Type 1 diabetes (or T1D) is caused by a selective destruction of the body’s insulin-producing cells resulting from chronic inflammation of the pancreatic islet cells. The goal of this project is to discover, prior to patients exhibiting symptoms, the initial changes that take place in human islets, which are believed to cause insulin-producing cell loss at the onset of diabetes. These findings will then lead to an understanding of how this destructive process can be Blocked.
This project focuses on a specific tissue component named hyaluronan (or HA). Inflamed tissues have an abundance of HA which can influence the behavior of other cells. The intention is to determine how and why large amounts of HA are formed in human islets in the early stages of T1D. Early stages are characterized by the presence in blood of islet cell autoantibodies (or aAbs), a condition known as islet autoimmunity. Islet aAbs are used as markers to predict T1D. When T1D first starts, one type of islet cell aAb is measured in blood, but several years later, two or more types are detected. This project proposes that a modified HA-rich cell forms in human islets during the early stage of T1D when only one or two aAbs are detected. We believe that under the effect of inflammatory stimuli, islet cells make more HA, which then triggers insulitis and alters islet integrity and structure causing damage to the insulin-producing cells.
