How Mitochondrial Defects Impair Insulin Production in Type 2 Diabetes? Study Sheds Light - Video

In a study published in Science, researchers at the University of Michigan used mice to show that dysfunctional mitochondria trigger a response that affects the maturation and function of insulin-producing pancreatic β-cells.

Mitochondrial defects are associated with the development of diseases such as type 2 diabetes. Patients who suffer from this disorder are unable to produce enough insulin or use the insulin produced by their pancreas to keep their blood sugar at normal levels.

Researchers damaged three components that are essential for mitochondrial function: their DNA, a pathway used to get rid of damaged mitochondria, and one that maintains a healthy pool of mitochondria 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,” said Emily M. Walker, Ph.D, a research assistant professor of internal medicine and first author of the study.

“Our results demonstrate that the mitochondria can send signals to the nucleus and change the fate of the cell.”

The researchers also confirmed their findings in human pancreatic islet cells. The team repeated their mouse experiments in liver cells and fat-storing cells and saw that the same stress response was turned on. Both cell types were unable to mature and function properly.

Regardless of the cell type, the researchers found that damage to the mitochondria did not cause cell death. This observation brought up the possibility that if they could reverse the damage, the cells would function normally. To do so, they used a drug called ISRIB that blocked the stress response. They found that after four weeks, the β-cells regained their ability to control glucose levels in mice.

Reference: Emily M. Walker et al., Retrograde mitochondrial signaling governs the identity and maturity of metabolic tissues.Science0,eadf2034DOI:10.1126/science.adf2034