In the current research, investigators 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 vascular endothelium.

"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, M.D., senior author of 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 these findings add relevance to results from the Diabetes and Insulin-Glucose Infusion in Acute Myocardial Infarction (DIGAMI) study, conducted in Stockholm, Sweden, which showed that diabetic patients experiencing an acute myocardial infarction who received a low-dose infusion of insulin and glucose had a better outcome than patients who were not 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) and concentrations in blood plasma of two proteins whose expression is regulated by that gene (tissue factor and plasminogen activator inhibitor-1).

Dandona said that gene expression responds rapidly to a variety of stimuli related to tissue ischemia and physical damage to blood vessels, and gene activity appears to play an important role in the development of human and mouse atherosclerosis. The protein called tissue factor leads via a cascade of actions to formation of fibrin. The protein plasminogen activator inhibitor-1 prevents the normal breakdown of fibrin.

In the current research, 10 subjects with high levels of the factors in question due to obesity received an intravenous solution of insulin and dextrose. They provided fasting blood samples before infusion as well as samples at two, four and six hours following infusion.

The samples were assayed for the gene product and both pro-inflammatory proteins. Results showed that after four hours of infusion, blood levels of early growth response gene-1 had fallen on average to 47 percent of pre-infusion levels. Plasminogen activator inhibitor-1 levels had decreased on average to 58 percent and tissue factor levels to 85 percent on average, both compared with baseline.