Diabetes develops when beta cells are damaged or destroyed, preventing the body from producing enough insulin, the hormone that regulates blood sugar. Photo by Pavel Danilyuk/Pexels
Argentine scientists have identified a mechanism that allows pancreatic beta cells, which produce insulin, to become resistant to damage. The finding opens the door to new therapies for diabetes, a disease that affects more than 500 million people worldwide.
The discovery was made by researchers at the Immuno-Endocrinology, Diabetes and Metabolism Laboratory at CONICET-AUSTRAL, led by Marcelo J. Perone. The team showed that these cells can adapt to moderate stress and withstand attacks that would normally destroy them.
Diabetes develops when beta cells are damaged or destroyed, preventing the body from producing enough insulin, the hormone that regulates blood sugar. In Type 1 diabetes, an autoimmune attack wipes them out; in Type 2, stress caused by obesity, chronic inflammation and high glucose levels gradually wear them down.
The study is significant because it shows how the cells can be “trained” with low levels of inflammation to resist greater harm, offering a foundation for therapies that protect them and slow the progression of the disease.
According to the authors, the findings published in the journal Cell Death & Disease makes it possible to design treatments that protect beta cells and help manage a metabolic disease with major health and economic impacts worldwide.
The work stems from nearly 20 years of research by Perone’s team, which had already identified key mechanisms involved in the dysfunction of insulin-producing cells.
With biochemical experiments carried out by CONICET fellow Carolina Sétula, the researchers advanced their understanding of how these cells function and how they respond to damage.
Regarding their ability to resist damage, Perone told UPI that beta cells are highly sensitive to inflammatory agents such as cytokines, particularly interleukin-1 beta.
“Its levels rise sharply during inflammation and infections,” he said.
The team asked why these cells have so many receptors for a molecule that can damage them.
“Through in vitro experiments we showed that the effect of interleukin-1 beta, long considered toxic for beta cells, depends on the concentration. When exposed to very low doses, the cells become resistant to high concentrations that would normally kill them,” he said.
In other words, the effect of interleukin-1 beta depends on the dose. At high levels, it is toxic, but at low levels it acts like a kind of vaccine. When the cells are first exposed to low doses, they adapt and later withstand high doses without dying.
Perone added that for many years researchers believed IL-1 only caused beta-cell death, but it is now clear that it plays an important physiological role by helping these cells adapt under adverse conditions.
“Our study shows that low doses of the cytokine IL-1β, once considered harmful, can protect insulin-producing cells from inflammation through a process called hormesis,” he said.
Hormesis is a biological phenomenon in which a low dose of a potentially harmful agent produces a beneficial effect, while high doses are toxic. “It is an adaptive response that strengthens an organism or a cell against stress,” Perone said.
He said the finding opens the possibility of new therapies to preserve beta-cell function in Type 1 and Type 2 diabetes, slow the progression of the disease, improve quality of life for millions and reduce medical costs.
“For now, our results offer a better understanding of the beta cell and suggest that interventions could be developed to make these cells more resilient to the types of damage seen in diabetes,” he said.
He noted that the project is still in an early stage and that clinical application will take time. The team is now studying which internal mechanisms increase beta-cell resistance to inflammatory stress as they seek to identify targets for a possible drug treatment.
