Type 1 diabetes is an autoimmune disease. The body does not recognize its own insulin-producing beta cells, so the immune system attacks and destroys them as if they were invaders. The body needs insulin to metabolize sugar and turn it into energy.
However, of these beta cells, some manage to survive. In fact, some of the cells persist and proliferate for years after the disease has started.
New research, led by professor of immunobiology Dr. Kevan Herold of Yale University in New Haven, CT, identifies the mechanism that explains how these beta cells survive the immune attack. The study was a collaboration with the Broad Institute of Massachusetts Institute of Technology and Harvard.
The findings were published in the journal Cell Metabolism.
Researchers find new subpopulation of beta cells
The scientists investigated the adaptive changes in beta cells that take place during the immune attack in both mouse models and in human cell culture. They used cyclophosphamide to accelerate the diabetes onset.
Herold and colleagues identified a resistant subpopulation of beta cells in 9-week-old, non-obese diabetic mice. The new subpopulation seems to develop from normal beta cells when they detect infiltration into the islet.
These new cells have a lower granularity, and they develop during the progression of type 1 diabetes.
"During the development of diabetes, there are changes in beta cells so you end up with two populations of beta cells. One population is killed by the immune response. The other population seems to acquire features that render it less susceptible to killing."
Dr. Kevan Herold
The new subpopulation is also less differentiated and displays stem-like properties. Much like stem cells, they have the ability to revert to a previous stage of development that enables them to survive and continue to replicate despite the immune attack.
As the study's senior author explains, these cells "duck and cover" as they develop molecules that inhibit the immune response. Human beta cells were revealed to go through similar changes when the researchers cultured them together with immune cells.
Although the cells do eventually die, the authors explain, the mechanism they uncovered might account for the long-term development of type 1 diabetes.
"Eventually, in [non-obese diabetic] mice as in humans, the majority of - if not all - [beta] cells are destroyed by immune effectors and products. However, the process is protracted. We have identified mechanisms that [beta] cells use to survive. Future studies that can recover mature [beta] cells from the pool of modified cells may identify ways of restoring normal metabolic function together with immune therapy," the authors conclude.
As Herold notes: "The next question is, can we recover these cells so that there is insulin production in someone [with] type 1 diabetes?"
Herold and team intend to conduct clinical trials to test drugs that might have the potential to change this subpopulation of beta cells, and transform it into insulin-producing cells.