March 1, 2024
News Release

PNNL Scientists Help Pinpoint Molecular Switch Active in Type-1 Diabetes

Key protein offers protection to insulin-producing cells

Photo of Wei-Jun Qian

Wei-Jun Qian is a leader in detecting and understanding redox reactions, which play a role in basic processes in energy and the environment as well as human health.

(Photo by Andrea Starr | Pacific Northwest National Laboratory)

RICHLAND, Wash.—Scientists trying to understand Type-1 diabetes have long focused on our immune system. After all, symptoms stem from an autoimmune attack, when our own immune cells attack and kill insulin-producing cells known as beta cells in our pancreas.

But a paper published this week in Nature Cell Biology points to the target of this assault as playing a key role in their own destruction. Researchers from the Joslin Diabetes Center in Boston, together with a team at Pacific Northwest National Laboratory and others, demonstrated that beta cells have a key molecular mechanism that protects them.

The work focused on METTL3, a protein more active in people and in mice in the early stages of Type-1 diabetes but whose activity diminishes as the disease progresses. When the team ramped up the protein’s activity in mice, the change reduced the autoimmune attack and slowed the disease’s progression.

The PNNL team pinpointed the specific amino acid residues that are subjected to a type of molecular modification that changes the protein—a redox reaction, one type of chemical switch that can turn protein activity on or off. Such reactions are central to human health and to environmental processes related to energy, climate and related areas. In this study, the findings give scientists critical information to help guide further studies aimed at protecting insulin-producing cells.

PNNL scientists Xiaolu Li and Matthew Gaffrey worked with Wei-Jun Qian, a leader in detecting such redox modifications, to make the finding.

The senior author is Harvard scientist Rohit Kulkarni, with whom Qian has collaborated for more than 15 years. The work was funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others. Some measurements were made at the Environmental Molecular Sciences Laboratory, a Department of Energy, Office of Science user facility located at PNNL. More details are available from the Joslin Diabetes Center.


About PNNL

Pacific Northwest National Laboratory draws on its distinguishing strengths in chemistry, Earth sciences, biology and data science to advance scientific knowledge and address challenges in sustainable energy and national security. Founded in 1965, PNNL is operated by Battelle for the Department of Energy’s Office of Science, which is the single largest supporter of basic research in the physical sciences in the United States. DOE’s Office of Science is working to address some of the most pressing challenges of our time. For more information, visit For more information on PNNL, visit PNNL's News Center. Follow us on Twitter, Facebook, LinkedIn and Instagram.