The marker Flattop subdivides the insulin-producing beta cells of the pancreas into those that maintain glucose metabolism and into immature cells that divide more frequently and adapt to metabolic changes. This could provide a starting point for regenerative diabetes therapies, as scientists of Helmholtz Zentrum München, in collaboration with colleagues of the Technical University of Munich and the German Center for Diabetes Research (DZD), report in the journal ‘Nature’.
The beta cells of the pancreas produce the metabolic hormone insulin when blood glucose levels rise, in order to keep glucose levels in equilibrium. If the beta cells are destroyed or lose their function, this can lead to serious diseases such as diabetes. However, not all beta cells are identical.
“It has long been known that there are different subpopulations of beta cells,” said Professor Heiko Lickert, director of the Institute of Diabetes and Regeneration Research at Helmholtz Zentrum München. “But until now, the underlying molecular mechanisms have remained elusive.”
Flattop is a marker for mature beta cells
In the current study, the researchers led by Lickert searched for molecular markers subdividing the respective subgroups. One molecule, in particular, captivated their attention: the protein Flattop.* It was present in about 80 percent of all beta cells. These cells effectively determined the glucose concentration of their environment and secreted the corresponding amount of insulin, thus showing the metabolic properties of mature beta cells.
Cells without Flattop proliferate more frequently
Conversely, the team of researchers observed that beta cells in which no Flattop was measurable showed a particularly high rate of proliferation. “In our experimental model, these cells proliferated up to four times more often than the Flattop-positive cells,” said study leader Lickert.
A type of precursor cells?
To pursue the hypothesis that the actively dividing cells (without Flattop) could be precursors of metabolically active cells, the scientists made use of a genetic trick to map the fate of single cells. This so called lineage tracing revealed that the proliferative progenitor cells were able to develop into mature beta cells with metabolic properties. This was also the case, when the scientists placed them in an artificial mini-organ-like 3D environment. Moreover, genetic analyses confirmed that in beta cells without Flattop, primarily genes responsible for sensing the environment were expressed, while in cells with Flattop primarily classic metabolic programs took place.
“Our results suggest that the Flattop-negative cells are a kind of immature reserve pool, which constantly renews itself and can replenish the mature beta cells,” Lickert said. According to the study leader this new possibility of subdividing these two subgroups allows a comprehensive analysis of the signaling pathways involved. The results of the researchers raise hopes for the development of regenerative therapies: “The heterogeneity of the beta cells has been studied for more than 50 years, now with enabling technologies it looks like we are beginning to understand how the cells behave,“ said Lickert.
In the future, the scientist will focus on two major aspects: on the one hand in terms of regenerative therapy their goal would be to regenerate endogenous beta cells in a targeted manner to replace dysfunctional or lost cells in patients. On the other hand the findings are a milestone in the generation of functional beta cells from stem cells in cell culture for cell replacement therapy, which was not possible so far.
* Flattop is part of the Wnt signaling pathway, which in particular regulates the development of tissues and cell functions.
**Lineage tracing is a method to map the fate of single cells. It is based on gene variants emitting a color signal upon induction of the respective gene. In this particular case cells without Flattop were colored in red and turned into green upon Flattop induction.
Bader, E. et al. (2016). Identification of proliferative and mature β-cells in the islet of Langerhans, Nature, DOI: 10.1038/nature18624
Corresponding reviews of the research group:
Migliorini, A. et al. (2016). Impact of islet architecture on beta cell heterogeneity, plasticity and function, Diabetologia, doi: 10.1007/s00125-016-3949-9
Roscioni, S. et al. (2016). Impact of islet architecture on beta cell heterogeneity, plasticity and function, Nature Reviews Endocrinology, in press
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 research activities of the Institute of Diabetes and Regeneration Research (IDR) focus on the biological and physiological study of the pancreas and/or the insulin producing beta cells. Thus, the IDR contributes to the elucidation of the development of diabetes and the discovery of new risk genes of the disease. Experts from the fields of stem cell research and metabolic diseases work together on solutions for regenerative therapy approaches of diabetes. The IDR is part of the Helmholtz Diabetes Center (HDC). http://www.helmholtz-muenchen.de/en/idr/index.html
Technical University of Munich (TUM) is one of Europe’s leading research universities, with more than 500 professors, around 10,000 academic and non-academic staff, and 39,000 students. Its focus areas are the engineering sciences, natural sciences, life sciences and medicine, reinforced by schools of management and education. TUM acts as an entrepreneurial university that promotes talents and creates value for society. In that it profits from having strong partners in science and industry. It is represented worldwide with a campus in Singapore as well as offices in Beijing, Brussels, Cairo, Mumbai, San Francisco, and São Paulo. Nobel Prize winners and inventors such as Rudolf Diesel, Carl von Linde, and Rudolf Mößbauer have done research at TUM. In 2006 and 2012 it won recognition as a German "Excellence University." In international rankings, TUM regularly places among the best universities in Germany. http://www.tum.de/en/homepage
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
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: email@example.com
Scientific Contact at Helmholtz Zentrum München:
Prof. Dr. Heiko Lickert, Helmholtz Zentrum München - German Research Center for Environmental Health, Institute of Diabetes and Regeneration Research, Parkring 11, 85748 Garching - Tel. +49 89 3187 3867, E-mail: firstname.lastname@example.org
Other press releases of Helmholtz Zentrum München:
Sonja Opitz | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt
Transport of molecular motors into cilia
28.03.2017 | Aarhus University
Asian dust providing key nutrients for California's giant sequoias
28.03.2017 | University of California - Riverside
The Institute of Semiconductor Technology and the Institute of Physical and Theoretical Chemistry, both members of the Laboratory for Emerging Nanometrology (LENA), at Technische Universität Braunschweig are partners in a new European research project entitled ChipScope, which aims to develop a completely new and extremely small optical microscope capable of observing the interior of living cells in real time. A consortium of 7 partners from 5 countries will tackle this issue with very ambitious objectives during a four-year research program.
To demonstrate the usefulness of this new scientific tool, at the end of the project the developed chip-sized microscope will be used to observe in real-time...
Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.
The results will be published on March 22 in the journal „Astronomy & Astrophysics“.
Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...
Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.
Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...
In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...
20.03.2017 | Event News
14.03.2017 | Event News
07.03.2017 | Event News
28.03.2017 | Life Sciences
28.03.2017 | Information Technology
28.03.2017 | Physics and Astronomy