Chronic stress doesn’t just affect your mood — it may also wear out the very cells that keep your blood sugar in check.
New research from Osaka Metropolitan University has uncovered a key gene that makes insulin-producing cells more vulnerable to damage when exposed to poor dietary conditions. The study, published in the Journal of Biological Chemistry, identifies a stress-responsive gene called REDD2 as a major driver of pancreatic β-cell dysfunction, a critical step in the development of type 2 diabetes.
“We found that suppressing REDD2 expression protects β-cells from damage, even under stress from overeating, preventing the onset of diabetes,” said lead author Dr. Naoki Harada.
β-cells are the pancreas’s insulin factories, responsible for producing the hormone that helps regulate blood sugar. But under stress caused by too much sugar, fat or inflammation, these cells begin to falter. That stress, known as oxidative stress, is a major trigger in the progression to type 2 diabetes.
To find out what pushes β-cells over the edge, the researchers focused on REDD2, a gene that normally helps cells respond to stress but can backfire when overactivated. In lab models and animal studies, REDD2 levels spiked under high-glucose and high-fat conditions. This led to:
More β-cell death
Lower insulin production
Disruption of mTORC1, a key pathway involved in cell growth and survival
However, when REDD2 was turned off, the results were striking: mice fed a high-fat diet had better blood sugar control, more surviving insulin-producing cells and stronger insulin output, even under conditions that usually lead to diabetes.
The team also examined human pancreatic cells and found similar signs that REDD2 may play a harmful role in people as well.
“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.
While the research is still in early stages, it adds important insight into how metabolic stress from diet and cell-level genetics interact to drive disease. It also highlights the importance of lifestyle factors, not just genetics, in shaping long-term health.
This study was supported by grants from the Japan Society for the Promotion of Science and the Japan Agency for Medical Research and Development.