Key points from article :
Scientists from the University of Michigan have found that damaged mitochondria in pancreatic β-cells activate the integrated stress response (ISR), leading to cell malfunction and loss of identity.
They analyzed pancreatic islets from type 2 diabetes patients and discovered that β-cells had lower mitochondrial DNA, reduced gene expression, and impaired mitophagy, while other cells were unaffected. To explore this further, they engineered three mouse models with different mitochondrial defects, all of which triggered ISR and caused β-cells to lose their specialized function.
Similar effects were observed in liver and fat cells, suggesting that mitochondrial dysfunction may contribute to multiple metabolic issues in diabetes. Treating mouse cells with an ISR inhibitor, ISRIB, restored β-cell identity by blocking retrograde ISR signaling.
Published in Science, the study suggests that targeting mitochondrial stress pathways could be a potential therapeutic strategy for diabetes.
