PNNL

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.