Cytokines, Inflammation, and Insulin Resistance: Dangerous Liaisons

Systemically or critically ill horses, such as those with sepsis (a whole-body inflammatory state caused by infection), might have a better chance of survival if their insulin is controlled, researchers from the University of Kentucky's Gluck Equine Research Center reported earlier this month.

Insulin resistance, the body's inability to control blood sugar levels with normal amounts of insulin, is known to be associated with equine obesity, altered reproductive function, and pasture-associated laminitis. In addition, insulin resistance also develops in horses during periods of systemic inflammation.

According to Mandi Vick, PhD, and Barry Fitzgerald, PhD, co-authors on this study, a relationship between obesity, insulin resistance, and increased levels of circulating inflammatory mediators and molecules, known as cytokines, has previously been identified.

"We hypothesize that inflammation directly results in insulin resistance and that adipose tissue, the fat reserves in the body, participates in the development of inflammation and insulin resistance," explained Fitzgerald. Together, these series of events could predispose horses to develop complications, including laminitis.

The purpose of this study was to determine if insulin resistance could be induced in horses after creating a systemic inflammatory state by intravenously injecting the pro-inflammatory substance lipopolysaccharide (LPS, a major constituent of Gram-negative bacteria cell walls).

Results revealed that LPS caused an overall decrease in insulin sensitivity by 24 hours post-injection. Further, the production of cytokines was increased in both blood and adipose tissue.

"These data suggest that systemic inflammation contributes to the development of insulin resistance and that adipose tissue, which was previously thought to be simply a way for the body to store fat, is, in fact, a dynamic tissue capable of contributing to the body's inflammatory response," summarized Fitzgerald.

In addition, the results indicate that obese animals with an excess of adipose tissue might have an increased inflammatory response compared to lean animals, ultimately causing them to experience enhanced tissue damage or be at a higher risk for complications such as laminitis.

Future research efforts will be aimed at controlling the development of insulin resistance in sick horses to see if this helps minimize laminitis and other life-threatening complications.

The study, "Effects of systemic inflammation on insulin sensitivity in horses and inflammatory cytokine expression in adipose tissue," was published in the January edition of the American Journal of Veterinary Research.

About the Author

Stacey Oke, DVM, MSc

Stacey Oke, MSc, DVM, is a practicing veterinarian and freelance medical writer and editor. She is interested in both large and small animals, as well as complementary and alternative medicine. Since 2005, she's worked as a research consultant for nutritional supplement companies, assisted physicians and veterinarians in publishing research articles and textbooks, and written for a number of educational magazines and websites.

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