Understanding How Pancreatic Cell Stress Leads to Type 2 Diabetes
Insights from The Jackson Laboratory
Pancreatic cells, like human cells, can only handle so much stress before they start to break down. When these cells are overstimulated by stressors like inflammation and high blood sugar, it can lead to type 2 diabetes. Researchers at The Jackson Laboratory (JAX) have found that the ability of pancreatic cells to handle stress is linked to DNA variations that increase diabetes risk.
Michael L. Stitzel, an associate professor at JAX, along with JAX professor Dugyu Ucar, published a study in Cell Metabolism. They aim to develop new ways to prevent and treat type 2 diabetes by targeting genes and pathways affected in those most at risk. Their research highlights dozens of genes connecting cell stress to diabetes risk, including one being studied as a drug target.
When cells face challenges like damage or inflammation, they activate protective responses. However, prolonged stress can overwhelm cells, causing them to slow down or die. In the pancreas, two types of stress can lead islet beta cells to stop producing insulin or die. Stitzel’s team studied how islet cells respond to ER stress and cytokine stress, finding that over 5,000 genes change their expression in response to these stresses.
Importantly, 86 regulatory DNA regions, previously linked to diabetes risk, were altered by stress. This suggests that people with these genetic variants may have islet cells that respond worse to stress. Stitzel hopes this research will lead to new drugs to make islet cells more resilient to stress.
One gene, MAP3K5, was found to affect islet beta cell death. Blocking MAP3K5 made cells more resilient to stress. A drug targeting MAP3K5, Selonsertib, is in clinical trials and may help prevent diabetes in at-risk individuals by keeping islet cells functioning under stress.
Doubts Revealed
Pancreatic Cell -: Pancreatic cells are special cells in the pancreas, an organ in our body that helps with digestion and controls blood sugar levels. These cells produce insulin, a hormone that helps manage sugar in the blood.
Type 2 Diabetes -: Type 2 diabetes is a condition where the body doesn’t use insulin properly, leading to high blood sugar levels. It is often related to lifestyle factors like diet and exercise.
The Jackson Laboratory -: The Jackson Laboratory is a research institute in the United States that studies genetics and diseases. They work to understand how genes affect health and develop new treatments.
DNA Variations -: DNA variations are small differences in our genetic code that can affect how our bodies work. Some variations can increase the risk of diseases like diabetes.
Genes and Pathways -: Genes are parts of our DNA that tell our bodies how to function. Pathways are series of actions among molecules in a cell that lead to a certain product or change in the cell.
MAP3K5 -: MAP3K5 is a gene that plays a role in cell stress and death. It can affect how cells respond to stress, which is important in diseases like diabetes.
Selonsertib -: Selonsertib is a drug being tested to see if it can help prevent diabetes by blocking the effects of the MAP3K5 gene. It is still in the trial phase, meaning scientists are studying if it works and is safe.
