Posted on 02/18/2025 6:45:43 AM PST by Red Badger
Mitochondrial dysfunction in β-cells can cause their immaturity and impaired insulin production, contributing to diabetes. Researchers identified a stress response triggered by damaged mitochondria that prevents these cells from functioning properly, but blocking the response with a drug restored their ability to control glucose in mice.
Mitochondrial stress disrupts insulin production in diabetes, but reversing the damage may restore β-cell function.
Mitochondria are essential for generating the energy that fuels cells and enables them to function.
However, mitochondrial defects are linked to the development of diseases such as type 2 diabetes. Patients with this disorder either cannot produce enough insulin or cannot effectively use the insulin their pancreas produces to maintain normal blood sugar levels.
Several studies have shown that the insulin-producing pancreatic β-cells of diabetic patients have abnormal mitochondria and fail to generate sufficient energy. Yet, these studies have not explained why the cells behave this way.
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 β-cells.
“We wanted to determine which pathways are important for maintaining proper mitochondrial function,” said Emily M. Walker, Ph.D, a research assistant professor of internal medicine and first author of the study.
To do so, the team 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,” Walker said.
“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.
Mitochondrial dysfunction affects several types of cells Their results prompted the team to expand their search into other cells that are affected during diabetes.
“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 Scott A. Soleimanpour, M.D., director of the Michigan Diabetes Research Center and senior author of the study.
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.
“Although we haven’t tested all possible cell types, we believe that our results could be applicable to all the different tissues that are affected by diabetes,” Soleimanpour said.
Reversing mitochondrial damage could help cure diabetes 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.
“Losing your β-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 team is working on further dissecting the cellular pathways that are disrupted and hope that they will be able to replicate their results in cell samples from diabetic patients.
Reference:
“Retrograde mitochondrial signaling governs the identity and maturity of metabolic tissues”
by Emily M. Walker, Gemma L. Pearson, Nathan Lawlor, Ava M. Stendahl, Anne Lietzke, Vaibhav Sidarala, Jie Zhu, Tracy Stromer, Emma C. Reck, Jin Li, Elena Levi-D’Ancona, Mabelle B. Pasmooij, Dre L. Hubers, Aaron Renberg, Kawthar Mohamed, Vishal S. Parekh, Irina X. Zhang, Benjamin Thompson, Deqiang Zhang, Sarah A. Ware, Leena Haataja, Nathan Qi, Stephen C. J. Parker, Peter Arvan, Lei Yin, Brett A. Kaufman, Leslie S. Satin, Lori Sussel, Michael L. Stitzel and Scott A. Soleimanpour, 6 February 2025, Science.
DOI: 10.1126/science.adf2034
Funding: Breakthrough T1D, NIH/National Institutes of Health, Department of Veterans’ Affairs, American Diabetes Association
Or... I know this is crazy, we could take the poison out of our food.
Interesting thesis. I’m wondering what they regard as the causes of this “mitochondrial damage.”
My guess:
Climate Change.....................
Nah......................
“One weird trick”
Please make this stop.
Just a few days ago, they FINALLY started to admit that diet can control diabetes.
So it sounds like RFK is already poking around and now people that have been ordered to keep quiet about dealing with diabetes are trying to get out in front, before the HAMMER drops on them.
Humans can become “sugar burners”, even at the mitochondrial level. Cells show a clear preference for burning glucose. The pathways for for the uptake and reregulation for burning fatty acids become atrophied with disuse.
This is probably why intermittent fasting, and calorie restriction, low-carb works so effectively. Critics say “starving yourself” but it isn’t starving, it forces the body to relearn how to do something it is intended to do - burn fat for energy. There is only one organ in the human body that requires glucose, the brain, and our bodies can synthesize all that is required from fat. Imagine that.
Well, I did. I've been doing 16hrs+ of intermittent fasting now for nearly four years with little improvement in fasting glucose numbers hanging just above 100.
Are you trying to lose fat? I lost 80+ pounds intermittent fasting. It was the calorie restriction of course that does all the work. Sometimes as little as 600 to 800 calories. Most people don’t want to do that, not for very long anyway.
At 6-0 X 175#, I could lose a few, but not really. When I started the fasting, I lost 40# to the point that I had virtually no fat at all, but gained back ten very quickly. 165# was fine. It stayed steady for three years until I suddenly picked up another ten since last Thanksgiving. So I'm paying attention.
The work I do is either very physical or completely sedentary but intellectually demanding.
Likely. Free speech is a possibility.
A new, non generic, Big Pharma offering! - Creating permanent lifetime customers.
Something tells me that this involves ‘a pill’ or the like. /s
...rather than taking some personal responsibility...
YOUR QUESTION IS SPOT ON: EXCESS MITOCHONDRIAL IRON CAUSES THE ACCUMULATION OF EXCESS UNMATCHED ELECTRONS (REACTIVE OXYGEN SPECIES) IN THE ELECTRON TRANSPORT CHAIN IN THE PRODUCTION OF ENERGY (ATP). THIS PHENOMENA HAS BEEN WELL PUBLISHED FOE 20 YEARS. I REPRESENT MULTIPLE GRANTED PATENTS ON THIS SUBJECT MATTER.
Would this “excess mitochondrial iron” at all correspond to ferritin and hemoglobin test results?
bkmk
A few more flaming trucks of grant money, if you please.
Nah. High fructose corn syrup is the bomb. Literally.
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