A study led by scientists at Rutgers University-New Brunswick has shown that specialized cells involved in how the body responds to insulin are activated in the brain after exercise, suggesting that physical activity can directly improve brain function .
A study published in Aging cella journal focusing on the biology of aging indicates that therapies that target this insulin action could be developed to compensate for or even prevent the progression of dementia.
We believe this work is important because it suggests that exercise may work to improve cognition and memory by improving the ability of insulin to act on the brain.”
Steven Malin, associate professor in the Department of Kinesiology and Health at Rutgers School of Arts and Sciences and lead author of the study
Conducted in collaboration with the National Institute on Aging of the National Institutes of Health, the researchers focused on the role of neuronal extracellular vesicles, specialized cells released by the brain.
Extracellular vesicles, once dismissed by researchers as “cell matter,” have grown exponentially in recognition over the past fifteen years as key players in the microscopic world of the human body, facilitating the transport of key molecules such as proteins between cells. For this study, the scientists focused on vesicles produced in the brain that carry several proteins involved in insulin sensitivity – one of which is called Akt.
Insulin sensitivity is a measure of how well the body responds to insulin, a hormone that regulates blood sugar levels. People with high insulin sensitivity can use blood glucose more effectively in the body, for example in the muscles, which lowers blood sugar levels. People with diabetes, whose main symptom is low insulin sensitivity or insulin resistance, have brain cells that are less responsive to insulin. This can have negative consequences for cognition.
Researchers were able to study the vesicles by isolating them in the blood of participants in an experimental study. The trial, which lasted two weeks, involved a group of 21 volunteers with an average age of 60 and prediabetes. Over the course of the study, they took part in twelve individual, 60-minute supervised exercise sessions of moderate to high intensity. The participants drank a glucose drink before and after training. Researchers then collected blood samples from the participants before and during the drinks at the beginning and end of the exercise training.
The blood samples showed that the number of neuronal vesicles containing proteins involved in insulin sensitivity increased after each training session, with Akt being the most noticeable.
“We have shown for the first time that exercise influences insulin signaling from neuronal extracellular vesicles in relation to clinical improvements in blood glucose control,” Malin said. “And we use these neuronal extracellular vesicles as an indicator of the brain’s insulin sensitivity.”
Exercise may therefore be able to improve the brain’s ability to respond to insulin for neuronal function, he said.
Insulin is a hormone that is increasingly recognized to regulate cognition, the mental process of acquiring knowledge through thoughts, experiences, and senses. Prediabetes is a serious health condition that occurs when blood sugar levels are higher than normal, but not high enough to be diagnosed as type 2 diabetes. Those with prediabetes are at risk of not having enough insulin in their body, especially in the brain, which affects the chances of developing dementia diseases such as Alzheimer’s disease, Malin said.
Insulin also plays a crucial role in memory formation, recall, processing speed and the functioning of synapses, structures that allow brain cells to communicate with each other.
“If insulin is insufficient in the brain, not only does it mean that brain cells may become dysfunctional, but they may also not be able to communicate with each other properly,” Malin said. “It’s like playing on the gaming phone with a friend. At some point the message is lost as the brain becomes insulin resistant.”
Exercise has long been believed to improve cognition, but the mechanisms involved are unclear. Previous studies have found that high blood sugar contributes to a decrease in the brain’s ability to remember information and learn new information.
Malin said insulin, which is produced by the pancreas and travels to the brain to perform its functions, plays a central role in promoting blood flow in the brain and neuronal functioning for cognition.
“Our work suggests that therapies that target the action of brain insulin may prevent dementia,” Malin said.
In a new study, Malin and colleagues investigate whether a single exercise can improve the ability of intranasal insulin to support cognitive health in older adults with obesity by measuring brain blood flow and neuronal extracellular vesicles. Their future plans are to conduct a long-term exercise training study assessing improvements in brain insulin sensitivity in relation to cognition in older adults.
Other Rutgers scientists who participated in the study included Michal Beeri, director of the Herbert and Jacqueline Krieger Klein Alzheimer’s Research Center at Rutgers Robert Wood Johnson Medical School; and Daniel Battillo, a doctoral candidate in the kinesiology and applied physiology graduate program. Scientists from the National Institute of Aging at the National Institute of Health involved in the study included Dimitrios Kapogiannis, Maja Mustapic and Francheska Delgado-Peraza.
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Magazine reference:
Malin, SK, et al. (2024). Two weeks of exercise alter neuronal extracellular vesicle insulin signaling proteins and pro-BDNF in older adults with prediabetes. Aging cell. doi.org/10.1111/acel.14369.