Summary: A protein associated with anxiety and depression has been found to act as a link between the stress regulatory system and metabolic processes, research report.

Source: Max Planck Institute.

For the first time, scientists from the Max Planck Institute of Psychiatry in Munich could prove that a stress protein found in muscle has a diabetes promoting effect. This finding could pave the way to a completely new treatment approach.

For some time, researchers have known that the protein FKBP51 is associated with depression and anxiety disorders. It is involved in the regulation of the stress system – when the system does not function properly; mental disorders may develop. Now, researchers at the Max Planck Institute of Psychiatry have discovered a new, surprising role for this protein: It acts as a molecular link between the stress regulatory system and metabolic processes in the body.

“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,” project leader Mathias Schmidt summarizes. An unhealthy diet, rich in fat means stress for the body. If FKBP51 is increasingly produced in the muscle it leads to reduced absorption of glucose – as a result, diabetes and obesity may develop.

If FKBP51 is blocked, diabetes will not develop, even if too many calories are consumed or the body is still stressed. Less FKBP51 in the muscle tissue means reduced glucose intolerance and thus maintenance of normal metabolism.





Antagonist provides novel treatment approach

The protein FKBP51 can be pharmacologically blocked by antagonist compounds that were developed at the Max Planck Institute by Felix Hausch (presently at University of Darmstadt). In collaboration with the scientists at the Technical University Darmstadt and funded by the Bavarian State Ministry of Economic Affairs and Media, Energy and Technology, these compounds will be further developed for use in clinical trials. “These findings may provide a completely new treatment approach for diabetes and other metabolic diseases,” states Alon Chen, Director at the Max Planck Institute of Psychiatry.

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Source: Max Planck Institute

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Original Research: Full open access research for “Stress-responsive FKBP51 regulates AKT2-AS160 signaling and metabolic function” by Georgia Balsevich, Alexander S. Häusl, Carola W. Meyer, Stoyo Karamihalev, Xixi Feng, Max L. Pöhlmann, Carine Dournes, Andres Uribe-Marino, Sara Santarelli, Christiana Labermaier, Kathrin Hafner, Tianqi Mao, Michaela Breitsamer, Marily Theodoropoulou, Christian Namendorf, Manfred Uhr, Marcelo Paez-Pereda, Gerhard Winter, Felix Hausch, Alon Chen, Matthias H. Tschöp, Theo Rein, Nils C. Gassen & Mathias V. Schmidt in Nature Communications. Published online November 23 2017 doi:10.1038/s41467-017-01783-y

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[cbtabs][cbtab title=”MLA”]Max Planck Institute “Anti-Stress Compound Reduces Obesity and Diabetes Risk.” NeuroscienceNews. NeuroscienceNews, 13 December 2017.

<https://neurosciencenews.com/fkbp51-diabetes-obesity-8186/>.[/cbtab][cbtab title=”APA”]Max Planck Institute (2017, December 13). Anti-Stress Compound Reduces Obesity and Diabetes Risk. NeuroscienceNews. Retrieved December 13, 2017 from https://neurosciencenews.com/fkbp51-diabetes-obesity-8186/[/cbtab][cbtab title=”Chicago”]Max Planck Institute “Anti-Stress Compound Reduces Obesity and Diabetes Risk.” https://neurosciencenews.com/fkbp51-diabetes-obesity-8186/ (accessed December 13, 2017).[/cbtab][/cbtabs]

Abstract

Stress-responsive FKBP51 regulates AKT2-AS160 signaling and metabolic function

The co-chaperone FKBP5 is a stress-responsive protein-regulating stress reactivity, and its genetic variants are associated with T2D related traits and other stress-related disorders. Here we show that FKBP51 plays a role in energy and glucose homeostasis. Fkbp5 knockout (51KO) mice are protected from high-fat diet-induced weight gain, show improved glucose tolerance and increased insulin signaling in skeletal muscle. Chronic treatment with a novel FKBP51 antagonist, SAFit2, recapitulates the effects of FKBP51 deletion on both body weight regulation and glucose tolerance. Using shorter SAFit2 treatment, we show that glucose tolerance improvement precedes the reduction in body weight. Mechanistically, we identify a novel association between FKBP51 and AS160, a substrate of AKT2 that is involved in glucose uptake. FKBP51 antagonism increases the phosphorylation of AS160, increases glucose transporter 4 expression at the plasma membrane, and ultimately enhances glucose uptake in skeletal myotubes. We propose FKBP51 as a mediator between stress and T2D development, and potential target for therapeutic approaches.

“Stress-responsive FKBP51 regulates AKT2-AS160 signaling and metabolic function” by Georgia Balsevich, Alexander S. Häusl, Carola W. Meyer, Stoyo Karamihalev, Xixi Feng, Max L. Pöhlmann, Carine Dournes, Andres Uribe-Marino, Sara Santarelli, Christiana Labermaier, Kathrin Hafner, Tianqi Mao, Michaela Breitsamer, Marily Theodoropoulou, Christian Namendorf, Manfred Uhr, Marcelo Paez-Pereda, Gerhard Winter, Felix Hausch, Alon Chen, Matthias H. Tschöp, Theo Rein, Nils C. Gassen & Mathias V. Schmidt in Nature Communications. Published online November 23 2017 doi:10.1038/s41467-017-01783-y

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