Diabetes & Stress: Gene Impact on Cell Health
- Pancreatic cells, like any living tissue, have their limits.
- Now, researchers at The Jackson Laboratory (JAX) have found a link between DNA sequence variations and the ability of pancreatic cells to manage molecular stress.
- Stitzel, associate professor at JAX, said the goal is to find new ways to prevent and treat type 2 diabetes by targeting genes and pathways affected in susceptible...
discover the critical link between cellular stress and diabetes risk. New research unveils how specific DNA changes impact the ability of pancreatic cells to handle stress, possibly leading to cell failure and the onset of type 2 diabetes. The study highlights dozens of genes that influence this process,offering valuable insight into how genetics play a role in diabetes,and which genes could be targeted to improve patient outcomes. Scientists are already exploring drugs focused on one key gene identified in the study, with promising results in clinical trials. The team found separate stress pathways play a role in diabetes, thus offering new direction in gene therapy. Stay informed with News Directory 3. Discover whatS next …
Genes Linked to pancreatic Cell Stress Response, Impacting Diabetes Risk
Updated june 23, 2025
Pancreatic cells, like any living tissue, have their limits. When overwhelmed by stressors such as inflammation and high blood sugar, these cells can break down, contributing to the progress of type 2 diabetes.
Now, researchers at The Jackson Laboratory (JAX) have found a link between DNA sequence variations and the ability of pancreatic cells to manage molecular stress. The study, focusing on type 2 diabetes, suggests that individuals with specific DNA changes may have insulin-producing cells more vulnerable to failure or death when exposed to stress and inflammation.
Michael L. Stitzel, associate professor at JAX, said the goal is to find new ways to prevent and treat type 2 diabetes by targeting genes and pathways affected in susceptible individuals. He co-authored the study with JAX professor Duygu Ucar. The findings offer insights into these genes and pathways.
The research highlights dozens of genes connecting cell stress and diabetes risk. One identified gene is already being explored as a drug target for diabetes complications.
Living cells activate protective responses when facing challenges like damage or inflammation. However, sustained stress can overwhelm cells, causing them to slow down or die. In pancreatic islet beta cells, endoplasmic reticulum (ER) stress and cytokine stress have been linked to type 2 diabetes.ER stress occurs when cells are overwhelmed by protein production demands, while cytokine stress involves excessive inflammatory signals from the immune system.
Both types of stress can lead islet beta cells to stop producing insulin or die. Stitzel and his team investigated the genes and proteins used by islet cells to respond to both ER stress and cytokine stress.
Stitzel said that while previous research focused on molecular pathways in healthy islet cells, their study examined pathways important when cells are under stress and how diabetes-linked DNA sequence changes effect them.
The team exposed healthy human islet cells to compounds inducing ER stress or cytokine stress. They then tracked changes in RNA molecule levels and DNA packing within the cells, indicating which genes and regulatory elements were being used.
Working with Ucar, a computational biologist, the scientists found that over 5,000 genes, nearly a third of those expressed by healthy islet cells, changed expression in response to ER stress or cytokine stress. Many were involved in protein production, crucial for insulin production. Most genes were involved in only one stress response,suggesting seperate stress pathways play a role in diabetes.
Additionally, about one in eight regulatory DNA regions typically used in islet cells were altered by stress. Eighty-six of these regions contained genetic variants previously linked to type 2 diabetes risk.
Stitzel said this suggests that people with these genetic variants may have islet cells that respond worse to stress. He added that while surroundings factors like diabetes and obesity can trigger type 2 diabetes, genetics can increase susceptibility.
Stitzel hopes the findings will lead to new drugs to prevent or treat diabetes by making islet cells more resilient to stress, addressing the underlying causes of type 2 diabetes.
Researchers focused on the MAP3K5 gene, altered by both ER stress and cytokine stress. Studies in mice showed that this gene affects islet beta cell death. Higher levels of MAP3K5 led to more islet beta cells dying in response to ER stress. Blocking MAP3K5, conversely, made islet cells more resilient.
Early studies of selonsertib, a drug targeting MAP3K5, suggest it could reduce the risk of severe diabetes complications. The new results suggest the drug might also prevent diabetes in at-risk individuals by helping islet cells function under cellular stress.
Stitzel said it is exciting that this therapeutic is already in clinical trials, but more work is needed to understand whether the drug might be leveraged in primary prevention.
What’s next
Further research will explore how to leverage these findings to develop targeted therapies that enhance pancreatic cell resilience and prevent the onset of type 2 diabetes in at-risk individuals.