Study in Rats Shows Hyperinsulinemia Drives Breast Cancer Risk

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A study using rats to test the effect of diabetes on breast cancer showed that hyperinsulinemia is an important factor that drives the risk of developing, and dying from, breast cancer in type 2 diabetes patients. The results of the study were presented by Derek LeRoith, MD, PhD, Chief of the Division of Endocrinology, Diabetes, and Bone Diseases at the Mount Sinai School of Medicine, during the session “The Links Between Diabetes and Cancer,” at the American Diabetes Association’s 70Scientific Sessions.

With the goal of seeing how obesity and diabetes can affect breast cancer development, LeRoith and colleagues injected mouse models so that they were born with severe hyperinsulinemia. At 6 weeks they were fully diabetic; at 8 weeks they had fasting hyperglycemia. Dr. LeRoith explained that the reason they converted from pre-diabetes to diabetes is because they hyper-secreted insulin; it’s this change in secretion that causes the conversion from pre-diabetes to diabetes.

The mice are born with severe insulin resistance in the muscle and an impaired glucose tolerance, but they weren’t obese, which differentiates them from humans with type 2 diabetes.

Dr. LeRoith said that his team believes that hyperinsulinemia is driving the insulin receptor (IR)-A, which causes breast cancer. They increased levels of insulin receptors, especially IR-A, and phosphorylation, which caused worse survival; the hyperinsulinemia made development of the tumor in mice more aggressive, leading them to conclude that hyperinsulinemia drives tumor growth. So insulin resistance, leading to hyperinsulinemia, interacting with the receptors, many of them IR-A, is what drives the growth of the tumor.

Knowing that they should be able to block the receptor to prove that it is the driving force behind tumor growth, Dr. LeRoith blocked the receptor. When the receptor was blocked the hyperinsulinemia gets much worse, but the extra growth of the tumor is blocked because of the receptor-block. Therefore, increased tumor growth is reduced by lowered hyperinsulinemia, which drove the tumor.

They also saw that the breast cancer MVT cells that were injected orthotopically metastasized to the lungs. This occurred in both the WT and MKR mice, but much more in the MKR mice.

From this study, as well as others others, Dr. Johnson concluded that it seems that endogenous hyperinsulinemia is one important factor driving the increased risk, and mortality from, breast cancer in type 2 diabetes.

“Endogenous hyperinsulinemia and insulin resistance is responsible for cancer risk and mortality, though obviously not alone,” said Dr. Johnson.