Mitochondria play a crucial role in providing energy that powers cells and enables them to operate effectively.
However, defects in mitochondria are linked to the onset of conditions like type 2 diabetes. Individuals suffering from this condition struggle to produce sufficient insulin or to utilize the insulin generated by their pancreas, resulting in elevated blood sugar levels.
Various studies indicate that the insulin-producing pancreatic β-cells in diabetic patients exhibit abnormal mitochondria that are incapable of producing energy. Nevertheless, these investigations failed to clarify the reasons behind this cellular dysfunction.
In research featured in Science, scientists from the University of Michigan used mice to demonstrate that malfunctioning mitochondria activate responses that influence the development and operation of β-cells.
“Our goal was to identify the pathways crucial for sustaining proper mitochondrial function,” explained Emily M. Walker, Ph.D, a research assistant professor in internal medicine and the study’s lead author.
The research team intentionally damaged three key components vital for mitochondrial viability: their DNA, a mechanism for eliminating damaged mitochondria, and a pathway that preserves a healthy pool of mitochondria within the cell.
“In all three instances, the same stress response was activated, resulting in β-cells becoming immature, unable to produce adequate insulin, and effectively ceasing to function as β-cells,” Walker noted.
“Our findings indicate that mitochondria can relay signals to the nucleus and influence the destiny of the cell.”
The researchers also validated their findings with human pancreatic islet cells.
Mitochondrial impairment impacts various cell types
These results prompted the researchers to investigate additional cell types affected by diabetes.
“Diabetes is a systemic condition — you experience weight gain, your liver overproduces sugar, and your muscles are impacted. This is why we aimed to explore other tissues,” said Scott A. Soleimanpour, M.D., the Michigan Diabetes Research Center director and senior author of the paper.
The team replicated their mouse experiments in liver and adipose cells, where they observed the same activation of the stress response. Both types of cells were unable to mature and operate efficiently.
“Although we haven’t explored every conceivable cell type, we believe our findings could be relevant to all tissues affected by diabetes,” Soleimanpour suggested.
Repairing mitochondrial damage could aid in diabetes treatment.
Regardless of the cell type, the research indicated that mitochondrial damage did not lead to cell death.
This observation raised the potential that reversing this damage might restore normal cell function.
To test this, they administered a drug named ISRIB, which inhibited the stress response. After four weeks, they discovered that the β-cells regained their ability to regulate glucose levels in the mice.
“The loss of your β-cells is the most direct pathway to developing type 2 diabetes. Our research now provides an explanation of what may be occurring and how we can intervene to address the underlying issue,” stated Soleimanpour.
The team plans to further investigate the disrupted cellular pathways and hopes to replicate their findings using cell samples from individuals with diabetes.
