Researchers know that type 1 diabetes (T1D) occurs when the immune system mistakenly attacks and destroys insulin-producing beta cells. This leaves the body unable to self-regulate blood glucose levels because it produces little or no insulin on its own. What scientists have been striving to understand is what causes the body to destroy these cells in the first place.
A recent study found that the beta cells themselves may play a role in signaling the attack. The insulin-producing cells may be sending out signals that increase M1 macrophages that cause inflammation and the resulting cell destruction. The M2 macrophages that reduce inflammation and help repair tissue are not as heavily expressed.
The researchers looked specifically at Ca2+-independent phospholipase A2beta (iPLA2beta) enzymes and the resulting iPLA2beta-derived lipids (idles) and how they are activated by beta cells. The idols either stimulate M1 macrophages or M2 macrophages depending on the active signaling pathways.
The study involved two sets of mice – one group that had no iPLA2beta expression (knockout mice), and one group with overexpression of iPLA2beta. Researchers found that even when M1 macrophage activation was induced, the knockout mice experienced an increase in M2 macrophages and a reduced inflammatory state. The mice that had overexpression of iPLA2beta, on the other hand, experience an increase in M1 macrophages and inflammatory eicosanoids.
According to Sasanka Ramanadham, Ph.D., research co-lead, “To our knowledge, this is the first demonstration of lipid signaling generated by beta cells having an impact on an immune cell that elicits inflammatory consequences. We think lipids generated by beta cells can cause the cells’ own death.”
As scientists continue to learn more about lipid signaling and the potential role it plays in the development of type 1 diabetes, this could lead to improved methods of delaying or preventing onset or progression of the disease. This is yet another approach that researchers are taking to understand as much as they can about how and why T1D develops and how to better manage the disease.
It is this type of research that opens doors to advancements toward preventing or curing type 1 diabetes. Diabetes Research Connection (DRC) supports early-career scientists pursuing novel, peer-reviewed research studies focused on improving diagnosis, treatment, and prevention of T1D as well as improving quality of life for individuals living with the disease and one day finding a cure. Ensuring researchers receive necessary funding for their projects is critical. To learn more about current projects and support these efforts, visit https://diabetesresearchconnection.org.