Researchers have identified a protein that may play an important role in type 2 diabetes by interfering with the body’s ability to respond to insulin.
The protein, known as Miro1, was found at higher levels in the skeletal muscles of people with the disease, suggesting it could be a potential target for new treatments to improve blood sugar control.
Miro1, or mitochondrial Rho GTPase 1, is located on the outer membrane of mitochondria, which are the structures inside cells responsible for energy production. The study, published in Nature Communications, indicates that excessive buildup of this protein may impair how muscles respond to insulin.
Miro1 accumulation impairs insulin signaling and muscle response
To investigate the link between the protein and diabetes, the research team examined Miro1 in laboratory cells, preclinical models, and human patients. The results showed that Miro1 accumulation was associated with defective insulin signaling. Specifically, researchers observed reduced movement of activated AKT to the mitochondria and less interaction between AKT and Miro1.
In preclinical experiments, scientists discovered that removing the protein restored the muscles’ response to insulin. “By tracing Miro1 from cells to preclinical models to patients, we show that Miro1 accumulation impairs the muscle’s response to insulin, that removing it causally restores that response in our models, and that exercise reverses its buildup in people,” said Dr. John P. Kirwan, the study’s senior author.
Opel Baker, a general practitioner not involved in the study, explained to Medical News Today that insulin normally helps regulate Miro1 levels, but this process appears disrupted in type 2 diabetes. Baker noted that in people with the disease, the signaling process that helps move glucose transporter proteins to the cell surface appears disrupted, which may allow Miro1 to accumulate and further impair glucose uptake.
The link between exercise and protein levels
The researchers also conducted a randomized controlled trial to see if physical activity influences Miro1. The trial involved participants living with obesity and type 2 diabetes and compared standard medical care against aerobic exercise. Those assigned to the exercise group experienced a decline in Miro1 levels in their muscles, which occurred alongside improved insulin sensitivity and an increased capacity for the muscles to produce energy.
These findings suggest that reducing Miro1 may be one of the mechanisms by which exercise helps the body respond to insulin. Dr. Kirwan stated that the research “opens a path toward treatments that could one day complement” physical activity.
While the study provides new insights into the biological processes behind insulin resistance, further research is necessary to determine if directly targeting Miro1 will result in effective medical treatments for people with type 2 diabetes.
