Research led by Harvard School of Public Health demonstrates a disease mechanism in type 1 diabetes (T1D) that can be targeted using simple, naturally occurring molecules to help prevent the disease. The work highlights a previously unrecognized molecular pathway that contributes to the malfunction of insulin-producing pancreatic beta cells in T1D in human patients and in mice, and shows that a chemical intervention can help beta cells function properly and survive. The study appears online in Science Translational Medicine.
In T1D, beta cells are attacked by the body's immune system. Prior research has focused on ways to prevent this autoimmune response. This study shows that beta cell preservation is possible even in the face of such an immune attack. Using human pancreatic samples and mouse models, researchers sought to tease apart the mechanisms of beta cell failure in T1D. They honed in on the function of the endoplasmic reticulum (ER)—a “mini-organ” inside cells where proteins and lipids are processed and packaged before they reach their destinations in the body. The ER is known to play a key role in supporting the work of beta cells.
The researchers found that, in animal models and in humans with T1D, ER function is compromised by the immune attack. This reduced ER function results in ER stress and contributes to the death of beta cells and insulin insufficiency. Earlier studies showed that ER stress can be corrected with “chemical chaperones” such as tauroursodeoxycholic acid (TUDCA), a bile acid. Based on that previous research, the scientists applied TUDCA to mouse models of T1D. ER function improved—both in mice with diabetes and with pre-diabetes. Read the study abstract.