-Study provides important clue in type 1 diabetes; could help scientists identify and validate
potential drug targets to alleviate ER stress and preserve beta cell mass in T1D -
NEW YORK, March 22, 2011 --- In type 1 diabetes (T1D), pancreatic beta cells die from a misguided
autoimmune attack, but how and why that happens is still unclear. Now, JDRF-funded scientists from
the Indiana University School of Medicine have found that a specific type of cellular stress takes place in pancreatic beta cells before the onset of T1D, and that this stress response in the beta cell may in fact help ignite the autoimmune attack. These findings shed an entirely new light into the mystery behind how changes in the beta cell may play a role in the earliest stages of T1D, and adds a new perspective to our understanding how T1D progresses, and how to prevent and treat the disease.
In the study, published in the March 22 issue of the journal Diabetes, the researchers, led by Sarah
Tersey, Ph.D., assistant research professor of pediatrics, and Raghavendra Mirmira, M.D., Ph.D.,
professor of pediatrics and medicine at the Indiana University School of Medicine, show for the first
time in a mouse model of T1D that beta cells become stressed early in the disease process, before the animal develops diabetes. In response to the stress, beta cells activate a cell death pathway leading to the loss of beta cell mass in the animal.
In all cells, there is a vital compartment known as the endoplasmic reticulum (ER) where secreted
proteins, like insulin, are produced and processed before being released by the cell. Pancreatic beta cells are highly specialized for the production and secretion of insulin and therefore, the ER plays a critical role in their function, making them particularly sensitive to ER stress. The study by Tersey and colleagues show that an alteration of the beta cell ER stress response occurs early in the disease, and if the ER stress is not resolved properly, it can result in defects in insulin secretion, and ultimately death of the beta cell.