Mitochondrial Stress Disrupts Insulin Production in Diabetes, Study Finds
TEHRAN (Tasnim) – Researchers at the University of Michigan have identified how mitochondrial dysfunction impairs insulin-producing pancreatic β-cells in diabetes, but findings suggest that reversing the damage could restore their function.
Mitochondria generate the energy necessary for cells to function. However, defects in these organelles are linked to diseases such as type 2 diabetes, where patients either fail to produce enough insulin or cannot effectively use the insulin their pancreas produces to regulate blood sugar levels.
Previous studies have shown that diabetic patients’ β-cells have abnormal mitochondria and insufficient energy production, but the reasons behind this dysfunction remained unclear.
In a study published in Science, researchers used mice to demonstrate that damaged mitochondria activate a stress response that hinders β-cell maturation and function.
“We wanted to determine which pathways are important for maintaining proper mitochondrial function,” said Emily M. Walker, Ph.D., research assistant professor of internal medicine and first author of the study.
The team disrupted three key components essential for mitochondrial function: mitochondrial DNA, a pathway for removing damaged mitochondria, and another that maintains a healthy mitochondrial population in the cell.
“In all three cases, the exact same stress response was turned on, which caused β-cells to become immature, stop making enough insulin, and essentially stop being β-cells,” Walker said.
The researchers confirmed their findings in human pancreatic islet cells, suggesting a broader relevance of mitochondrial dysfunction in diabetes.
Mitochondrial Dysfunction Affects Multiple Cell Types
Their results led the team to investigate other cell types affected by diabetes.
“Diabetes is a multi-system disease—you gain weight, your liver produces too much sugar, and your muscles are affected. That’s why we wanted to look at other tissues as well,” said Scott A. Soleimanpour, M.D., director of the Michigan Diabetes Research Center and senior author of the study.
Repeating their experiments in liver and fat-storing cells, the researchers observed the same stress response, leading to impaired maturation and function in both cell types.
“Although we haven’t tested all possible cell types, we believe that our results could be applicable to all the different tissues that are affected by diabetes,” Soleimanpour said.
Reversing Mitochondrial Damage May Restore β-Cell Function
Despite mitochondrial dysfunction, the researchers found that affected cells did not undergo cell death, raising the possibility that reversing the damage could restore normal function.
To test this, they treated mice with a drug called ISRIB, which blocks the stress response. After four weeks, the β-cells regained their ability to control glucose levels.
“Losing your β-cells is the most direct path to getting type 2 diabetes. Through our study, we now have an explanation for what might be happening and how we can intervene and fix the root cause,” Soleimanpour said.
The team is now working to further understand the disrupted cellular pathways and aims to replicate their findings in cell samples from diabetic patients.
