Curious about how exercise protects brain health? Read on about how short-term training improves insulin signaling and lower Alzheimer’s risk!
Engaging in regular physical activity is widely associated with numerous benefits for overall well-being, including enhanced cardiovascular function and effective weight regulation.
Emerging research now highlights an additional advantage, revealing a potential link between exercise and improved brain function. A study published in the journal Aging Cell has identified a possible mechanism behind this effect, demonstrating that physical activity activates specific cellular processes in the brain associated with insulin, a hormone crucial for blood sugar regulation. These findings suggest that movement-based activities may contribute to better insulin responsiveness within brain cells, potentially supporting cognitive health throughout aging.
“This work is considered important because it suggests that cognition and memory may be enhanced through improved insulin function in the brain,” stated Steven Malin, an associate professor in the Department of Kinesiology and Health at Rutgers School of Arts and Sciences and lead author of the study.
Steven Malin
A clearer understanding of this research requires familiarity with insulin and neuronal extracellular vesicles.
Insulin, produced by the pancreas, plays a fundamental role in regulating blood sugar levels, ensuring a consistent energy supply. Following the consumption of foods containing sugars and carbohydrates, blood sugar levels rise, prompting insulin to facilitate glucose movement from the bloodstream into body cells for immediate energy use or future storage.
This process, known as insulin sensitivity, reflects how efficiently the body responds to insulin. High insulin sensitivity allows for effective blood sugar management, whereas conditions such as prediabetes and type 2 diabetes are marked by diminished cellular responsiveness to insulin, a state referred to as insulin resistance. This impairment can result in elevated blood sugar levels and a range of associated health concerns.
While insulin is primarily recognized for its essential role in blood sugar regulation, its influence extends to brain function. This hormone crosses from the bloodstream into the brain, where it interacts with regions responsible for cognition and memory. A decline in insulin responsiveness within brain cells has been associated with negative effects on cognitive function, prompting growing scientific interest in strategies that support insulin sensitivity in the brain to promote healthy aging.
Neuronal extracellular vesicles represent another crucial aspect of this research. These microscopic sacs, released by neurons, were once thought to be mere cellular waste but are now understood as vital components of cell-to-cell communication. Acting as molecular transporters, these vesicles carry various proteins, including those involved in insulin signaling, between cells. Within the brain, neuronal extracellular vesicles offer insight into insulin-related processes, enabling researchers to assess brain cell function through blood samples rather than direct brain examination.
This study focused on vesicles containing proteins linked to insulin sensitivity, such as Akt, a key protein involved in insulin signaling. By analyzing these vesicles in blood samples, researchers aimed to explore how physical activity might influence insulin function in the brain.
The research
To investigate this connection, a group of 21 participants, primarily women with an average age of 60, was selected. All participants had been diagnosed with prediabetes, a condition characterized by elevated blood sugar levels that have not yet reached the threshold for type 2 diabetes. Each individual led a sedentary lifestyle, engaging in less than 60 minutes of exercise per week, and none were smokers. Prior to participation, medical evaluations were conducted to confirm eligibility and ensure that no medications affecting blood sugar levels would interfere with the study.
The study was structured as a short-term exercise trial spanning two weeks. During this period, a total of 12 supervised exercise sessions were completed, each lasting 60 minutes. Stationary cycling at moderate to high intensity served as the chosen form of physical activity. To maintain consistency, direct supervision was provided throughout each session. At designated time points—before and after each exercise session, as well as at the beginning and conclusion of the two-week program—a glucose drink was administered to stimulate the body’s insulin response.
To evaluate the effects of exercise on brain insulin signaling, blood samples were collected at multiple intervals. These samples were obtained both at the start of the study and following the completion of the two-week program. Blood was drawn before glucose consumption and again 60 minutes after intake. A specialized technique was then utilized to isolate neuronal extracellular vesicles from the collected samples. This isolation process specifically targeted vesicles originating from neurons, identified by a distinct marker protein present on their surface.
Following isolation, an analysis was conducted to measure the presence and levels of proteins involved in insulin signaling. Particular attention was given to proteins such as Akt, a key component in cellular insulin responsiveness. Comparisons were made between protein levels in vesicles obtained before and after the exercise program, as well as before and after glucose intake, to determine the influence of physical activity on insulin-related signaling within brain-derived vesicles.
The results
The findings indicated that participation in the two-week exercise program led to an increased number of neuronal extracellular vesicles carrying proteins associated with insulin sensitivity. Notably, higher levels of the protein Akt were detected in these vesicles following each exercise session. This increase became particularly pronounced after glucose consumption, suggesting that physical activity enhanced the brain’s insulin response when blood sugar levels rose. In essence, exercise appeared to improve the ability of brain cells to respond to insulin signals.
Improvements in overall blood sugar control were also observed following the exercise program. Enhanced peripheral insulin sensitivity was noted, indicating a more efficient use of insulin for blood sugar regulation. Notably, changes in the Akt protein within neuronal vesicles appeared to be linked to these metabolic benefits, including a modest reduction in body weight. These findings suggest a potential connection between exercise-induced adaptations 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,” stated Malin. “And we use these neuronal extracellular vesicles as an indicator of brain insulin sensitivity.”
Steven Malin
“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,” Malin explained. “It’s like playing the game telephone with a friend. At some point, the message gets lost when the brain becomes insulin resistant.”
Steven Malin
While this study offers valuable insights, certain limitations must be acknowledged. The participant group was relatively small, with most individuals being women. As a result, these findings may not be broadly applicable to larger, more diverse populations, including men and individuals of varying ages or health conditions. Additionally, the absence of a non-exercise control group limits direct comparisons, as baseline measurements served as the primary reference. Another consideration is that brain insulin sensitivity was inferred through changes in proteins within neuronal extracellular vesicles rather than through direct assessments of brain function or cognitive performance.
Further research should expand upon these findings by incorporating larger, more diverse participant groups, including a control group, and exploring the effects of varying exercise types and durations. Investigating the relationship between neuronal extracellular vesicle changes and actual cognitive improvements would be particularly valuable. Studies combining blood vesicle analysis with cognitive assessments and brain imaging could offer a more comprehensive understanding of how exercise supports brain health. Deeper insights into these mechanisms may contribute to the development of targeted exercise strategies aimed at preventing cognitive decline and promoting long-term brain health, particularly for individuals at risk of conditions such as type 2 diabetes and Alzheimer’s disease.
https://doi.org/10.1111/acel.14369
Summary
Short-term exercise may help reduce the risk of Alzheimer’s Disease and Related Dementia (ADRD) in adults with prediabetes by improving neuronal insulin signaling. This study examined the effects of a two-week supervised exercise program on insulin-related brain processes in 21 older adults (predominantly women, average age 60) with prediabetes. Participants engaged in either continuous or interval aerobic training for 60 minutes per session.
Following the intervention, improvements were observed in aerobic fitness (VO2peak), insulin sensitivity, and overall blood sugar control, alongside a slight reduction in body weight. Exercise also influenced neuronal extracellular vesicles (nEVs), small structures that carry signaling proteins between brain cells. Notably, an increase in glucose-stimulated Akt protein levels and a decrease in pro-BDNF—a protein involved in brain plasticity—were recorded. These findings suggest that exercise alters neuronal insulin signaling in response to glucose intake, which may contribute to reducing ADRD risk in individuals with prediabetes.