Insulin
found to help stop clots
By LOIS BAKER
Contributing Editor
Insulin
may interfere with the cascade of reactions that promote clot formation
and platelet aggregation in heart-attack patients and may help prevent
clot formation and plaque development in persons at risk of heart attack
and stroke, new research by UB endocrinologists has shown.
The
researchers have demonstrated that an infusion of insulin and glucose
suppresses a factor that regulates genes for two pro-inflammatory proteins
that promote coagulation and clot formation in smooth muscle tissue
lining blood vessels.
Results
of the study appear in the March issue of the Journal of Clinical
Endocrinology and Metabolism.
"Our
earlier research showed for the first time that insulin exerts a significant
anti-inflammatory effect on blood vessel walls, and now we have linked
insulin with the mechanisms that reduce clotting factors," said Paresh
Dandona, professor of medicine and senior author on the study.
"These
new findings suggest that insulin has the potential to prevent thrombosis
that leads to heart attack and stroke. It also may be useful to treat
persons with those conditions through the prevention of clotting and
promotion of dissolution of clots."
Dandona
said the findings in this study add relevance to results from the Diabetes
and Insulin-Glucose Infusion in Acute Myocardial Infarction (DIGAMI)
study, conducted in Stockholm, which showed that diabetic patients experiencing
an acute heart attack who received a low-dose infusion of insulin and
glucose had a better outcome than patients who weren't infused.
"The
DIGAMI study showed that insulin has a positive effect on acute myocardial
infarction, but the mechanisms weren't clear," he said. "Our studies
are defining the mechanisms."
The
current investigation targeted a pro-inflammatory transcription factor,
early growth response gene-1 (Egr-1), and concentrations in blood plasma
of two proteins whose expression is regulated by Egr-1tissue factor
(TF) and plasminogen activator inhibitor-1 (PAI-1).
The
gene responds rapidly to a variety of stimuli related to tissue oxygen
deprivation and physical damage to blood vessels, Dandona said, and
appears to play an important role in the development of human and mouse
atherosclerosis. The protein TF leads, via a complex cascade of actions,
to the formation of fibrin, the essential ingredient of a blood clot,
while fibrin's predecessor, thrombin, is a powerful aggregator of platelets,
a primary component of arterial plaque. The protein PAI-1 prevents the
normal breakdown of fibrin, which would help prevent clotting.
In
this study, 10 subjects who had high levels of the factors in question
due to obesity received an intravenous solution of insulin, plus dextrose.
The dextrose prevents hypoglycemia, or low blood sugar. They provided
fasting blood samples before infusion and at two, four and six hours
following infusion.
The
samples were assayed for Egr-1, and both proteins. Results showed that
after four hours of infusion, blood levels of Egr-1 had fallen, on average,
to 47 percent of pre-infusion levels. PAI-1 levels had decreased on
average to 58 percent and TF levels to 85 percent on average, compared
to baseline.
Dandona
said it is possible that insulin may support the action of other clot
busters and clot preventers currently used in treating heart attacks
and strokes.
Additional
researchers on the study were Ahmad Aljada, research assistant professor
of medicine; Husam Ghanim, doctoral student working with Dandona; Priya
Mohanty, clinical instructor of medicine, and Neeti Kapur, research
assistant.
The
research, supported by the McGowan Charitable Fund, was conducted at
the Diabetes-Endocrinology Center of Western New York, which Dandona
directs.