US-Israeli scientists uncover how insulin cells keep up with age … and what happens when they can’t

A team of Israeli and U.S. scientists has found that the body’s insulin-producing cells continuously adjust over time to keep blood sugar stable, raising the possibility of new treatments that could delay or prevent Type 2 diabetes, the Hebrew University of Jerusalem announced on Tuesday.

Type 2 diabetes affects more than half a billion people worldwide and is strongly associated with aging and lifestyle factors. It develops when the body becomes resistant to insulin — the hormone that helps move sugar from the bloodstream into cells for energy — forcing the pancreas to produce more insulin to compensate. The disease is typically treated through a combination of lifestyle changes and medications aimed at improving insulin sensitivity and maintaining healthy blood sugar levels.

Despite the prevalence of Type 2 diabetes, scientists still do not fully understand how pancreatic beta cells gradually lose their ability to produce insulin effectively over time. As people age, the body naturally becomes more resistant to insulin, yet most individuals are still able to maintain stable blood sugar levels for decades.

The new Israeli-U.S. study suggests beta cells cope with this growing demand through epigenetic changes—chemical modifications that affect how genes are activated without altering the DNA sequence itself.

The research, led by Dr. Dana Avrahami-Tzfati of the Hebrew University of Jerusalem in collaboration with Dr. Elisabetta Manduchi and professor Klaus Kaestner of the University of Pennsylvania, examined how insulin-producing beta cells respond throughout the human lifespan and how those responses differ in individuals with Type 2 diabetes.

The findings, published in the peer-reviewed journal Nature Metabolism, were based on detailed genetic regulatory data from the Human Pancreas Analysis Program.

Researchers found that in healthy individuals, beta cells undergo a gradual age-related process known as DNA demethylation in regions of the genome linked to insulin production. The process appears to help the cells maintain insulin-producing function over decades.

By contrast, other pancreatic cells, known as alpha cells, followed a different pattern, showing slight increases in methylation, suggesting that different pancreatic cell types age differently.

From adaptations to exhaustion

In individuals with Type 2 diabetes, researchers observed significantly increased DNA demethylation in beta cells compared to non-diabetic individuals. The findings suggest that the same compensatory process seen in healthy aging becomes intensified under chronic metabolic stress. While the response may initially help maintain insulin production, researchers said it eventually becomes unsustainable, contributing to the gradual exhaustion of beta cells and disease progression.

“We found that aging in the pancreas is not just a process of decline, but one of constant adjustment,” said Avrahami-Tzfati. “Beta cells are essentially running a marathon to keep blood sugar stable. They can do this remarkably well for decades—but in Type 2 diabetes, that marathon turns into a sprint.”

The findings suggest that Type 2 diabetes may involve not a sudden collapse of beta cells, but the gradual breakdown of a long-term biological coping process that normally helps maintain glucose balance throughout life.

“This study shows that mechanisms helping beta cells adapt throughout life may also become overactivated under chronic stress,” said Kaestner. “Understanding this balance points to future research aimed at preserving beta-cell function and slowing disease progression.”

The study suggests that epigenetic changes in beta cells could become a future therapeutic target in Type 2 diabetes. By stabilizing DNA methylation patterns, researchers may eventually be able to help beta cells maintain their function and avoid the chronic overwork that can lead to failure.

The findings also point to earlier intervention strategies aimed at reducing long-term stress on beta cells before damage becomes irreversible. In addition, the research raises the possibility of using epigenetic biomarkers to identify when beta cells shift from healthy adaptation to harmful strain.