Mitochondrial damage is common in metabolic diseases like Diabetes, affecting insulin production and function in patients. Diabetics’ insulin-producing β-cells have abnormal mitochondria, impairing energy generation. Previous studies couldn’t explain why this happened.
A study by the University of Michigan found that dysfunctional mitochondria affect β-cell maturation and function in mice. Researchers damaged three key mitochondrial components: DNA, a pathway to remove damaged mitochondria, and one maintaining healthy mitochondria.
This activated a stress response, causing β-cells to become immature and stop producing enough insulin.
Emily M. Walker, Ph.D., a research assistant professor of internal medicine and the study’s first author, said, “Our results demonstrate that the mitochondria can send signals to the nucleus and change the fate of the cell.”
The findings were confirmed in human pancreatic islet cells, leading researchers to investigate other cells affected by Diabetes. They repeated experiments in liver and fat-storing cells in mice, observing the same stress response and impaired function.
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Scott A. Soleimanpour, M.D., director of the Michigan Diabetes Research Center and senior author of the study, said, “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.”
They believe these results could apply to other tissues affected by Diabetes.
Regardless of the cell type, researchers found that mitochondrial damage did not cause cell death. This suggested that reversing the damage could restore cell function.
Using ISRIB, a drug that blocks the stress response, they found that β-cells regained their ability to control glucose levels in mice after four weeks.
“Losing your β-cells is the most direct path to getting type 2 diabetes. Our study explains what might be happening and how we can intervene to fix the root cause,” Soleimanpour said.
The team is further studying disrupted cellular pathways and aims to replicate their results in diabetic patient cell samples.
Journal Reference:
- Emily Walker, Gemma Pearson, et al. Retrograde mitochondrial signaling governs the identity and maturity of metabolic tissues. Science. DOI: 10.1126/science.adf2034
Source: Tech Explorist
