RESEARCH from The Jackson Laboratory reveals that pancreatic cells have a stress tolerance limit, which, when exceeded by factors like inflammation and hyperglycemia, can lead to type 2 diabetes.
The study highlights a correlation between genetic variations that elevate diabetes risk and how pancreatic cells respond to stress.
Specifically, researchers focused on how islet beta cells react to two types of molecular stress: endoplasmic reticulum (ER) stress and cytokine stress. They found that sustained stress can overwhelm these cells, impairing insulin production or causing cell death.
The team, led by Michael L. Stitzel and Dugyu Ucar, examined over 5,000 genes in healthy human islet cells subjected to chemical stressors.
They discovered significant changes in gene expression and DNA regulatory regions, particularly noting that 86 regions linked to genetic variants in diabetes-prone individuals were affected by stress.
This suggests that genetic predisposition may compromise the ability of islet cells to cope with stress, potentially increasing diabetes risk.
Stitzel’s research also pinpointed the MAP3K5 gene, which, when overexpressed, led to higher islet cell death under stress.
Conversely, blocking this gene increased cell resilience. Promisingly, Selonsertib, a drug targeting MAP3K5, is in clinical trials and may offer preventive benefits for those at risk of diabetes.
The findings aim to pave the way for new therapeutic strategies that enhance islet cell resilience and potentially prevent diabetes onset in susceptible individuals. SOURCE: ANI
