Shifting focus: Investigators describe changes to pancreatic beta cells at onset of type 1 diabetes

Key Takeaways

• Researchers have identified a pathway that influences the immune characteristics of beta cells, i.e., whether they are identified by the immune system as friend or foe.
• The findings offer new avenues for targeted interventions for type 1 diabetes.

About eight million people live with type 1 diabetes (T1D) worldwide, a chronic autoimmune condition in which the body attacks and destroys its own insulin-producing beta cells in the pancreas, leading to a lack of insulin and inability to regulate blood sugar. It’s not known why the body suddenly perceives its own beta cells as the enemy; some lines of evidence suggest environmental factors such as viral infections may trigger the onset of T1D, others suggest genetics may also play some role. Groundbreaking research by investigators at Joslin Diabetes Center sheds new light on the specific changes beta cells go through at the onset of T1D. “In the field of type 1 diabetes, research has largely focused on understanding the immune component, but our study argues that the beta cell is a significant player,” said Rohit N. Kulkarni, M.D., Ph.D. “Our findings suggest that the beta cell could be initiating key events which then promote the autoimmune mechanism to go awry. It’s a paradigm shifting approach.” The findings—published in Nature Cell Biology—offer new avenues for targeted interventions for the chronic autoimmune condition.

In a series of experiments with beta cells taken from a mouse model of T1D, as well as from humans with established T1D, Kulkarni and colleagues teased out the complex cascade of biochemical steps called a signaling pathway that controls the innate immune response at the onset of T1D. The team identified one pathway that influences the immune characteristics of beta cells, which act like control switches that identify them as friend or foe to the body.

The team then discovered that these control switches play a vital role in the response of beta cells during T1D onset. By adjusting the control switches, the researchers were able to influence the levels of a crucial protein along this pathway, leading to a notable delay in the progression of the disease in a mouse model of T1D.

“It is notable that this pathway has commercially available compounds that have been used in the context of other diseases,” said Kulkarni.  “While it’s a different target, it’s an approach which has been shown to work. Among our next steps, we will focus on identifying specific molecules and pathways that can be harnessed to enhance protection of the beta cell.”

Edited by Miriam Kaplan, PhD

Source: Joslin Diabetes Center, Medical Xpress, February 26, 2024; see source article