A new study in mice shows how chronic stress leads to an improper glucose response and metabolic disorders

By Laniah Bowdery

Stress is known to lead to Type 2 Diabetes and other disorders, called metabolic disorders, which affect the body’s ability to process energy. The reason why stress precedes metabolic disorders is less widely known. Now, new findings report that the link between stress and metabolic disorders may be due to an understudied bridge between the nervous system and the digestive system.      

A study in mice, published in September 2025 in the journal Nature by a team of researchers at Icahn School of Medicine at Mount Sinai, suggests a new perspective on metabolic disorders. The study finds that chronic stress changes the body’s ability to regulate the amount of glucose in the blood stream. The medial amygdala (MeA), a tiny part of a small region in the brain, controls stress responses. MeA neurons send signals throughout the body that change glucose levels in response to stress, and that repeated stress changes the body’s ability to regulate blood glucose levels. The study finds the link between stress and metabolism in the pathway from the MeA neurons, to the rest of the brain, and then to the body’s response signals in the liver.

 “I think that there’s a huge amount of knowledge that the amygdala is switched on in stressful situations, and it’s known to have this role in influencing the behavioral response to stress,” says Sarah Stanley, an Associate Professor of Medicine in the Division of Endocrinology, Diabetes and Bone Disease and the senior author on the study. “But I think what our studies hopefully add is the fact that it’s sort of this less well understood part of the amygdala. It’s a very complicated region – the medial amygdala also plays a role in controlling the sort of bodily response to stress, in particular the glucose response.”

To assess the link between the amygdala and blood glucose levels, mice were put into controlled conditions and groups based on their body weight. Researchers exposed mice to different stressors: physical, restraint, territorial, and visual. The glucose levels of the mice and activity of MeA neurons were studied throughout these exposures.

The study provides context for how certain metabolic processes affect survival behaviors. These behaviors include routines such as migration, communication, foraging, and more. When an animal encounters a threat, it must use energy for the appropriate flight or fight responses. The MeA neurons would send a signal from the brain to the liver to fuel responses from the muscles and the heart while also supporting the use of brain power to process the response needed to understand the threat. So, changes to the amount of glucose in the blood sugar occur during fight or flight behaviors. Stress leads to dysregulated blood glucose which can lead to metabolic disorders if the stress is repeated.

 “We wanted to know first whether or not these neurons in the medial amygdala were switched on with stress,” Stanley says. “So, we tried to come up with a sort of range of different stress that might perhaps have different, possibly different mechanisms.” Mice on high fat diets were put into different kinds of stressful situations. The results did not change much depending on the kind of situation the mice were put in.

“If we talk about stress, it’s a sort of disturbance of the system. Anything that would annoy us or an animal, picture as a stressor,” says Michael van der Kooij, an assistant professor and behavioral neuroscientist at UMC Utrecht, who was not involved in the study. “But then we always think of the early response, say the sympathetic nervous system so adrenaline or adrenaline heart rate goes up and it’s mostly also linked to pro inflammatory processes, but where does it turn to being chronic?”

The study is one of the first of its kind to explore the medial amygdala and the role that It plays in metabolic processes in response to stress. It begins to answer the question of where and whether glucose fluctuations in response to stress become a chronic issue. It turns out that the stress starts in the amygdala, heads to the liver, and ends with a body unable to properly process glucose.

Finding the cause of stress-induced metabolic disorders is important to future treatment and preventive care. Before, most studies focused on the hypothalamic–pituitary–adrenal stress systems. These are the organs originally known release hormones to manage stress. This study introduces something new to the conversation by researching the medial amygdala. Future researchers can follow the MeA neurons and their link to the liver. Looking closer at the links between stress and metabolic disorders is more prevalent now than ever as 10.44% or over 34 million people in the United States have type 2 diabetes.