News & Research

University of Louisville Research Foundation Inc. Louisville, Kentucky

Beta-catenin as a potential marker for T1D risk and new therapeutic target.

General Research Subject: Type 1 Diabetes

Focus: Immunology, Signal Transduction (Non-Insulin Action)\Cytokines and Apoptosis

Type of Grant: Basic Science

Project Start Date: January 1, 2010

Project End Date: December 31, 2012

Research Description

A major problem in modern industrialized countries is the growing incidence of autoimmune diseases, including Type I diabetes, and the associated absence of effective therapy. Our goal is to find alternative treatments that prevent and ameliorate disease in susceptible individuals. An ideal animal model to study diabetes is the non obese diabetes (NOD) mouse, which spontaneously develops disease resembling human diabetes. In NOD mice, a population of cells, termed APC, produce elevated levels of pro-inflammatory cytokines, which have been implicated in diabetes development. We have found that NOD APC express abnormally high levels of a molecule, ß-catenin. Our data also indicate that ß-catenin may be responsible for the high levels of pro-inflammatory cytokines produced by NOD APC. We hypothesize that excess ß-catenin accumulation in APC may drive pro-inflammatory cytokine production and the subsequent development of diabetes in individuals predisposed to develop T1D.

In the present study, we will determine the contribution of ß-catenin to the development of diabetes. We will also attempt to identify the mechanisms that may lead to the increase in nuclear ß-catenin and the resulting enhanced pro-inflammatory cytokine production by NOD APC. Determining the cause of the defect in ß-catenin expression as well as how it influences the production of pro-inflammatory cytokines and therefore diabetes development may lead to new therapy to prevent and/or cure type 1 diabetes. Ultimately, the results of this study should provide the basis for the development of promising treatments for human diabetes.

Researcher Profile

What area of diabetes research does your project cover? What role will this particular project play in preventing, treating and/or curing diabetes? 

My project covers type 1 diabetes, and more specifically the events leading to diabetes development. This project directly deals with diabetes prevention in two aspects. The first aspect is the role that the molecule we are studying may play as a biomarker to diagnose individuals that may develop type 1 diabetes. The second aspect is the use of drugs directed at this molecule to attempt to prevent diabetes development, via abrogation of the induction of immune cells that destroy the insulin-producing pancreatic cells.

If a person with diabetes were to ask you how your project will help them in the future, how would you respond? 

A person with type 1 diabetes exhibit a loss of cells capable of producing insulin as a consequence of the cells of the immune system attack. The possibility of regenerating these cells has emerged with stem cells research. However, in a case of successful regeneration of insulin-producing cells, these new cells will again be lost because the activated cells of the immune system will still recognize them and attack them. Our project is attempting to abrogate the induction of cells that have the ability to destroy any insulin-producing cells.

Why is it important for you, personally, to become involved in diabetes research? What role will this award play in your research efforts? 

It is important for me to dedicate my efforts to prevent and or cure a disease, in this case diabetes, rather than working on a more basic project with no direct application to disease.

This award will allow us to pursue our research which we feel could have two potential impacts on preventing and/or treating type 1 diabetes. The first impact is based on the fact that the molecule which we have found abnormally expressed in cells from type 1 diabetic mice and diabetic patients could be a potential marker for type 1 diabetes. Expression of this molecule could therefore allow to screen high-risk patients before any signs of disease. The second impact is based on the fact that elevated levels of this molecule appears to be associated with a profile of inflammatory mediators that may induce the cells that destroy the insulin-producing pancreatic cells. Drugs directed at this molecule may allow us to prevent the induction of these destructing cells, and prevent and/or ameliorate disease outcome.

In what direction do you see the future of diabetes research going? 

Prevention of diabetes is an important direction to take. With the progress that are being made in stem cell research, it would be possible in the near future to restore functional insulin-producing beta cells in patients with type 1 diabetes. However, restoring insulin production is insufficient, since immune cells capable of eliminating these new pancreatic cells will still be induced. It is, therefore, very important to find potential treatments that may inhibit disease development. It is as important to find biomarkers that could allow doctors to determine whether a particular individual exhibits a high probability to develop disease, in order to be able to prevent disease development with potential promising treatments.