Study provides first physiological evidence that insulin is critical for blood vessel formation

For people with type 2 diabetes, the death rate from a first heart attack is two to three times the death rate of patients without the disease. Similarly, patients with diabetes and ischemic (reduced blood flow) heart disease have a much higher mortality rate than the general population.

Now, a team of researchers at Joslin Diabetes Center led by George L. King, M.D., director of research and head of vascular cell biology, and Zhiheng He, M.D., Ph.D., a Juvenile Diabetes Research Foundation International Research Fellow and former Iacocca Fellow, has shown a potential physiological mechanism behind this difference. The discovery could one day lead to new treatments to improve the ability of patients with diabetes to survive heart attacks and live with coronary artery disease. The report was published in the Feb. 9, 2006, online edition of the American Heart Association journal, Arteriosclerosis, Thrombosis, and Vascular Biology.

Normally, when a coronary artery becomes blocked, the body responds by forming new blood vessels around the blockage to maintain blood and oxygen flow and limit heart damage. Heart cells produce the vessels by making VEGF, a growth factor that causes new blood vessel formation. “We have long recognized that in patients with diabetes, this blood vessel formation is not as robust as in people without diabetes,” says King, professor of medicine at Harvard Medical School. “Now we have a potential explanation.”

The researchers showed that insulin is the source of the signal the heart cells need to increase VEGF production. “We found that when insulin in the bloodstream binds with the insulin receptors on the outer membranes of heart cells, it activates the PI3K/AKT pathway, which is the pathway that produces VEGF,” says King. “We also found that this response is blunted in patients with insulin resistance, a major cause of type 2 diabetes that makes it harder for cells to use insulin. The heart produces less VEGF and forms fewer new blood vessels.”