Prediabetes/Insulin Resistance Research

Through its Research Program, the ADA is determined to help people with prediabetes and insulin resistance prevent the development of type 2 diabetes. Projects include understanding the role of exercise, novel therapies, and more.

Scott Summers, PhD

University of Utah

Genes, Environment, and Diabetes: Convergence on Ceramides

“My interest in diabetes results developed when my I was 14 and my father came down with the disease. At that time, I apparently told him I would try to find a cure, and I've been working hard to do so ever since. Our work seeks to identify genetic causes of diabetes, which we will be able to use to develop new therapies.”

The problem: Both genetic and environmental factors contribute to diabetes, but the mechanisms by which the interact with each other to influence risk are unclear. A better understanding of how genetic factors synergize with environmental factors to influence risk would greatly advance our ability to prevent and personalize treatment for diabetes.

The project: The researchers have identified humans with genetic variants which leave them susceptible to insulin resistance. Insulin resistance prevents insulin from promoting glucose uptake into cells. Now, Dr. Summers and his team want to determine how changes in diet prevent or exacerbate development of insulin resistance.

The potential outcome: The work conducted in this project could uncover new ways to identify at-risk patients and inform about therapeutic approaches for combating diseases associated with obesity.

Janice M. Huss, PhD

Beckman Research Institute of City of Hope

Project: Estrogen-related Receptor alpha mediates skeletal muscle genetic and metabolic response to exercise

“As a basic scientist I can inform and encourage friends and family members with pre-diabetes about diet and exercise to improve their glucose control and potentially reduce the necessity for insulin sensitizing drugs. However, I feel more empowered when I tell them that our research will have a direct impact on the development of new treatments for diabetes and pre-diabetes.”

The problem: Exercise is a potent lifestyle intervention to prevent and treat obesity and insulin resistance, mainly through its effects on skeletal muscle metabolism. However, because of the increasing demands of everyday life in the 21st century, the challenge of compliance with regards to exercise limit its effectiveness in practice.

The project: Targeting molecular pathways that are involved in the benefits of exercise offers a way to mimic exercise without the need for physical exertion and is an attractive alternative to prevent obesity-related diabetes. This proposal will investigate one such molecular pathway – the ERRalpha pathway – proposed to be involved in the benefits of exercise to determine if it may

The potential outcome: The proposed studies will establish the ERRalpha pathway as a central player responsible for the beneficial effects of exercise and aid the development of therapeutics that mimic the beneficial effects of aerobic exercise.

Jingshi Shen, PhD

University of Colorado at Boulder

Project: Dissect insulin‐stimulated GLUT4 exocytosis using CRISPR genetic screens

“I find it highly motivating to directly link our research to diabetes patients who urgently need effective treatments. This ADA Innovative Basic Science Award will enable us to perform genetic screens of insulin responses at an unprecedented scale, a high-risk, high-reward project that could not be funded by conventional federal funding mechanisms.”

The problem: Insulin resistance is the process by which a person’s body – mainly muscle, liver and fat – become unresponsive to the hormone insulin, causing blood sugar to rise. Even though we have learned a lot about how and why this occurs over the past few decades, medications to improve insulin resistance have been slow to develop.

The project: Innovations in biotechnology have revolutionized tools available to researchers, which were not possible even a few years ago. Now, Dr. Shen will use one of these new tools – called CRISPR – which enables scientists to make extremely accurate edits to DNA. His goal is to use CRISPR to determine the precise molecular pathways by which insulin works to promote glucose lowering, and what goes awry when cells become resistant to insulin.

The potential outcome: Successful completion of this project will provide key insights into insulin action and blood glucose homeostasis. Ultimately, these findings will pave the path for developing new therapeutic strategies for insulin resistance and type 2 diabetes.