Regular physical activity is widely recognized for its benefits to physical health, including improved heart function and weight management. Now, new research suggests that exercise may also directly enhance brain function. A study published in the journal Aging Cell has uncovered a potential mechanism for this benefit, showing that exercise activates specific cellular processes in the brain related to insulin, a hormone essential for blood sugar control. This finding indicates that physical activity might improve how brain cells respond to insulin, which could be a key factor in maintaining cognitive health as we age.
“We believe this work is important because it suggests exercise may work to improve cognition and memory by improving the abilities of insulin to act on the brain,” said Steven Malin, an associate professor in the Department of Kinesiology and Health in the Rutgers School of Arts and Sciences and lead author of the study.
To understand this research, it’s helpful to first understand insulin and neuronal extracellular vesicles. Insulin is a hormone produced by the pancreas. Its primary job is to regulate blood sugar levels, ensuring that our bodies have a steady supply of energy. When we eat, especially foods containing sugars and carbohydrates, our blood sugar levels rise. Insulin helps move this sugar, also known as glucose, from the bloodstream into cells throughout the body, where it can be used for energy or stored for later use.
This process is known as insulin sensitivity, which refers to how well the body responds to insulin. When someone has high insulin sensitivity, their body effectively uses insulin to manage blood sugar. However, in conditions like prediabetes and type 2 diabetes, cells become less responsive to insulin, a condition called insulin resistance. This can lead to high blood sugar levels and various health problems.
While insulin is primarily known for its role in managing blood sugar in the body, it also plays a significant role in the brain. Insulin can cross from the bloodstream into the brain, where it influences brain regions involved in thinking and memory. When brain cells become less responsive to insulin, it can negatively impact cognitive functions. Researchers are increasingly interested in understanding how to maintain or improve insulin sensitivity in the brain to support healthy brain aging.
Neuronal extracellular vesicles are another key element in this study. These are tiny sacs released by brain cells, specifically neurons. For many years, these vesicles were thought to be just cellular waste, but scientists now recognize them as important communicators between cells. Extracellular vesicles act like miniature delivery trucks, carrying various molecules, such as proteins, from one cell to another. In the context of the brain, neuronal extracellular vesicles can transport proteins involved in insulin signaling. This means that by studying these vesicles, researchers can gain insights into what’s happening inside brain cells related to insulin response, without directly examining the brain itself.
For this study, the researchers focused on vesicles produced in the brain that carry proteins involved in insulin sensitivity, including a protein called Akt. By analyzing these vesicles in blood samples, scientists hoped to understand how exercise might affect insulin signaling in the brain.
In this study, researchers wanted to see if exercise could improve brain insulin sensitivity by examining neuronal extracellular vesicles. They recruited 21 volunteers, primarily women, with an average age of 60 who were diagnosed with prediabetes. Prediabetes is a condition where blood sugar levels are higher than normal but not yet high enough to be classified as type 2 diabetes. All participants were considered sedentary, meaning they exercised less than 60 minutes per week, and were non-smokers. They underwent medical examinations to ensure they were healthy enough to participate and were not taking medications that could affect blood sugar.
The study was designed as a short-term exercise trial lasting two weeks. Over this period, participants engaged in 12 supervised exercise sessions, each lasting 60 minutes. The exercise was performed on stationary bicycles at a moderate to high intensity. To ensure consistency, all exercise sessions were individually supervised by researchers. Before and after each training session, and at the beginning and end of the two-week training period, participants consumed a glucose drink. This drink was given to stimulate the body’s insulin response.
To measure the effect of exercise on brain insulin signaling, the researchers collected blood samples from the participants. Blood samples were taken at the start of the study and again after the two-week exercise program. Specifically, blood was drawn before the glucose drink and 60 minutes after consuming it. The researchers then used a specialized technique to isolate neuronal extracellular vesicles from the blood samples. This isolation process targeted vesicles specifically originating from neurons by using a marker protein found on the surface of these vesicles.
Once the vesicles were isolated, the researchers analyzed them for the presence and levels of various proteins involved in insulin signaling. They focused on proteins like Akt, which plays a vital role in how cells respond to insulin. By comparing the levels of these proteins in vesicles collected before and after the exercise program, and before and after the glucose drink, the researchers could assess how exercise affected insulin signaling in brain-derived vesicles.
The analysis of the blood samples revealed that after the two-week exercise program, there was an increase in the number of neuronal extracellular vesicles carrying proteins related to insulin sensitivity. Notably, the amount of the protein Akt within these vesicles increased after each exercise session. This increase was particularly evident after participants consumed the glucose drink, suggesting that exercise enhanced the brain’s insulin response when faced with a rise in blood sugar. In other words, exercise appeared to make brain cells more responsive to insulin signals.
The researchers also observed improvements in the participants’ overall blood sugar control. After the exercise program, participants showed better peripheral insulin sensitivity, meaning their bodies became more effective at using insulin to manage blood sugar. Interestingly, the changes in the Akt protein in the neuronal vesicles were linked to these improvements in blood sugar control and even to a small amount of weight loss experienced by the participants. This suggests a connection between exercise-induced changes in brain insulin signaling and improvements in whole-body metabolic health.
“We showed for the first time that exercise impacts insulin signaling from neuronal extracellular vesicles in relation to clinical improvements in blood sugar,” Malin said. “And we use these neuronal extracellular vesicles as an indicator of brain insulin sensitivity.”
“If insulin is insufficient in the brain, that means not only will brain cells become potentially dysfunctional, but also they may fail to interact with each other properly,” he explained. “It’s like playing the game telephone with a friend. At some point the message gets lost when the brain becomes insulin resistant.”
While this study provides important insights, it is essential to consider its limitations. The study involved a relatively small number of participants, and most were women. Therefore, the findings might not be generalizable to larger, more diverse populations, including men and individuals of different ages or health conditions. Furthermore, the study did not include a control group that did not exercise. While the researchers used the baseline measurements as a comparison, having a non-exercise control group would strengthen the conclusions. Additionally, the study measured changes in proteins within neuronal extracellular vesicles as an indicator of brain insulin sensitivity, but it did not directly measure brain function or cognitive performance.
Future research should build upon these findings by including larger and more diverse groups of participants, incorporating a control group, and examining the effects of different types and durations of exercise. It would also be valuable to investigate how these changes in neuronal extracellular vesicles and brain insulin signaling relate to actual cognitive improvements. Studies that combine blood vesicle analysis with measures of cognitive function and brain imaging would provide a more complete picture of how exercise benefits brain health. Understanding these connections could pave the way for developing more effective exercise strategies to prevent cognitive decline and promote healthy brain aging, especially in individuals at risk for conditions like type 2 diabetes and Alzheimer’s disease.
The study, “Two weeks of exercise alters neuronal extracellular vesicle insulin signaling proteins and pro-BDNF in older adults with prediabetes,” was authored by Steven K. Malin, Daniel J. Battillo, Michal S. Beeri, Maja Mustapic, Francheska Delgado-Peraza, and Dimitrios Kapogiannis.
