Rethinking insulin's effect
Study suggests insulin may help protect against heart disease

By LOIS BAKER
News Services Editor

Excess insulin in the bloodstream does not appear to contribute to atherosclerosis or arterial clogging, despite the known association of Type 2 diabetes with cardiovascular disease, a study by UB endocrinologists has shown.

The study, published in the July issue of The Journal of Clinical Endocrinology and Metabolism, showed that insulin reduced the expression of a molecule that promotes inflammation and clogging of arteries.

Paresh Dandona, professor of medicine, director of the Division of Endocrinology, Diabetes and Metabolism for UB and Kaleida Health, and senior author on the study, said the results indicate insulin may inhibit, rather than promote, clogged arteries.

"These are the first real findings showing that insulin may have an antiatherosclerotic role," Dandona said. "It turns the whole thinking about insulin upside down."

Type 2 diabetes, also known as adult-onset diabetes, has been linked to an increased risk of heart disease, but the precise nature of that link or links has eluded scientists. Persons with Type 2 diabetes usually produce sufficient insulin to metabolize sugar they consume, but their cells do not respond to insulin's action, creating a condition called insulin resistance. This results in increased sugar, in the form of glucose, in the bloodstream that, in turn, signals the body to produce even more insulin to lower glucose levels.

Researchers have speculated that this excess insulin, a condition called hyperinsulinemia, may contribute to vascular disease in diabetics, but no direct causal mechanism has been found. Dandona and colleagues earlier had shown insulin helps vessels to dilate by increasing release of nitric oxide, a known vasodilator, and increasing expression of nitric oxide synthase, the enzyme that makes nitrous oxide. These results suggested that insulin may help protect against cardiovascular disease, rather than contributing to its development.

To further assess insulin's potential as a protectant, Dandona and colleagues studied its role in the expression of a component called intracellular adhesion molecule-1 (ICAM-1). Increased concentrations in the bloodstream of ICAM-1, which is expressed by the endothelium, the cell layer lining blood vessels, and is known to promote inflammation in the lining of the arteries, has been associated with increased risk of coronary artery disease. The researchers set out to see if insulin may inhibit expression of ICAM-1.

Using human aorta endothelial cells, and exposing them to increasing amounts of insulin, the researchers were able to show that insulin decreased the expression of ICAM-1 and increased the expression of nitric oxide synthase and nitric oxide. To determine if the reaction was related directly to insulin's ability to increase nitric oxide, the researchers exposed the cells to a compound known to inhibit its production.

They found that when the production of nitric oxide was inhibited, the ability of insulin to stop ICAM-1 production also was impaired.

Also participating in the research were Ahmed Aljada, research assistant professor of medicine, and Rana Saadeh, Ezzat Assian and Husam Ghanim, doctoral students working with Dandona.

The William G. McGowan Charitable Fund, Inc. supported the work.