Endocrinologists solve piece of insulin puzzle
Work finds that insulin increases enzyme that causes blood vessels to dilate

By LOIS BAKER
News Services Editor

Insulin, the hormone produced by the pancreas that enables cells to absorb sugars, also is known to dilate blood vessels. This action is a boon to the heart because it allows blood to flow more easily and under less pressure.

Precisely how this action occurs is a puzzle. But researchers have shown that when insulin comes into contact with cells in the blood-vessel lining, it induces the release of nitric oxide, a known blood-vessel dilator.

Endocrinologists from UB now have supplied a piece to this puzzle by showing for the first time that insulin causes cells in the blood-vessel lining to increase secretion of nitric oxide synthase, the enzyme responsible for nitric oxide production. That is, insulin increases the enzyme, which creates more nitric oxide, which results in dilation.

Results of the research, headed by Paresh Dandona, professor of medicine and director of the Diabetes-Endocrinology Center of Western New York, appear in the February issue of Metabolism.

"This new observation is important because it provides the molecular basis for the known vasodilatory effects of insulin," Dandona noted. Ahmad Alijada, a graduate student in the Department of Biochemistry and the Division of Endocrinology in the School of Medicine and Biomedical Sciences, conducted the research in Dandona's laboratory.

The study used cells from the linings of the aorta, lower-limb veins and umbilical cord, and from microscopic vessels permeating fat tissue. An initial exposure of each cell group to insulin in vitro showed the aortic cells to be the most responsive to insulin, so Dandona's group concentrated their research on these cells.

They introduced insulin into the cell cultures in increasing concentrations from 25 to 1,000 microunits-per-milliliter for a total of six days. These amounts of insulin are similar to what would occur normally and in patients with obesity and type 2 (adult-onset) diabetes, Dandona said.

Results showed that nitric oxide synthase increased as the amount of insulin increased, with the highest concentration of insulin resulting in a 250 percent rise in the amount of enzyme above baseline.

In addition to providing new information on the mechanism underlying insulin's vasodilatory effect, these findings lend insight into the relationship between hardening of the arteries and insulin resistance/diabetes, conditions that often exist in tandem.

"The lack of insulin or resistance to the action of insulin will cause the vessel constriction and increased aggregation of platelets known to occur in diabetes mellitus, Dandona stated. "Furthermore, the fact that nitric oxide also may reduce the expression of adhesion molecules on the surface of cells lining blood vessels may prevent cells from adhering to the vessel lining. This adhesion is one of the initial events in arterial hardening and blockage.

"Cell adhesion leads to cell activation, generation of free radicals, foam-cell formation and accumulation of foam cells inside vessels, which eventually form a fatty streak," Dandona noted. "This is the first visible sign of atherosclerosis. So we can say that insulin's stimulatory effect on nitric oxide synthase may help protect against hardening of the arteries.

"Knowing the molecular mechanism responsible for this action brings us closer to understanding the relationship between heart disease and diabetes, and may enable physicians to make more extensive use of insulin's vasodilatory effect," Dandona said.