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Insulin May Prevent Thrombosis Leading To Heart Attack and Stro

Apr 22, 2002
 

Insulin may support the action of other clot busters and clot preventers currently used in heart attacks and strokes 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 University at Buffalo (UB) endocrinologists has shown.

The researchers have demonstrated that an infusion of insulin and glucose suppresses a factor that regulates genes for two proinflammatory proteins that promote coagulation and clot formation in smooth muscle tissue lining blood vessels.

Results of the study appear in 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, MD, UB 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 proinflammatory transcription factor, early growth response gene-1 (Egr-1), and concentrations in blood plasma of two proteins whose expression is regulated by Egr-1 – tissue 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% of preinfusion levels. PAI-1 levels had decreased on average to 58% and TF levels to 85% on average, compared with baseline.

Dandona said it is possible that insulin may support the action of other clot busters and clot preventers currently used in heart attacks and strokes.