreas, says Pagan. When everything works properly, the insulin acts on receptor tissues to remove the glucose from the bloodstream, returning it to a normal concentration.
What's captured attention lately, though, is the notion of insulin resistance. In this condition, explains Geor, the insulin receptors become less sensitive to the effects of insulin. Therefore the horse becomes less able to deal with glucose entering the body from the digestive tract. Since blood glucose levels remain high, the pancreas continues to produce insulin. This leads to elevated concentrations of insulin in the bloodstream, a condition known as hyperinsulinemia.
Since the glucose remains in the horse's bloodstream, the body cannot make use of the glucose for fuel. So the horse has no energy or is forced to raid its existing fat and muscle stores to produce energy. Eventually, this results in not only loss of weight and muscle, but also exhaustion. As the hypersecretion of insulin continues, the entire process can fail, to the point where the body no longer produces insulin, notes Barry Fitzgerald, PhD, of the University of Kentucky's Gluck Equine Research Center. In the end, the horse ends up with the equivalent of human type-two diabetes.
Equines might be more prone to insulin resistance than other species. Why that's so, and what causes the condition in the first place, are questions for which there are not yet complete answers, says Geor. Genetics might play a role, as it does in humans. (For instance, ponies tend to be more insulin-resistant than horses, says Geor.) Age, too, might decrease the horse's sensitivity to insulin. Obesity almost certainly is a catalyst for the problem, just as it is in humans and other species.
Diet seems to be linked to insulin resistance. As Geor explains, feeding meals high in starch and sugar (i.e., grain) causes large spikes in glucose and insulin levels. Over time, this might lead to insulin resistance.
"More research is needed in this area," he acknowledges. "But there is rationale for reducing or eliminating starch/sugar from the diets of horses with documented insulin resistance. This last point is important, since only a very small proportion of the horse population is insulin-resistant and in need of these dietary changes."
Cushing's disease has also been linked to insulin resistance. "Hyperinsulinemia can be a feature of Cushing's disease and the so-called metabolic syndrome," says Geor. "The hyperinsulinemia has been presumed to be the result of insulin resistance, although scientific evidence is a bit thin in the case of the metabolic syndrome."
A number of factors might cause temporary insulin resistance, notes Fitzgerald. These include inflammation, infection, injury, or even pregnancy and puberty. Time of day might even have an impact, since cortisol--which decreases insulin sensitivity--is usually higher early in the morning vs. evenings.
Tackling the Trouble
Exercise has been shown to be an important management tool for humans dealing with type-two diabetes, says Geor. Likewise, exercise can benefit the insulin-resistant horse by actually increasing the insulin sensitivity of skeletal muscles and fat tissue. Even if you don't see any outward physical changes, a week of daily, 30-minute bouts of low-intensity exercise can improve insulin sensitivity, says Fitzgerald.
It's possible that the mineral chromium will also have a beneficial impact on insulin sensitivity, particularly when paired with exercise. At KER, studies have shown that when exercised horses were fed 5 mg of chromium, they produced less insulin, yet cleared glucose from the blood faster than usual, says Pagan. When repeated with sedentary horses, the chromium supplement had no effect.
Explains Pagan, "Human runners, at high levels of exertion, lose chromium through urinary excretion. We suspect that the 'couch-potato' horses did not have enough loss of chromium to create an effect. Their normal diet provided enough. The hard-working horses were probably losing more chromium, so we saw a beneficial response to adding more." (Pagan notes that the FDA has not approved chromium for use in horses.)
Fitzgerald says research is under way to see if drugs currently used to improve insulin sensitivity in humans might work for horses. His research group at the Gluck Center is also studying methods to modify insulin resistance. In particular, the group's studies focus on the role of fat cells in producing hormones and proteins that directly affect insulin sensitivity.
The Insulin Links
Insulin, and possibly insulin sensitivity, might be tied to several other issues. These include:
Behavior--There's plenty of anecdotal evidence that feeding horses a lot of grain can cause them to become excitable or "hot." Pagan notes that the theory is difficult to prove, because doing controlled behavior research on horses is challenging. Nonetheless, KER completed a study where feeding high-glucose diets did cause excitability in certain horses.
"Insulin is a very powerful hormone," he says. "It affects a bunch of areas. We think, in terms of behavior, it is having a 'knock on' effect (i.e., domino effect) on other hormones that affect behavior."
However, Pagan notes that a horse's behavioral response to elevated glucose and insulin levels varies from one individual to the next. For example, if you fed two horses the same meal, one might have a more notable attitude change than the other. And, adds Pagan, it might not be because the altered horse has responded to the meal by producing higher levels of insulin, but simply that his body is more sensitive to the insulin produced.
"We did one controlled study where it looked like that was the case," he says. "But there hasn't been enough good controlled research on behavior response to say with certainty."
Polysaccharide storage myopathy (PSSM)--Geor says PSSM also appears to be associated with increased insulin sensitivity. The why behind this connection isn't clear, says Geor, but increased sensitivity to insulin might explain why these horses store an abnormal amount of glycogen in skeletal muscle.
Recurrent exertional rhabdomyolysis (RER)--Commonly known as chronic tying-up, RER has been linked to excitement, and because of that, it has a possible link to high insulin levels caused by high-grain diets, says Geor. Pagan notes that KER has teamed with researchers at the University of Minnesota's College of Veterinary Medicine on an RER study that seems to support this theory.
The researchers have found that horses with a genetic susceptibility to RER are sensitive to high levels of glucose in their diets. When fed significant calories from starch, these horses are more likely to experience clinical signs than if those calories come from fat and fermentable fiber (such as hay). The researchers believe that a low-starch diet might be helpful because it's less likely to cause behavioral changes (excitability) that trigger clinical signs.
Laminitis--Insulin-resistant horses appear to be more susceptible to laminitis, even though research hasn't pinned down the exact connection. But, says Geor, "One theory is that the insulin resistance impairs glucose delivery to the laminar cells of the foot, and that this state can trigger cell death and the manifestations of laminitis."
Development--There is some speculation that high levels of insulin in young, growing horses might lead to skeletal disorders, such as developmental orthopedic disorder (DOD) and osteochondrosis dissecans (OCD). In a University of Cambridge study of in-vitro cartilage cells from young, growing horses, cells that were high in insulin did not properly mature and differentiate into bone cells, says Pagan. In addition, he describes a KER study where weanlings fed concentrates that produced high glucose and insulin responses had a higher incidence of skeletal disorders.
The issue is far from resolved, however, with many scientists pointing particularly to the unanswered dilemma of cause and effect. "There have been some associations between the insulin response of foals in relation to the development of DOD," says Fitzgerald. "However, a mechanism has not been put forward for DOD development in such foals. There is also a chicken and the egg question. Did insulin resistance lead to DOD, or did DOD lead to insulin resistance? I have raised this question because insulin resistance will develop under a variety of conditions, (including) surgery, inflammation, hemorrhage, and sepsis. If the DOD foal has an injury or inflammation associated with the development, it may be that insulin resistance subsequently develops."
Management for Now
Another contentious topic right now, says Pagan, is the question of whether elevated levels of insulin can be a problem, even when the system is functioning normally. "Horses didn't evolve to eat the levels of cereal grains that we feed," says Pagan. "In nature, a horse would never see elevated blood glucose and never need elevated insulin. So even though the horse is capable of digesting and storing it as fuel, are there any negatives to feeding meals that produce a high level of glucose? I think, in certain horses, the answer is yes."
Until further research gives us more definitive solutions, the safe bet for now is to avoid feeding meals that cause glucose--and thus insulin--surges. That means lower starch and sugar content, with the emphasis on fiber and, if extra calories and/or energy are needed, added fat. To further optimize insulin sensitivity, keep your horse at a lean, healthy weight and give him plenty of opportunity to exercise. While that's no guarantee that your horse will never suffer from insulin-linked problems, these steps certainly can do no harm and, more likely, will contribute to his overall good health.
BLOOD WILL TELL: Testing for Normal
Blood tests can reveal whether or not your horse's insulin levels are normal. However, it's important to focus on what Pagan calls the normal resting level--that is, the insulin levels after glucose has been stored, not the level produced in response to a meal. For this reason, your vet should take the blood sample at least four hours after a meal that included grain. Since multiple other factors can also play a role in insulin levels, don't hesitate to ask your vet for follow-up diagnostics if the first test results are abnormal. Before making any dramatic dietary changes or beginning medication, you want to be sure there's a real problem with your horse.--Sushil Dulai Wenholz
FEEDING THE PROBLEM: Insulin and Fuel
Insulin levels have a direct impact on the fuel a horse's body uses during exercise, says Pagan. According to his studies at KER, here's how it works:
- You feed the horse a meal including grain, which causes an increase in blood glucose, leading to an increase in insulin levels.
- If you exercise the horse at this point, the insulin will convert the blood glucose directly into fuel, rather than burning fat.
- Unfortunately, blood glucose is the horse's smallest "gas tank," and when he runs out of this fuel, he becomes fatigued, and the nervous system is affected.
- If, instead, the horse begins exercise with resting (not elevated) levels of insulin, it will take fuel from the biggest tank--the most abundant fuel source--and that's fat. The body's fuels will then be used more efficiently and will be better able to support intense, prolonged exercise.
The studies have focused specifically on intense, prolonged forms of exercise, such as an endurance ride or the cross-country phase of a three-day event. "If you go to something like a Thoroughbred race, I don't know if this matters," says Pagan. "No one has tested it in short, high-intensity exercise."
In general, he adds, the impact of insulin levels on performance is important for high-level equine athletes. If you're riding for pleasure or at lower, less intense levels, he says, "Then you're feeding to reduce the risk of colic and maximize your convenience."--Sushil Dulai Wenholz
About the Author
Sushil Dulai Wenholz is a free-lance writer based in Lakewood, Colo. Her work appears in a number of leading equine publications, and she has earned awards from the American Horse Publications and the Western Fairs Association.
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