Preventing type 2 diabetes: When genes fail to respond

Regular physical activity is a highly effective means of lowering the risk of developing diabetes. However, patients respond in very different ways. In about one in five participants in so-called training intervention studies, the positive metabolic impact of physical exercise actually fails to occur.

A team of researchers led by Prof. Cora Weigert of the University Hospital Tübingen, who heads a department at the Institute of Diabetes Research and Metabolic Diseases (IDM), a research unit of the Helmholtz Zentrum München at the University of Tübingen, have now examined the reasons behind this.

To this end, 20 middle-aged subjects completed an endurance training program over eight weeks consisting of cycling and walking at the Sports Medicine in Tübingen (Head: Prof. Andreas Nieß). “All participants were at high risk to develop type 2 diabetes. The aim was to improve their insulin sensitivity and to lower their diabetes risk“, explains Dr. Anja Böhm from the IDM and first author of the study. “Before the training intervention, none of the participants were very physically active.”

Messenger substance inhibits glucose and fat burning

Together with Prof. Martin Hrabě de Angelis and Prof. Johannes Beckers from the Institute of Experimental Genetics (IEG), Helmholtz Zentrum München, the researchers examined molecular changes in the skeletal muscle. While the anticipated positive effects on genes important for glucose and fat burning were evident in the muscles of those participants whose insulin sensitivity had improved, the respective adjustments in the muscles of the “non-responders” were reduced.

However, analyses of the muscles of the “non-responding” participants revealed that the messenger substance TGF-beta* was activated after training. Experiments with human skeletal muscle cells subsequently conducted by Dr. Christoph Hoffmann of the University Hospital Tübingen confirmed that TGF-beta inhibits transcription of the genes that are important for glucose and fat burning and reduces insulin sensitivity.

No carte blanche for couch potatoes

“At the moment we are still trying to understand what causes TGF-beta to be activated in the muscle of some participants. There is some evidence that a different training program where the intensity or length of training is adapted to an individual’s ability to respond to physical exercise would be successful, and would help to prevent diabetes,” says Prof. Weigert. But the results should not be understood as a carte blanche for couch potatoes, she adds. “I myself am convinced that everyone – given a suitable training program – can lower their personal diabetes risk!”

Further information

Background:
* TGF-beta (Transforming Growth Factor beta) is a signaling molecule that belongs to the family of cytokines and plays an important role in tissue development and differentiation. In adult muscle, it is activated in the event of inflammations and injuries, and is involved in regeneration processes. However, chronic activation of TGF-beta leads to tissue fibrosis. Amongst other things, the study showed that expression of the PGC1α and AMPKα2 genes and the TFAM transcription factor was specifically affected by TGF-beta.

Original Publication:
Böhm, A. et al. (2016). TGFβ contributes to impaired exercise response by suppression of mitochondrial key regulators in skeletal muscle, Diabetes, DOI: 10.2337/db15-1723
http://diabetes.diabetesjournals.org/content/diabetes/early/2016/06/29/db15-1723…

The Helmholtz Zentrum München, the German Research Center for Environmental Health, pursues the goal of developing personalized medical approaches for the prevention and therapy of major common diseases such as diabetes and lung diseases. To achieve this, it investigates the interaction of genetics, environmental factors and lifestyle. The Helmholtz Zentrum München is headquartered in Neuherberg in the north of Munich and has about 2,300 staff members. It is a member of the Helmholtz Association, a community of 18 scientific-technical and medical-biological research centers with a total of about 37,000 staff members. http://www.helmholtz-muenchen.de/en

The primary research objective of the research groups working in the Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Zentrum München at the University of Tübingen is personalized prediction of diabetes risk and diabetes prevention as well as personalized therapy. Here special focus is placed on gene-environment interaction. http://www.helmholtz-muenchen.de/idm

Founded in 1805, the University Hospital Tuebingen is one of the leading centres of German university medicine. As one of 33 University Hospitals in Germany, it contributes to a successful combination of top-level medicine, research, and teaching. More than 400,000 in- and outpatients from around the world benefit from this connection of science and practice each year, since the clinics, institutes, and centres unite specialists from all fields under one roof. Its experts collaborate across disciplines and offer state-of-the-art research-based treatment to all patients. The University Hospital does research to improve diagnostics, therapies, and healing processes. Many new cutting-edge treatments are clinically tested and applied in Tuebingen. Neurosciences, Oncology and Immunology, Infection Biology, Vascular Medicine and Diabetes are focus areas of research at the University Hospital Tuebingen. It is a reliable partner in four of the six German Centres for Health Research (DZG) created by the Federal Government. http://www.medizin.uni-tuebingen.de/en

The German Center for Diabetes Research (DZD) is a national association that brings together experts in the field of diabetes research and combines basic research, translational research, epidemiology and clinical applications. The aim is to develop novel strategies for personalized prevention and treatment of diabetes. Members are Helmholtz Zentrum München – German Research Center for Environmental Health, the German Diabetes Center in Düsseldorf, the German Institute of Human Nutrition in Potsdam-Rehbrücke, the Paul Langerhans Institute Dresden of the Helmholtz Zentrum München at the University Medical Center Carl Gustav Carus of the TU Dresden and the Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Zentrum München at the Eberhard-Karls-University of Tuebingen together with associated partners at the Universities in Heidelberg, Cologne, Leipzig, Lübeck and Munich. http://www.dzd-ev.de/en/index.html

Contact for the media:
Department of Communication, Helmholtz Zentrum München – German Research Center for Environmental Health, Ingolstädter Landstr. 1, 85764 Neuherberg – Tel. +49 89 3187 2238 – Fax: +49 89 3187 3324 – E-mail: presse@helmholtz-muenchen.de

Scientific Contact at Helmholtz Zentrum München:
Prof. Dr. Cora Weigert, Helmholtz Zentrum München – German Research Center for Environmental Health, Institute of Diabetes Research and Metabolic Diseases, and University Hospital Tübingen, Otfried-Müller-Straße 10, 72076 Tübingen – Tel. +49 7071 2985670, E-mail: cora.weigert@med.uni-tuebingen.de

https://www.helmholtz-muenchen.de/en/press-media/press-releases/2016/index.html