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Researchers have identified a protein that may contribute to insulin resistance in people with Type 2 diabetes, opening a potential new avenue for treatment and offering fresh insight into how exercise helps control blood sugar.
The protein, known as Miro1, was found at elevated levels in the skeletal muscles of people with Type 2 diabetes. Experiments showed that removing the protein restored muscle responsiveness to insulin, while exercise reduced its levels in people with the disease.
The findings, published in Nature Communications, could help scientists better understand the biological mechanisms behind insulin resistance, a key feature of Type 2 diabetes.
Miro1 (Mitochondrial Rho GTPase 1) is located on the outer membrane of mitochondria, the structures inside cells responsible for energy production.
Researchers examined the protein in laboratory cells, preclinical models and people with Type 2 diabetes. They found that excessive Miro1 accumulation impaired the ability of skeletal muscles to respond to insulin.
Removing the protein restored insulin responsiveness in preclinical models, suggesting that Miro1 plays a direct role in the development of insulin resistance.
The team also investigated the effects of exercise through a randomised controlled trial involving people with obesity and Type 2 diabetes. Participants who undertook aerobic exercise showed reduced Miro1 levels in their muscles, alongside improvements in insulin sensitivity and energy production.
The findings suggest that reducing Miro1 levels may be one mechanism through which physical activity improves the body’s response to insulin.
Dr John P Kirwan, the study’s senior author, said insulin resistance in muscles was central to Type 2 diabetes, but its underlying molecular causes had remained unclear.
By examining Miro1 from laboratory experiments to preclinical models and human studies, researchers identified the protein as a potential therapeutic target, he said.
Kirwan recently became executive director of the OU Health Harold Hamm Diabetes Center at the University of Oklahoma. He conducted the research while working at Louisiana State University’s Pennington Biomedical Research Center.
Study first author Elizabeth Heintz is a doctoral candidate who worked at Pennington Biomedical, while co-corresponding author Christopher Axelrod has also joined the Harold Hamm Diabetes Center.
Dr Jennifer Rood, interim senior vice chancellor and executive director of Pennington Biomedical, said the research demonstrated the importance of linking basic scientific discoveries with clinical studies.
She said the findings connected fundamental insights into muscle function with a better understanding of insulin resistance and the benefits of exercise in people with Type 2 diabetes.
However, researchers cautioned that further studies are needed to determine whether directly targeting Miro1 can lead to safe and effective treatments.
While removing the protein restored insulin responsiveness in preclinical models, the human study demonstrated a reduction in Miro1 through exercise rather than a drug-based intervention.
The discovery could eventually support the development of therapies that complement exercise and existing treatments for Type 2 diabetes.
