UB Study Suggests Insulin May Help Protect Against Coronary Artery
Disease
Release date: Thursday, August 10, 2000
Contact: Lois Baker, ljbaker@...
Phone: 716-645-5000 ext 1417
Fax: 716-645-3765


http://www.buffalo.edu/news/fast-execute.cgi/article-page.html?
article=48350009

BUFFALO, N.Y. -- 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 University at Buffalo 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, M.D., UB 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 the sugar they
consume, but their cells do not respond to insulin's action, creating
a condition called insulin resistance. This results in an increase in
sugar -- in the form of glucose -- in the bloodstream which, in turn,
signals the body to produce even more insulin to lower the 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 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
nitrous oxide. These results appeared to suggest 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 this molecule, which is expressed by the
endothelium -- the layer of cells lining blood vessels -- and is
known to promote inflammation in the lining of the arteries, has been
associated with an increased risk of coronary artery disease. The
researchers set out to determine whether insulin may inhibit the
expression of ICAM-1

Using human aorta endothelial cells that had been incubated for two
days, 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.

"This finding directly linked insulin's ability to stop production of
molecules that increase the risk of cardiovascular disease to its
ability to increase production of the vasodilator nitric oxide in the
blood vessel lining," Dandona said. "The data suggest that insulin
may potentially protect people at risk of CVD, and we are currently
investigating this effect of insulin in humans."

Also participating in the research were Ahmed Aljada, Ph.D., UB
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.