Researchers Identify Key Protein Fragment that May Trigger Type 1 Diabetes

While the basics of type 1 diabetes (T1D) have been understood for years—the body’s immune system mistakenly destroys insulin-producing beta cells—the reasoning behind it has remained a mystery. Researchers have yet to identify exactly why this process occurs and what causes it. They may be a step closer as a recent study shows that an altered protein fragment may be the culprit.

The human body is filled with T cells that are constantly on the lookout for foreign bodies and infected cells. When their receptors sense these problems, they activate the immune system to destroy the affected cells. Normally, any T cells with receptors for proteins that occur naturally within the body are destroyed before they make it out of the thymus. This prevents them from attacking proteins that should be in the body, which in this case are insulin proteins. But scientists believe that some may escape before this process occurs, and therefore they mistakenly trigger an attack against insulin-producing cells which in turn leads to type 1 diabetes.

Researchers took a closer look at the structures that bind T cells to insulin fragments and found a specific fragment that may activate T cells to destroy insulin-producing cells. It is known as the B:14-22 fragment. They created a molecule where all of the pathogenic T cells and protein fragments fit very tightly together, but in order to improve their connection, they altered the insulin fragments. In doing so, they found that this activated the pathogenic T cells which led to an autoimmune attack on the cells.

They found that the body naturally creates altered fragments through a process called transpeptidation. When proteins are broken apart in the cell, they are recycled and may fuse together with other protein fragments. This generates a new configuration of proteins. Researchers believe that some of these new fragments could have just the right structure to activate T cells leading to the development of type 1 diabetes.

These findings may help scientists to create more effective methods for preventing and treating type 1 diabetes. Having a better understanding of what is happening on a cellular and molecular level allows for more targeted focus on coming up with a cure.

The Diabetes Research Connection (DRC) is excited to see where this study may lead and what it could mean for future diabetes treatment. It may also stimulate new studies from other researchers building on these findings. The DRC provides critical funding to early career scientists in order to support novel research on type 1 diabetes. Empowering more research could open new doors.


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