New Study Flips the Script on Cause of Type 1 Diabetes
February 27, 2017 | by Katie Neith
For decades, scientists believed that the root cause of type 1 diabetes (T1D) was the immune system mistakenly identifying insulin-secreting beta cells as a potential danger and, in turn, destroying them.
This is because T1D — a disease that affects an estimated 1.5 million Americans and was previously known as juvenile diabetes — is the result of the unexplained loss of cells in the pancreas that produce insulin.
Now, a study led by City of Hope’s Bart Roep, Ph.D., the Chan Soon-Shiong Shapiro Distinguished Chair in Diabetes and professor and founding chair of the Department of Diabetes Immunology, turns that idea on its head.
“Our findings show that type 1 diabetes results from a mistake of the beta cell, not a mistake of the immune system,” said Roep, who is director of the The Wanek Family Project for Type 1 Diabetes, which was recently created with gifts from the Wanek family and anonymous donors to support the institution’s goal of curing T1D in six years. “The immune system does what it is supposed to do, which is respond to distressed or 'unhappy' tissue, as it would in infection or cancer.”
Roep, along with researchers from the Leiden University Medical Center in the Netherlands, published study results showing this outcome in the Feb. 27 issue of the journal, Nature Medicine.
In the paper, the team outlined a mechanism by which stressed beta cells are actually causing the immune response that leads to their own demise. When beta cells are destroyed, the body no longer makes insulin and therefore cannot distribute glucose — a simple sugar we get from eating that is used by the body for energy — causing T1D and, ultimately, the need to artificially supplement insulin.
To gain a better understanding of why the immune system attacks the body’s own source of insulin — the pancreatic beta cells — the team took some clues from cancer molecules that are also targeted by the immune system after successful treatment of the cancer with immunotherapy.
One of these cancer targets is a so-called “nonsense” protein, a nonfunctional protein that is the result of a misread DNA sequence. It turns out that the same type of protein error is also produced by the beta cells in T1D.
Roep and the other researchers believe it is a “wrong read” of the insulin gene itself that causes problems. This faulty product of the insulin gene is created when beta cells are stressed, said Roep.
“Our study links anti-tumor immunity to islet autoimmunity, and may explain why some cancer patients develop type 1 diabetes after successful immunotherapy,” he said. “This is an incredible step forward in our commitment to cure this disease.”
The results of the study give Roep new insight, he said, for his work — and for other scientists in the Diabetes & Metabolism Research Institute at City of Hope — in developing new vaccines to desensitize the immune system so that it will tolerate islets again, as well as for research into combining immunotherapy with more traditional diabetes treatments to reinvigorate islets.
“Our goal is to keep beta cells happy,” Roep said. “So we will work on new forms of therapy to correct the autoimmune response against islets and hopefully also prevent development of type 1 diabetes during anti-cancer therapy.”
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