Unlikely Cause of Atherosclerosis

In humans, insulin resistance, a condition in which insulin becomes less effective at lowering blood sugar levels, coexists with hyperinsulinemia. Both are associated with atherosclerosis, the buildup of cholesterol in blood vessels that causes coronary artery disease, heart attack, and stroke.

In this condition, vascular cells could become dysfunctional because of hyperinsulinemia or because vascular cells themselves are insulin resistant, which is caused by increased insulin production from pancreatic beta cells as a compensatory mechanism to overcome insulin resistance.

Scientists have known for some time that insulin resistance and hyperinsulinemia cause increased lipids in the circulation, which indirectly leads to atherosclerosis. However, the Joslin study shows that, without other factors such as high blood pressure and high cholesterol, hyperinsulinemia alone does not cause atherosclerosis.

"For years, scientists have suspected that high levels of insulin could affect vascular cells negatively," says Doctor Christian Rask-Madsen of Joslin's Dianne Nunnally Hoppes Laboratory for Diabetes Complications. "We know that people with type 2 diabetes and insulin resistance are susceptible to atherosclerosis, but our study shows that excess insulin alone does not promote this complication."

To study the effects of hyperinsulinemia on atherosclerosis, Rask-Madsen and his colleagues created mice with fewer insulin receptors in every tissue of the body and compared them to mice with intact insulin receptors. Insulin receptors make cells responsive to insulin, a hormone that circulates in the bloodstream. Both sets of mice were genetically modified to have high cholesterol, but were similar in terms of body weight, glucose metabolism, and lipid and blood pressure levels.

Reducing the insulin receptors from one set of mice did not significantly impair their glucose metabolism, says Rask-Madsen — certainly not enough to make the animals overtly insulin resistant — but it did increase the amount of circulating insulin by reducing its removal from the blood. This model allowed the researchers to study the effects of hyperinsulinemia without the confounding effects of insulin resistance.

MEDICA.de; Source: Joslin Diabetes Centre