A discovery in mice suggests a new opportunity for reducing the incidence of type 1 diabetes.
Type 1 diabetes is on the rise. Scientists are not exactly sure why this is, but the increase in new cases makes the race to understand this life-threatening condition more urgent than ever.
A new study appearing in the journal Science Immunologysuggests that a switch causes the body’s immune system to start destroying its insulin, resulting in the onset of diabetes.
If this discovery in mice translates to humans, it could enable early detection and the development of preventive therapies for type 1 diabetes.
Human cells derive energy from glucose, which is a sugar in the bloodstream. Insulin, a hormone produced by beta cells in the pancreas’ islets of Langerhans, allows the body to absorb glucose.
In a healthy individual, the beta cells produce enough insulin to allow the body to consume the available glucose in the bloodstream. However, a lack of sufficient insulin can be fatal.
In type 1 diabetes, the body’s immune system attacks and destroys the beta cells that produce insulin. This deprives the body’s cells of the energy that glucose would otherwise provide.
In the United States, about 1.25 million people living with type 1 diabetes depend on continual monitoring of blood sugar and injections of insulin. Some people with type 2 diabetes also require insulin therapy, as their beta cells have stopped producing insulin.
A landmark study carried out over 40 years ago revealed a link between type 1 diabetes and a certain versions of HLA (human leukocyte antigen). These proteins live on the surface of cells and instruct the immune system to attack foreign organisms and substances.
The specific forms of HLA that carry a greater association with type 1 diabetes cause a change in how insulin fragments are presented to T cells.
How this process works and why this primes T cells to destroy beta cells remains an unanswered question.
The new report, authored by scientists from Scripps Research, and led by professor of immunology and microbiology Luc Teyton, M.D., Ph.D., has uncovered a likely mechanism, at least in mice.
Through a series of experiments over 5 years, Prof. Teyton’s team examined blood samples from nondiabetic, overweight mice deemed to be candidates for the disease.
The scientists sequenced individual T cells from the subjects’ blood and then analyzed the 4 terabytes of data their sequencing had produced.
“By using single-cell technologies to study the prediabetic phase of [the] disease, we have been able to mechanistically link specific anti-insulin T cells with the autoimmune response seen in type 1 diabetes,” says Prof. Teyton.
The scientists’ analysis revealed a mechanism they dubbed the “P9 switch.” This allowed a particular population of T cells, which can preferentially bind to the HLA types associated with type 1 diabetes, to attack beta cells.
However, cells using this mechanism existed for just a short while, causing a flurry of insulin destruction and then disappearing altogether. This could explain why other researchers have not seen similar results in people with diabetes — the switch cells are long gone by the time diabetes symptoms appear.
If these insights apply to humans, they could constitute a first step toward the prevention of type 1 diabetes. “The translational aspect of this study is what’s most exciting to me,” admits Prof. Teyton.
He has received approval to begin investigating whether his findings could apply to humans.
Type 1 diabetes has a strong genetic association — for those who have an immediate relative with the disease, the risk of developing it is 20 times greater.
Prof. Teyton and his team plan to search for the telltale P9 switch cells in the blood of 30 such at-risk subjects who have not yet experienced symptoms of the disease.
If the researchers do find the switch and confirm its role in human type 1 diabetes, the discovery could offer doctors and people a new opportunity for early detection. It could also provide a time window during which scientists can develop new therapies to prevent the development of this life-threatening condition.