Decade-Old Research Team Joins the U’s ‘Academies for Excellence’

Pictured: Some of the team leading the research on the impact of diabetes and obesity on the brain.

“It’s like building a wall. Everyone adds a brick, I add my own brick on top of that and together with this team, we use it to address a very serious biomedical problem,” said Gulin Oz, PhD, who is a professor in the Department of Radiology at the University of Minnesota Medical School.

That biomedical problem—how diabetes and obesity impact the brain—has been at the center of Dr. Oz and a U of M team’s collaborative research over the last decade. This team, which includes Dr. Oz, Amir Moheet, MBBS, an associate professor in the Department of Medicine, and Elizabeth Seaquist, MD, a professor in the Department of Medicine, grew their expertise throughout the years to include Silvia Mangia, PhD, a professor in the Department of Radiology, Lynn Eberly, PhD, a professor in the School of Public Health, and Lisa Coles, PhD, an associate director in the College of Pharmacy.

“Together, we bring four sets of expertise—the clinical, the magnetic resonance imaging, the biostatistics and the pharmacology,” Dr. Oz said.

Since 2003, this interdisciplinary team has published more than 30 peer-reviewed publications on their research, participated in the performance of three clinical trials and received more than $7 million in research funding, including three R01 grants from the National Institutes of Health. This month, the team received one more award—induction into the University’s Academy for Excellence in Team Science.

“We tend to recognize individuals a lot, but in this case, I really appreciate that our institution is recognizing team science more and more. It’s never the individuals—it’s always a team,” Dr. Oz said.

“With the kind of research I’m doing, I cannot do any significant part of it by myself,” Dr. Moheet added. “This award stresses how complex science has become and how important it is for team science. Being honored motivates and energizes you.”

First in the World

While the team could celebrate many successes from the last decade, they agree that their biggest accomplishment is being first in the world to study brain glycogen in humans and its connections to diabetes. Glycogen is a storage form of glucose, or sugar, most often found in the liver. Dr. Seaquist says, though, it also exists in the brain and has a direct impact on hypoglycemia, or low blood sugar.

“We’ve been very interested in understanding if this storage form of glucose is useful during periods of low blood sugar to help keep brain metabolism going,” Dr. Seaquist said. “While I think our results have not really answered that question yet to date, what is amazing is the methodology that we have developed to study this. No one else in the world is able to do this kind of work with the success that we’ve had, and it’s really helped other people across neuroscience and metabolism to think about how storage forms of glucose may be used for different processes.”

The team’s pioneering research methods study the effects of repeated occurrences of hypoglycemia on the brain. The phenomenon, which is especially common in patients with Type I diabetes, begins when patients inadvertently overdose on insulin. Their blood sugar drops, and if this happens repeatedly, patients develop an impaired awareness of when they are hypoglycemic.

“You don’t get sweaty or shakey, and you don’t know to eat to increase your blood sugar back to normal. There are a lot of different ideas on why this happens, and glycogen is one idea,” Dr. Oz said.

That idea is being studied by Dr. Oz and the team, which theorizes that after one episode of hypoglycemia, the brain makes extra glucose storage in the form of glycogen, so that during the next hypoglycemic episodes, the brain can tap into that resource for help. Patients with diabetes who take insulin for treatment, including all Type 1 and many Type 2 patients, experience episodes of hypoglycemia on a daily or weekly basis.

“The danger of hypoglycemia unawareness is you don’t know that your blood sugar is low and you don’t take the measures to correct it, so the first symptom may be fainting. Somebody may be driving, not know they are hypoglycemic and may get into an accident. This is a very dangerous condition that we don’t fully understand. But, we’re learning more,” Dr. Oz said. “Before our studies, nobody else could detect glycogen signal from the human brain and monitor its metabolism. Our studies have shown evidence of the brain making more than normal levels of glycogen after exposure to low blood sugar, and we are the only group who has shown evidence along those lines in the human brain.”

More to Discover

While the team will continue its pursuit to further understand the impacts of diabetes and hypoglycemia, they also found new, but related, paths of research to study—how does the brain change following weight loss from bariatric surgery?

“Obesity, just like diabetes, also affects brain structure and function, and obesity is a risk factor for developing dementia,” Dr. Moheet said. “We are using the techniques we’ve developed in our earlier studies to now understand how obesity affects brain structure. We have an ongoing study in patients undergoing bariatric (weight loss) surgery, and the results so far show that they improve their cognitive function after losing weight through this surgery.”

By comparing brain imaging data acquired in collaboration with Dr. Oz and Dr. Mangia on patients before and after surgery, Dr. Moheet says this new direction of research may lead to additional discoveries in obesity-related cognitive dysfunction.

“It’s pretty exciting. Using these state-of-the-art methods, we can examine the human brain and measure neurotransmitters and neurochemicals to see what changes in the brain are happening after weight loss,” Dr. Moheet said. “Hopefully, that will help us better understand and build biomarkers that identify people who are at greater risk of developing cognitive dysfunction in the future.”

To see a full list of this year’s inductees into the Academies for Excellence, including additional Medical School faculty, please visit this website.

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