By LOIS BAKER
Contributing Editor
Insulin, the hormone used to treat diabetes, also may have potential
as a treatment for heart disease, a study conducted by UB endocrinologists
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, 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 kB (NFkB), 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 NFkB, called
IkB, 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 NFkB and an
increase in its inhibitor. These changes began at two hours and peaked
at four hours. NFkB returned to normal at six hours, but IkB 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, research assistant
professor of medicine; Priya Mohanty, 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.