- Researchers found elevated levels of the mitochondrial protein Miro1 in the skeletal muscles of people with type 2 diabetes, potentially impairing the muscles’ response to insulin.
- In preclinical models, eliminating the protein improved muscle insulin sensitivity, suggesting that Miro1 could be a potential target for future diabetes treatments.
- In a randomized controlled trial involving people with obesity and type 2 diabetes, aerobic exercise reduced muscle Miro1 levels and improved insulin sensitivity and the muscles’ ability to produce energy.
- The findings provide new insights into the mechanisms underlying insulin resistance, however, further studies are necessary to determine whether Miro1 could provide a suitable target for diabetes treatment.
Insulin resistance occurs when the body’s cells do not respond effectively to insulin, while insulin sensitivity refers to how effectively cells respond to the hormone.
In type 2 diabetes, insulin resistance can cause the pancreas to produce more insulin to compensate. Over time, it may become unable to produce enough insulin to regulate blood glucose levels, which may contribute to the development and progression of type 2 diabetes.
Now, research suggests that a protein, known as mitochondrial Rho GTPase 1 (Miro1), is found at elevated levels in the skeletal muscles of people with type 2 diabetes and may directly impair insulin responsiveness.
The study, published in
The findings could help researchers better understand the biological mechanisms underlying insulin resistance and identify potential targets for future treatments. However, further research is necessary to establish whether directly targeting Miro1 could lead to effective treatments for people with type 2 diabetes.
Miro1 may play active role in insulin resistance
Miro1 is a protein found on the outer membrane of mitochondria, which are the structures within cells that produce energy. Research suggests that the protein may play a role in insulin resistance by influencing how skeletal muscle cells respond to insulin.
“This study suggests that when Miro1 accumulates excessively in skeletal muscle, it may interfere with the muscle’s ability to respond effectively to insulin,” Opel Baker, MBChB, general practitioner at the Mayfield Clinic, who was not involved in the study, explained to Medical News Today.
“Normally, insulin activates a signaling pathway involving a protein called AKT, which helps move glucose transporter proteins, known as GLUT4, to the muscle cell surface so glucose can enter. In people with type 2 diabetes, this signaling process appears to be disrupted, allowing Miro1 to accumulate and potentially impair further glucose uptake.”
— Opel Baker, MBChB
To understand its role in diabetes, researchers examined the protein in cells, preclinical models, and people living with type 2 diabetes, enabling them to investigate Miro1’s effects on muscle function from the cellular level to its potential relevance in diabetes.
Notably, the team found that Miro1 accumulated in the skeletal muscles of people with type 2 diabetes and the protein could contribute directly to impaired insulin responsiveness. They also found that removing Miro1 restored the muscle’s response to insulin in preclinical models, suggesting that the protein may play an active role in insulin resistance rather than simply being associated with it.
“The researchers found that Miro1 accumulation was associated with defective insulin signaling, specifically reduced movement of activated AKT to the mitochondria and less interaction between AKT and Miro1,” Baker told MNT.
Insulin regulates Miro1 levels
“This suggests that insulin normally helps regulate Miro1 levels, but this process becomes impaired in type 2 diabetes. Excess Miro1 may contribute to disrupted mitochondrial function, reduced energy-producing capacity and impaired glucose uptake by muscle cells. However, the precise mechanisms still require further investigation, and Miro1 accumulation may be both a consequence of insulin resistance and a contributor to its progression.”
— Opel Baker, MBChB
Exercise may reduce Miro1 levels in people with type 2 diabetes
The researchers also investigated whether exercise affected Miro1 levels in skeletal muscle using data from a randomized controlled trial involving people with obesity and type 2 diabetes. Participants in the trial received either an aerobic exercise intervention or standard medical care.
Those in the exercise group experienced reductions in muscle Miro1 levels, alongside improvements in insulin sensitivity and muscle energy production, suggesting that changes in Miro1 may be one of the biological mechanisms underlying the metabolic benefits of exercise.
However, the results do not establish that reducing Miro1 is solely responsible for the improvements in insulin sensitivity. Exercise affects numerous processes involved in glucose regulation, muscle function, and energy metabolism.
However, the study provides a potential new explanation for some of the beneficial effects of physical activity in people with type 2 diabetes.
Could Miro1 become a target for future diabetes treatments?
The findings suggest that treatments targeting Miro1 activity or its accumulation could improve insulin sensitivity. Investigating Miro1 across cellular experiments, preclinical models, and human studies identifies Miro1 as a potential therapeutic target and provides further insight into the relationships among muscle function, insulin resistance, and exercise.
The findings are particularly relevant because
However, the results do not indicate that Miro1-targeting treatment would necessarily be safe and effective in humans.
Further studies will need to determine how Miro1 contributes to insulin resistance, whether its effects can be targeted therapeutically, and what potential benefits or risks this approach might have.
What do the findings mean for people with type 2 diabetes?
The research offers a promising direction for future investigations into type 2 diabetes, but it does not change current treatment recommendations. Aerobic exercise remains an important part of diabetes management for many people, alongside appropriate medical care, dietary measures, and medication when necessary.
The observed reduction in Miro1 levels following exercise may help researchers understand another way physical activity improves insulin sensitivity. However, the study does not establish that measuring or lowering Miro1 directly would improve clinical outcomes.
“The findings offer a potential explanation for why exercise improves blood glucose regulation beyond simply increasing the amount of glucose muscles use during physical activity,” Baker noted. “In a 12-week exercise intervention, participants with obesity and type 2 diabetes showed reduced muscle Miro1 accumulation alongside improvements in insulin sensitivity and mitochondrial function.”
“Exercise may therefore help restore the way muscle cells respond to insulin by improving mitochondrial health and the signaling processes that regulate glucose uptake,” he explained. “This provides further insight into the biological mechanisms behind exercise’s established metabolic benefits, although the study does not prove that reducing Miro1 is solely responsible for those improvements.”
The findings also highlight the importance of studying diabetes at several levels, from the molecular processes occurring inside cells to the effects of interventions in people. For now, Miro1 represents a potential therapeutic target rather than an established treatment.
“The key message is that exercise may help improve the underlying metabolic function of skeletal muscle, making it more responsive to insulin, rather than simply burning calories or using glucose temporarily. These findings strengthen our understanding of how regular physical activity may support better glucose control and mitochondrial health.”
— Opel Baker, MBChB
“However, this is not a reason to change current treatment recommendations,” Baker said.
“People living with type 2 diabetes should continue to follow personalized advice on physical activity, medication and nutrition from their healthcare team. The study also does not establish a new exercise prescription or show that Miro1 testing or targeted treatment is currently appropriate in clinical practice,” he concluded.
