Out of the box approach to type 1 treatment

Monday, 13 January 2020

New research out of the US has identified a protein in mice with type 1 diabetes that is providing a new target for prevention and treatment in people. Because type 1 diabetes is incurable and has serious lifelong health consequences, prevention is a major research goal.

The key to the new study, published in the journal Cell Metabolism, is a technique called mass spectrometry, which can comprehensively detect proteins that are found at extremely low levels in the body, but can have large effects on health.

About the research

The multidisciplinary research team of physicians and biochemists used a new strategy to pinpoint proteins in beta cells, a subset of pancreatic islets that increase or decrease in response to immune system attack. Beta cells normally regulate blood glucose levels in the pancreas. In people susceptible to type 1 diabetes these cells are slowly destroyed by the body’s own immune system. So, the researchers focused on how islets respond to inflammation.

The researchers treated human pancreatic islets with substances produced by the body and thought to be involved in the development of diabetes. They identified a total of 11,324 proteins, with 387 affected by the treatment. Of these 387, they narrowed their focus to one: growth differentiation factor 15 (GDF15).

Ernesto Nakayasu, a biomedical scientist and co-lead author of the study, said “We wanted to identify proteins that can intervene in the diabetes disease process. We became interested in GDF15 because the protein level was suppressed by 70 percent after treatment.”

What is GDF15?

GDF15 is known for its protective effects in different types of cells in the human body but it had never been studied in islets. When the researchers measured levels of GDF15 in pancreas tissue from people with diabetes, they found the protein was depleted in their malfunctioning islet cells.

But the key piece of evidence emerged when the scientists treated non-obese mice with diabetes using GDF15, and it reduced development of diabetes by 53%. Non-obese mice with diabetes are a common model for testing type 1 treatments because they spontaneously develop autoimmune diabetes with many similarities to the human disease.

“We hypothesized that reduced GDF15 was not a good thing for islet survival, and indeed that was the case,” said Raghu Mirmira, a principal investigator on the study.

“This work opens the way for us to consider these sorts of ‘islet protective factors’ as therapies to prevent or reverse type 1 diabetes.”

“This approach differs substantially from current thinking that targets the immune system. While GDF15 may be one new therapy, we identified other proteins that may work in conjunction with GDF15, so this work really represents a treasure-trove of information that can be mined for new therapies,” said Mirmira.

What’s next?

The researchers are now working on the idea that low levels of GDF15 in islets may somehow be playing a proactive role in instigating the autoimmune attack that ultimately kills them.

This thinking is somewhat counterintuitive in the type 1 diabetes field, but it is this kind of out-of-the-box thinking that may lead to therapies we never thought of previously.

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