Scientists investigate a new lead in the search for better diabetes treatments.
Insulin resistance occurs when muscles, liver, and fat cells become unable to use insulin appropriately, which ultimately leads to a dangerous rise in blood glucose levels.
Now, researchers from the Max Planck Institute of Psychiatry in Munich, Germany, have found that a protein called FKBP51 may also play a role in triggering type 2 diabetes.
The protein has so far been associated with anxiety and depression; it contributes to the regulation of the stress system. When the gene that controls the production of FKBP51 suffers a mutation, this can lead to dysregulation of the stress system, which, in turn, can cause mental health disorders.
Mathias Schmidt — lead researcher of the current study — and colleagues have recently noted that the FKBP51 protein also contributes to forming a molecular link between the stress system and the regulation of various metabolic functions. This may make FKBP51 responsible for the onset of metabolic diseases such as obesity and diabetes.
The team’s findings have now been published in the journal Nature Communications.
Protein reacts to metabolic stress
Schmidt and team looked at a mouse model to understand the potential role played by FKBP51 in metabolic processes. They studied the effect of a high-fat diet on mice in which the FKBP51 gene was expressed, as well as on knockout mice, in which that gene was inactivated artificially.
They found that the knockout mice did not gain weight after exposure to the diet, had better glucose, or blood sugar, tolerance, and had more effective insulin signaling.
This allowed the researchers to understand that the FKBP51 protein — regulated by the gene with the same name — affects signaling pathways in skeletal muscles.
Since the protein is sensitive to metabolic stress factors, such as high fat intake, it can ultimately lead to blood sugar buildup and insulin resistance.
These are the main factors to blame in the development of type 2 diabetes and obesity.
“FKBP51 influences a signaling cascade in muscle tissue, which with excessive calorie intake leads to the development of glucose intolerance, i.e., the key indicator of diabetes type 2.”
The cause may lead to the treatment
Fortunately, this mechanism has also offered the scientists an insight into how they might be able to prevent FKBP51’s response to the stressors created by a high-fat diet.
The answer, they say, lies in SAFit2, which is an FKBP51 antagonist compound, or a chemical able to block the action of the stress protein.
Ongoing treatment with SAFit2, Schmidt and colleagues explain, could imitate the effect of the inactivated gene in knockout mice, leading to better “body weight regulation and glucose tolerance,” thus preventing the onset of diabetes.
SAFit2 was developed by Felix Hausch, formerly of the Max Planck Institute of Psychiatry, who now works at the University of Darmstadt in Germany.
The researchers plan on continuing to improve the compound and testing it in future clinical trials, in the hope that this may lead to new and more effective treatments for diabetes and other metabolic disorders.
“These findings may provide a completely new treatment approach for diabetes and other metabolic diseases,” says Alon Chen, director of the Max Planck Institute of Psychiatry.
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