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Researchers describe changes in pancreatic beta cells during the onset of type 1 diabetes

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AAV8-mediated Mettl3 overexpression in NOD mouse β cells in vivo delays T1D progression. credit: natural cell biology (2024). DOI: 10.1038/s41556-024-01368-0

Approximately 8 million people worldwide have type 1 diabetes (T1D). T1D is a chronic autoimmune disease in which the body attacks and destroys its own insulin-producing beta cells (pronounced “beta”) in the pancreas, causing insulin and insulin deficiency. Masu. Inability to regulate blood sugar levels. It is unclear why the body suddenly recognizes its own beta cells as enemies. Some evidence suggests that environmental factors, such as viral infections, may trigger the development of T1D, and other evidence suggests that genetics may also play a role.

A groundbreaking study by researchers at the Joslin Diabetes Center sheds new light on specific changes that beta cells undergo during the onset of T1D. Their findings—published in natural cell biology– Provide new avenues for targeted intervention against chronic autoimmune conditions.

“In the field of type 1 diabetes, research has primarily focused on understanding the immune component, but our work argues that beta cells play an important role,” said Margaret A. said Rohit N. Kulkarni, MD. Congleton Chair and Co-Head of the Pancreatic Islet and Regenerative Biology Section at the Joslin Diabetes Center.

“Our findings suggest that beta cells may trigger important events that promote abnormal autoimmune mechanisms. This is a paradigm-changing approach.”

In a series of experiments using a mouse model of T1D and beta cells from humans with established T1D, Kulkarni and colleagues uncovered a complex cascade of biochemical steps, called signaling pathways, that control the innate immune response during disease onset. I made it. T1D’s.

The researchers identified one pathway that influences the immune properties of beta cells, acting like a control switch that distinguishes beta cells from friend or foe to the body. You can imagine these control switches as small tags.

Researchers focused on one particular tag, called N6-methyladenosine (m6A), which plays a key role in the beta cell response during the onset of T1D. By adjusting these regulatory switches, the researchers were able to influence the levels of key proteins along this pathway, significantly slowing disease progression in a T1D mouse model.

Dario F. de Jesús, M.A., Ph.D., lead author of the study and a researcher in Kulkarni’s lab, identified METTL3, an enzyme important in regulating beta-cell antiviral defenses.

At later stages of T1D, METTL3 levels were low, suggesting that high METTL3 levels protect β-cells from dysfunction. The research team was able to slow disease progression by boosting METTL3 production in a mouse model.

“This finding suggests that interventions that increase METTL3 levels are a potential strategy to protect beta cells and slow the progression of type 1 diabetes,” said de Jesús, who is also an instructor in medicine at Harvard Medical School. said.

Taken together, these several lines of evidence reveal a clearer picture of the still-mysterious immune phenomena surrounding the development of T1D, including new mechanisms available for beta-cell protection. They also demonstrated that the enzyme METTL3 may promote β-cell survival and function during disease progression.

“It’s worth noting that there are commercially available compounds in this pathway that are used in connection with other diseases,” said Kulkarni, who is also a professor of medicine at Harvard Medical School.

“Although the targets are different, it is an approach that has been proven to be effective. The next steps will focus on identifying specific molecules and pathways that can be exploited to enhance beta-cell protection. ”

For more information:
Redox regulation of the m6A methyltransferase METTL3 in beta cells controls innate immune responses in type 1 diabetes. natural cell biology (2024). DOI: 10.1038/s41556-024-01368-0 www.nature.com/articles/s41556-024-01368-0

Provided by Joslin Diabetes Center

Quote: Shifting focus: Researchers describe changes in pancreatic beta cells during the onset of type 1 diabetes (February 26, 2024) https://medicalxpress.com/news/2024-02-shifting-focus-pancreatic- Retrieved March 1, 2024 from cells-onset.html

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