Mitochondria are well known as the powerhouses of the cell. These crucial, energy generating organelles even have their own little genomes, and make their own proteins. Mutations in mitochondrial DNA (mtDNA) can cause some serious diseases, and dysfunctional mitochondria have been associated with a wide variety of health disorders. Researchers have also found links between mitochondrial defects and diabetes.
There are special cells in the pancreas known as beta cells, which is where insulin is generated. When these cells are lost due to an autoimmune attack, type 1 diabetes arises. Some studies have determined that there are abnormal mitochondria in the beta cells of some diabetes patients.
A new study has used a mouse model to show that mitochondrial dysfunction can disrupt the maturation and function of beta cells. This work was also confirmed in human beta cells. These findings, which have been reported in Science, may have major implications for the study of diabetes.
"We wanted to determine which pathways are important for maintaining proper mitochondrial function," said first study author Emily M. Walker, PhD, a research assistant professor at the University of Michigan.
In this work, the researchers disrupted mitochondria in several ways. In one, they damaged mitochondrial DNA. In other cases they altered a pathway that eliminates damaged mitochondria from cells. They also interfered with another biochemical pathway that maintains a cell's healthy mitochondria. In every case, a stress response was triggered that interfered with beta cell maturation, Walker explained.
These immature beta cells stopped making sufficient insulin.
"Our results demonstrate that the mitochondria can send signals to the nucleus and change the fate of the cell," noted Walker.
"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 senior study author Scott A. Soleimanpour, MD, director of the Michigan Diabetes Research Center.
When the researchers aimed to disrupt mitochondria in liver or fat cells, the same stress response pathway was activated, again and again. These cell types all ceased to mature, and stopped functioning correctly.
The study authors suggested that while every cell type has not been tested, they may all react in similar ways.
This mitochondrial damage did not kill the cells, however, suggesting that it may be possible to reverse this damage.
When the stress response pathway was blocked with a drug, beta cells were shown to eventually begin to mature again, and started regulating blood sugar properly in a mouse model.
"Losing your beta 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 researchers want to confirm these findings in diabetic patients next.
Sources: University of Michigan, Science