Stress does no one — not even your insulin-producing cells — any good.

Researchers from Osaka Metropolitan University have identified a gene that, when activated by metabolic stress, damages pancreatic β-cells — the cells responsible for insulin production and blood sugar control — pushing them toward dysfunction. The findings highlight a promising new target for early intervention in type 2 diabetes.

While many factors can contribute to type 2 diabetes, lifestyle, especially diet, plays a major role in its onset. Genetics matter, but poor eating habits can greatly increase the risk of developing what is now often called a “silent epidemic.”

“Type 2 diabetes occurs when pancreatic β-cells, which secrete insulin to regulate blood glucose, become impaired due to prolonged stress caused by poor dietary habits, a condition known as oxidative stress,” said Naoki Harada, an associate professor at Osaka Metropolitan University’s Graduate School of Agriculture and lead author of this study.

But what, exactly, wears out these vital cells?

Looking for an answer, the team turned to a stress-responsive gene called REDD2. These types of genes are activated when cells are under pressure and are meant to assist with the cells’ stress-coping strategies. This, however, sometimes backfires.

“We observed that increased expression of this gene damages β-cells, which in turn leads to reduced insulin secretion and the onset of diabetes,” Harada said.

The team found that REDD2 activity surged when β-cells were exposed to high levels of glucose, fatty acids, and STZ — a chemical commonly used to model diabetes in lab settings. When REDD2 levels were suppressed, the β-cells survived better and retained their function. Conversely, overactive REDD2 led to increased cell death and disruption of a key cellular growth pathway known as mTORC1.

Further experiments in culture cells and model mice also demonstrated that REDD2-deficient mice had better blood sugar control when fed a high-fat diet or exposed to diabetes-inducing chemicals. These mice also had greater numbers of healthy β-cells and produced more insulin. Data analysis of human islets supports the negative impacts of REDD2 on β-cell mass and insulin secretion capacity.

“We found that suppressing REDD2 expression protects β-cells from damage, even under stress from overeating, preventing the onset of diabetes,” Harada said.

The discovery of REDD2’s role as a key player in β-cell damage opens new possibilities for early diagnosis and treatment of type 2 diabetes.

“We hope REDD2 can serve as a diagnostic marker for type 2 diabetes and pave the way for new drugs or functional foods that target it,” Harada said.

The study was published in the Journal of Biological Chemistry.

Conflict of interest
The authors declare that they have no conflicts of interest with the contents of this article.

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