Stress has long been recognized as a contributor to various health issues, but a new study from Mount Sinai sheds light on a surprising biological pathway that may directly link stress to type 2 diabetes. Published in the journal Nature, the research identifies a neural circuit connecting the brain’s medial amygdala to the liver, which regulates blood glucose levels in response to stress. This discovery not only deepens our understanding of how stress affects the body but also opens potential new avenues for diabetes treatment and prevention.

The study, led by Dr. Sarah Stanley and Dr. Paul J. Kenny, offers a compelling explanation for how emotional stress can lead to elevated blood sugar levels. The medial amygdala, a region of the brain traditionally associated with processing emotions, was found to play a direct role in managing glucose production in the liver. This challenges the conventional view that only the hypothalamus and brain stem, centers known for maintaining bodily equilibrium, are responsible for blood glucose regulation.

In experiments conducted on mice, researchers observed that various forms of stress—including social and visual stressors—significantly increased activity in the medial amygdala. This heightened neural activity preceded a spike in blood glucose levels, suggesting a causal relationship. When researchers artificially activated medial amygdala neurons in mice that were not under stress, the animals still exhibited a 50 percent increase in blood glucose, reinforcing the idea that this brain region governs the body’s glycemic response to stress.

What makes this finding particularly noteworthy is the identification of a specific pathway: from the medial amygdala through the hypothalamus to the liver. Using viral tracing methods, the team demonstrated that activating this circuit nearly doubled the amount of glucose released by the liver. This mechanism appears to serve a natural purpose—providing a burst of energy in response to acute stress. However, when stress becomes chronic and is combined with a high-fat diet, the circuit’s output becomes dysregulated. The result is a persistent elevation in blood glucose, which can contribute to the development of type 2 diabetes.

According to the researchers, repeated stress exposure appears to desensitize this neural circuit. Over time, the medial amygdala’s response to stress diminishes, but the liver continues to overproduce glucose. This dysregulation mirrors conditions seen in prediabetes and type 2 diabetes, where the body struggles to maintain normal blood sugar levels. I found this detail striking—how a natural, adaptive response to stress can become maladaptive under continuous pressure, leading to chronic disease.

The implications for both medicine and public health are significant. Type 2 diabetes affects an estimated 500 million people worldwide, and stress is increasingly recognized as a major health concern. This study offers a biological explanation for the observed link between chronic stress and higher diabetes risk. It also underscores the importance of addressing social and environmental factors that contribute to stress, such as economic instability, discrimination, and social isolation.

Dr. Stanley noted that the findings reshape our understanding of the amygdala’s role. “Previously, we thought the amygdala only controls our behavioral response to stress—now, we know it controls bodily responses, too,” she explained. This broader perspective could influence how clinicians approach diabetes prevention and treatment, particularly in patients experiencing high levels of stress.

For clinicians, this research provides a clearer framework for understanding how psychological stress can translate into physiological changes that elevate disease risk. It also suggests that therapies aimed at modulating this brain-liver circuit could help improve glucose control in people with diabetes. This could be especially beneficial for those whose blood sugar levels are difficult to manage despite traditional interventions.

Looking ahead, the researchers plan to investigate the medial amygdala-to-liver circuit in greater detail. Future studies will aim to identify the specific neural cell types involved and examine how both short-term and long-term stress alter the circuit’s structure and gene expression. Another key question is whether reducing stress through behavioral or pharmacological means can reverse the circuit’s dysfunction and lower diabetes risk.

While the study was conducted in animal models, its findings provide a strong foundation for future human research. If similar mechanisms are found in people, it could lead to innovative treatments that target the brain’s stress response to manage or even prevent type 2 diabetes. In the meantime, the study adds weight to the growing consensus that managing stress is not just about mental well-being—it’s a crucial component of physical health as well.

This research was supported by the American Diabetes Association’s “Pathway to Stop Diabetes” Grant, along with funding from the National Institutes of Health and the Department of Defense. The Mount Sinai Health System, where the research was conducted, continues to lead in advancing scientific understanding of complex health conditions through interdisciplinary collaboration and cutting-edge methodologies.

As our understanding of the brain’s influence on bodily systems expands, so too does the potential for more holistic approaches to health. This study serves as a reminder that emotional and physical health are deeply interconnected, and that addressing one can have profound effects on the other.

Read more at mountsinai.org