Study links stress protein to poor metabolic regulation and risk of type 2 diabetes

A protein involved in the development of stress-related psychiatric disorders plays a role in metabolic problems that can precede type 2 diabetes, according to new research.
Researchers have known for some time that chronic stress promotes high levels of inflammation in the body, which accelerates the aging process and increases the risk of developing type 2 diabetes.
In the new study, scientists at the Max Planck Institute of Psychiatry reveal another biological mechanism linking a dysregulation of the stress system and that of various metabolic functions.
They have found that having high levels of a stress protein expressed in muscle appears to contribute to impaired glucose metabolism, and possibly insulin resistance.
The protein is called FK506-binding protein 51 (FKBP51) and is implicated in the development of mood disorders and anxiety.
The gene controlling the production of FKBP51 has been previously linked to a brain’s stress response (HPA axis hyperactivation) raising cortisol levels, which can impair mood and cause insulin resistance.
It was also previously shown that variations in the FKBP5 gene are associated with type 2 diabetes and markers of insulin resistance.
The new research focused on understanding the effect of the FKBP51 protein on glucose tolerance and insulin signalling in response to a metabolic stressor (hypercaloric feeding).
For this purpose, researchers studied two groups of mice on a high calorie, high-fat diet: one in which the animals had a functional FKBP51 gene and another lacking the gene.
After eight weeks, they found that mice that lacked the gene did not gain any weight despite the excessive calorie intake.
Earlier findings by the same team also show higher levels of FKBP51 expression lead to increased body weight gain when mice are under conditions of stress.
Mice in which the FKBP51 gene was silenced also had improved glucose tolerance and increased insulin signalling in muscle tissue.
The team has identified a compound able to counteract the action of FKBP51 called SAFit2, which could be used to improve glucose tolerance and body weight as part of new diabetes treatments.
The findings were published in the journal Nature Communications.