News & Research

Beta cells are the insulin secreting cells located in the pancreas. Their impairment is significant to both type 1 and type 2 diabetes. In type 1 diabetes, the beta cells have been destroyed and therefore cannot produce insulin. In type 2 diabetes, the beta cells either do not produce enough insulin or the body ignores the insulin that is produced. Beta cell research is one area that the American Diabetes Association funds to better understand what causes beta cell dysfunction.

Meet Louis Philipson, MD, PhD an ADA- Research Award recipient conducting research at the University of Chicago. His research project is entitled, "Beta cell damage due to reactive species-induced oxidative stress." Using both rodent and human islets, he is conducting his research utilizing optical imaging technologies and three – dimensional electron microscopy to visualize reactive oxygen species production inside beta cells. Dr. Philipson says of his ADA award, "This award will allow us to continue our studies in an area of research that we have not had specific funding for previously. We can generate additional new data and use this to develop a translational research effort for this project."

Reactive oxygen species (ROS) are small molecules that are highly reactive with other molecules and are produced during normal processes where oxygen is metabolized. One category of ROS, free radicals, is created in the beta cell mitochondria. During times of oxidative stress, when there is an excess amount of reactive oxygen, free radicals circulate and can cause damage to critical beta cell components. Beta cells could be subject to injury from excess free radicals, become damaged and may potentially lead to reduced insulin secretion.

Previous studies conducted by Dr. Philipson have focused on the production of free radicals by the beta cell mitochondria. Continuing his efforts, he will delve further into the relationship between the production of insulin and the generation of free radicals. During insulin production, the molecules change shape (insulin folding) and form bonds causing the generation of more free radicals – three for each bond. These disulfide bonds are critical to the proper shape change of the insulin molecule but may also be the cause of potential beta cell injury. In parallel results, Dr. Philipson’s investigative data also demonstrated that another molecule, nitric oxide, is created in the beta cells and could act to protect the beta cells by dissipating the damaging free radicals thus prolonging their life.

In a second set of experiments and results, Dr. Philipson investigated mutations of the human insulin gene using the Akita Mouse model. During his years of ADA-funded research, Dr. Philipson has increased our knowledge of the number of known human insulin gene mutations from ten to twenty-five. The mutations were predicted to interfere with the normal processes of insulin folding by interrupting proper disulfide bond formation. Insulin mutation can cause permanent neonatal diabetes, a form of diabetes that develops during the first six months of life. Permanent neonatal diabetes differs from type 1 in that it is not due to an autoimmune response.

During the last year of his ADA-funded project, Dr. Philipson will continue to study the Akita mouse model for stress indicators due to insulin mutation and look for treatment therapies that will translate into human use, potentially leading to viable treatments to improve the disease. Previous studies using antioxidants have not shown to be very effective for treating diabetes, so he will focus on drugs with dual mechanisms of action that include increasing the native cellular defenses of the beta cell against free radicals. Dr. Philipson says, "Since it has become clear that loss of beta cell function is a critical aspect of type 2 diabetes as well as type 1, treatments that help preserve or enhance beta cell function would have an important role in preventing and treating diabetes."

Currently, Dr. Philipson is the Director of the Comprehensive Diabetes Center at the University of Chicago. He is also a member of the local and National Boards of the ADA.