Gene that ties stress to diabetes, depression identified

Researchers have identified the gene changes in whose activity due to stress cause anxiety disorders and depression, as well as metabolic disorders like obesity, type 2 diabetes and arteriosclerosis.

These diseases, linked to stress, are reaching epidemic proportions.

Alon Chen of the Weizmann Institute’s Neurobiology Department and his research team have now discovered that changes in the activity of a single gene in the brain not only cause mice to exhibit anxious behaviour but also lead to metabolic changes that cause the mice to develop symptoms associated with type 2 diabetes.

All of the body’s systems are involved in the stress response, which evolved to deal with threats and danger.

Behavioural changes tied to stress include heightened anxiety and concentration, while other changes in the body include heat generation, changes in the metabolism of various substances and even changes in food preferences.

What ties all of these things together? The Weizmann team suspected that a protein known as Urocortin-3 (Ucn3) was involved.

This protein is produced in certain brain cells, especially in times of stress, and it is known to play a role in regulating the body’s stress response.

The researchers developed a new, finely-tuned method for influencing the activity of a single gene in one area in the brain, using it to increase the amounts of Ucn3 produced in just that location.

They found that heightened levels of the protein produced two different effects: The mice’s anxiety-related behaviour increased, and their bodies underwent metabolic changes as well.

With excess Ucn3, their bodies burned more sugar and fewer fatty acids, and their metabolic rate sped up. These mice began to show signs of the first stages of type 2 diabetes.

A drop in muscle sensitivity to insulin delayed sugar uptake by the cells, resulting in raised sugar levels in the blood. Their pancreas then produced extra insulin to make up for the perceived ‘deficit’.

“We showed that the actions of single gene in just one part of the brain can have profound effects on the metabolism of the whole body,” says Chen.

This mechanism points the way toward the treatment or prevention of a number of stress-related diseases, a Weizmann Institute release says.

The findings were published online this week in the Proceedings of the National Academy of Sciences (PNAS).