Study: How Stress and Diet Disrupt a Brain Circuit to Increase Diabetes Risk

New study findings from researchers at Mount Sinai discovered a brain circuit that connects stress to an increase in blood sugar, which may help explain the link between stress and type 2 diabetes (T2D).

The study authors, who published their findings in Nature, noted that the circuit, which runs from the amygdala to the liver, provides a burst of energy to help manage stressful situations; however, when a high-fat diet and chronic stress are added, it can disrupt the circuit, leading to an overproduction of glucose in the liver. This can cause long-term elevated blood sugar, known as hyperglycemia, which is a key risk factor for developing T2D.^1,2

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Mental Health and Diabetes

According to the CDC, untreated mental health issues can worsen diabetes, and problems with diabetes can make an individual’s mental health issues decline. Specifically, when an individual is stressed, it can be harder to take care of themselves, and blood sugar levels can be affected as stress hormones cause them to fluctuate.

Stress from illness or injury, when added to the above conditions, can make blood sugar levels rise. Prolonged stress can also lead to or worsen other health issues. Anxiety, or the mind and body’s reaction to stress, is more common in individuals with diabetes, who are 20% more likely to experience it.³

“The impact of stress on diabetes is enormous. But it’s not just diabetes: stress has broader impacts on many other conditions. This means that addressing the social determinants that contribute to stress may improve health, including diabetes.” Sarah Stanley, MBBCh, PhD, associate professor, co-director, Human Islet and Adenovirus Core, Diabetes, Obesity and Metabolism Institute, and The Friedman Brain Institute at Mount Sinai, said in a news release.²

Understanding Brain Activity in the Amygdala

Research around the amygdala’s involvement in the metabolic changes that provide the quick release of energy is not understood. To better understand how stress affects brain activity in the amygdala, the investigators monitored the neural activity in the medial amygdala of mice.

Initial findings demonstrated that various types of stress, including social and visual, increased the activity in the medial amygdala, causing the mice’s blood glucose levels to increase.^1,2 The researchers then activated the medial amygdala in unstressed mice and were able to replicate the same rise in glucose levels that related to stress, without inducing any behavioral changes.

After tracing neural pathways, the researchers found that stress activates neurons that connect the medial amygdala to the hypothalamus to the liver, which releases more glucose.^1,2

The results demonstrated that blood glucose rapidly rose by 70% when exposed to acute stressors. When mice were exposed to stress, the activity of their medial amygdala neurons doubled. Further results found that a combination of repeated stress and a high-fat diet could alter the circuit, causing a long-term increase in blood glucose, even after stress was no longer a factor.^1,2

The findings suggest that repeated stress disrupts this specific brain circuit, leading to an increase in glucose released by the liver.^1,2

“The results of this study not only change how we think about the role of stress in diabetes, but also how we think about the role of the amygdala. Previously, we thought the amygdala only controlled our behavioral response to stress—now, we know it controls bodily responses, too,” Stanley said in the news release.²

REFERENCES

1. Carty, J.R.E., Devarakonda, K., O’Connor, R.M. et al. Amygdala–liver signalling orchestrates glycaemic responses to stress. Nature (2025). https://doi.org/10.1038/s41586-025-09420-1

2. A Mount Sinai study discovers potential link between stress and type 2 diabetes. EurekAlert! News release. September 3, 2025. Accessed September 11, 2025. https://www.eurekalert.org/news-releases/1096792

3. Diabetes and Mental Health. CDC. News release. May 15, 2024. Accessed September 11, 2025. https://www.cdc.gov/diabetes/living-with/mental-health.html