Researchers identify new target for potential type 1 diabetes treatment

October 18, 2018 | by Katie Neith

Thurmond-Debbie Debbie Thurmond, Ph.D.
Although the exact cause of type 1 diabetes remains a mystery, the disease results from the destruction of insulin-producing islet beta cells, which is often due to a patient’s own immune system mistakenly attacking the cells. In searching for a cure for type 1 diabetes, researchers are exploring ways to keep the immune system stable and islet beta cells healthy. Recently a team of researchers led by City of Hope scientists identified a new potential target for doing exactly that and keeping type 1 diabetes at bay. Their results were published in a recent issue of the journal Diabetes.

“We have found a protein called STX4 to be a new factor that can protect islet beta cells from type 1 diabetes-related stressors, hence preserving the body’s own beta cells and deterring the onset of type 1 diabetes,” said Debbie Thurmond, Ph.D., professor and chair of the Department of Molecular and Cellular Endocrinology in the Diabetes & Metabolism Research Institute at City of Hope, and the Ruth B. & Robert K. Lanman Chair in Gene Regulation and Drug Discovery Research. Thurmond created the study outlined in the paper and is also the corresponding author of the publication.
 
STX4 occurs naturally in the body, but immune system changes can lead to its loss, which correlates with an increased susceptibility to type 1 diabetes-related stressors.
 
Building on previous knowledge that STX4 enrichment in islet grafts improved transplant success, the researchers used animal models and human islets to test its efficacy against pro-inflammatory stressors. They found that adding more STX4 to their models provided protection from these stressors for beta cells.
 
“Now that we know STX4 enrichment can prevent the failure of beta cells, there is the potential that this can be used as a strategy to prevent type 1 diabetes,” said Thurmond.
 
She says it may even be useful to protect the beta cells still in existence in type 1 diabetes patients, and even to “wake up” reservoirs of dormant beta cells.
 
“Importantly, as beta cell failure is a major hallmark in the conversion from pre- to type 2 diabetes, STX4 enrichment also holds potential for preventing type 2 diabetes,” Thurmond added.
 
Moving forward, the major emphasis of additional research will be on how to best enrich STX4 in the body by figuring out how to get it into cells, or how to coerce the cells to start making more of it on their own, said Thurmond.
 
“In addition, we need to learn in greater detail how it provides protection to the beta cells, and this will inform on how we can mimic this wonderful action via therapeutic design,” she said.
 
The study, outlined in the paper, “Syntaxin 4 expression in pancreatic β-cells promotes and protects functional β-cell mass,” was supported by City of Hope’s Wanek Family Project for Type 1 Diabetes and by grants from the National Institutes of Health and the Juvenile Diabetes Research Foundation. Additional City of Hope authors include Eunjin Oh, Ph.D., assistant research professor in the Department of Molecular and Cellular Endocrinology, and Miwon Ahn, Ph.D., staff scientist, both of whom are members of Thurmond’s lab, and Bart O. Roep, Ph.D., the Chan Soon-Shiong Shapiro Distinguished Chair in Diabetes and the founding chair of the Department of Diabetes Immunology within the Diabetes & Metabolism Research Institute at City of Hope. Scientists from the University of Illinois at Chicago and Duke also contributed to the work.
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