In First Human Trial, Insulin Shows Ability to Reduce Components that Inflame Vessel Walls

BUFFALO, N.Y. - Insulin, the hormone used to treat diabetes, also may have potential as a treatment for heart disease, a study conducted by endocrinologists at the University at Buffalo has shown.

The research shows for the first time that insulin produces an anti-inflammatory effect by decreasing concentrations of certain pro-inflammatory components in the bloodstream and increasing concentrations of components that help prevent inflammation and damage to cells lining blood vessels walls.

The study appeared in the July issue of The Journal of Clinical Endocrinology and Metabolism.

"This is a brand new property of insulin," said Paresh Dandona, M.D., UB associate professor of medicine and director of Kaleida Health's Diabetes-Endocrinology Center of Western New York.

"It is the first study of insulin's anti-inflammatory effect in humans and the results are clear. Since atherosclerosis is the result of an inflammation of the vessel wall, we believe insulin will prove to be anti-atherosclerotic in the long run.

"At the very least, these results should indicate to physicians that they should not be reluctant to prescribe insulin when it is indicated for fear that it may increase the risk of heart attack. It appears insulin has just the opposite effect. It may reduce the risk of heart attack."

Dandona and colleagues, in earlier laboratory-based research, had shown that insulin helps vessels to dilate by increasing the release of nitric oxide, a known vasodilator, and increasing expression of nitric oxide synthase, the enzyme that makes nitric oxide.

They also had shown that troglitazone, a substance that makes cells more sensitive to insulin, has anti-inflammatory effects, and that insulin decreased the expression of a component

called intracellular adhesion molecule-1 (ICAM-1), known to promote inflammation in the lining of the arteries that has been associated with an increased risk of coronary artery disease.

These results appeared to suggest that insulin may help protect against cardiovascular disease, rather than contributing to its development, as other researchers have assumed, Dandona noted.

Seeking to determine if insulin produced similar effects in humans, Dandona and colleagues infused insulin in a glucose solution into 10 obese nondiabetic volunteers (obese subjects show increased inflammation) and monitored levels of certain pro- and anti-inflammatory blood components. Blood samples were taken before the infusion began and at two, four and six hours into the procedure.

Researchers were particularly interested in concentrations of a component called nuclear factor (B (NF(B), which induces the production of pro-inflammatory cytokines, adhesion molecules and enzymes that generate cell-damaging free radicals. They also measured a component that inhibits NF(B, called I(B, and certain other anti-inflammatory components, as well as concentrations of adhesion molecules and free radicals.

Results showed that insulin infusion caused a fall in NF(B and an increase in its inhibitor. These changes began at two hours and peaked at four hours. NF(B returned to normal at six hours, but I(B continued to increase, even at six hours.

"These changes are consistent with an acute anti-inflammatory effect of insulin," Dandona said, "and suggest that in the long term, a persistent effect of this kind would indicate a potential antiatherogenic action of this hormone."

Also participating in the research were Ahmed Aljada, Ph.D., UB research assistant professor of medicine; Priya Mohanty, UB clinical instructor of medicine, and Husam Ghanim, Wael Hamouda, Ezzat Assian and Shakeel Ahmad, doctoral students working with Dandona.

The William G. McGowan Charitable Fund supported the work.