A recently published study led by John Kirwan, the new executive director of the University of Oklahoma Health Harold Hamm Diabetes Center, identified a protein that may contribute to insulin resistance. Kirwan said the protein, known as Miro1, could be a target for future treatments to help the body regulate blood sugar.
Kirwan joined the center in September after serving eight years as executive director at the Pennington Biomedical Research Center at Louisiana State University. Before that, he spent about 20 years at the Cleveland Clinic, where he founded and directed the Metabolic Translational Research Center.
The translational scientist traveled 632 miles from the life he built in Louisiana to Oklahoma because he saw an opportunity to create impact in a state where, in 2024, 13.2% of adults had been diagnosed with diabetes.
The chronic disease occurs when the pancreas does not produce enough insulin or the body cannot effectively use the insulin it makes. Insulin regulates blood sugar. If untreated, elevated blood sugar can damage nerves, blood vessels, tissues and organs.
Kirwan said he has been working to understand why insulin doesn't always work for more than 30 years. This new study, available in the journal “Nature Communications,” is part of that story, he said.
Miro1 is found on the outer membrane of mitochondria, which are structures inside cells essential to generating energy that helps cells function.
Researchers analyzed Miro1 in cells, preclinical models and people living with Type 2 diabetes, allowing them to explore its effects on muscle function from the cellular level to its potential relevance in diabetes.
The team – which examined patients who had a healthy weight, were obese without Type 2 diabetes or were obese with Type 2 diabetes – found that Miro1 accumulated in the skeletal muscles of patients who had the chronic condition. The study shows that this interferes with the muscles’ response to insulin.
Kirwan said the researchers found that removing Miro1 in preclinical models restored the muscle’s insulin response, creating evidence that the protein may directly inhibit this process.
In a separate, 12-week randomized controlled trial involving people with obesity and Type 2 diabetes, researchers compared outcomes among participants who underwent aerobic training and those who received standard medical care. People in the exercise group saw reductions in muscle Miro1 levels and improvements in insulin sensitivity and the muscles’ capacity to produce energy.
Kirwan said this study is a great first step. But more research is needed to determine whether targeting Miro1 could lead to new treatments.
“Can you produce a drug that can control the Miro1 levels? And, if you do, what is the effect on the rest of the body? So we don't know that from these experiments yet,” Kirwan said. “The next steps will be to target that protein, figure out how it's working. And then see, ‘Can we produce an alternative?’ Because not everybody can exercise, and not everybody will exercise.”
A new vision for diabetes research in Oklahoma
Kirwan said this is one of the many topics he hopes to focus on in his new role in Oklahoma. Billionaire oil executive Harold Hamm recently committed $150 million to OU to support health education and research. One-third of that money is going to the diabetes center named after him.
Approximately $30 million will support Kirwan’s priorities for the OU Health Harold Hamm Diabetes Center and $20 million will support capital improvements and research infrastructure, according to a press release.
Kirwan said the center is creating a blueprint for the investment that will be revealed in January. The center will consult with its advisory board, business leaders, lawmakers and tribal nations on what this will include.
Kirwan said it will focus on four things: cures for Type 1 diabetes, remission for Type 2 diabetes, complications and community. OU has committed to reducing diabetes complications and related deaths in Oklahoma by 30% over five years.
“We have an opportunity here to work with the community, addressing a very pressing problem for them,” Kirwan said.
The center is also currently recruiting 40 diabetes investigators as part of Project 200. The initiative is working to attract approximately 200 researchers to OU to strengthen the state’s health, economy and future.
“We want the best brain power that we can find – to focus them on fixing this problem,” Kirwan said.
Kirwan said the center will work “hand in glove” with state lawmakers to enhance and improve the health of Oklahoma’s population. He referenced a public service initiative developed during his time in Louisiana called Greaux Healthy. The program, created in partnership with Pennington Biomedical Research Center and the State of Louisiana, focuses on preventing and treating childhood obesity in the state.
“That program was initiated through our work with the legislature and their investment in the children of Louisiana and the kids of the state and the future of the state,” Kirwan said. “And we would hope to carry the same message to Oklahoma and develop similar programs.”
Kirwan added that he has experience working in a state eligible for the Institutional Development Award. This congressionally mandated program builds research capacity in states with historically low levels of National Institutes of Health funding.
The center will collaborate with Oklahoma’s congressional delegation to facilitate the resources needed to address diabetes in the state, he said.
“I think bringing the right message, meeting with the right people, bringing the right people together – you can move the needle here,” Kirwan said.
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