Protection and Regeneration of Beta Cells
Michele Solimena | Heiko Lickert | Annette Schürmann
The beta cells of Langerhans' islets in the pancreas produce and store insulin. In type 1 diabetes and in advanced stages of type 2 diabetes, however, the beta cells die, so that not enough insulin can be produced. The DZD is working on methods to better protect the insulin-producing beta cells and to restore or replace them.
The Academy focuses on translational and multicenter studies that combine the strengths of the DZD partners in islet cell biology. The researchers investigate molecular mediators that lead to beta cell failure and work on ways and molecular approaches for new diabetes therapies, the implementation of cell replacement therapy in type 1 diabetes patients, and the regeneration of functional beta cell mass.
The main focus areas are:
- Improving understanding of the natural course of type 2 diabetes in human beta cells
- Clarification of the influence of organ cross-talk on the function of beta cells
- Development of strategies for the replacement and regeneration of beta cells
- Investigation of new approaches for the protection and regeneration of beta cells with dextromethorphan derivatives
With the "Human Islet Biobank", the DZD has a unique biobank with human pancreatic tissue samples. The biobank contains pancreatic tissue from metabolically characterized patients who have undergone complete or partial pancreatectomy. In 2019, the biobank was expanded to include pancreatic fat cells.
In studies on fatty tissue in the pancreas, the researchers showed that mice that are susceptible to diabetes had significantly higher fat and triglyceride levels in the pancreas than diabetes-resistant mice of the same species.
Targeted prevention and early treatment of certain subgroups of people with diabetes is a step towards precision medicine in the form of specifically adapted forms of therapy to delay or even avoid secondary diseases.
Current research results
One focus of the Academy is the development of beta cell replacement therapies. DZD scientists have shown that the formation of beta cells from pluripotent stem cells functions better if they are cultivated in 3D cell aggregates at an early stage. Furthermore, several factors were discovered that trigger the expansion, differentiation and maturation of beta cells. These results are not only essential for the generation of functional beta cells in culture for modeling and cell replacement therapy, but also attractive targets for the in vivo regeneration of lost beta cell mass in diabetes patients.
Inceptor counteracts insulin signalling in β-cells to control glycaemia. Nature (2021), DOI: 10.1038/s41586-021-03225-8
Multi-omics profiling of living human pancreatic islet donors reveals heterogeneous beta cell trajectories toward type 2 diabetes. Nature Metabolism (2021). DOI: 10.1038/s42255-021-00420-9
Peripherally active dextromethorphan derivatives lower blood glucose levels by targeting pancreatic islets. Cell Chemical Biology (2021). DOI: https://doi.org/10.1016/j.chembiol.2021.05.011
Generation of pancreatic β cells from CD177+ anterior definitive endoderm. Nature Biotechnology (2020), DOI: 10.1038/s41587-020-0492-5
Dysfunction of Persisting β-Cells is a Key Feature of Early Type 2 Diabetes Pathogenesis. Cell Reports (2020), DOI:https://doi.org/10.1016/j.celrep.2020.03.033
Targeted pharmacological therapy restores β-cell function for diabetes remission. Nature Metabolism (2020), DOI: 10.1038/s42255-020-0171-3.
Prof. Dr. Dr. Michele Solimena, Head DZD Academy Beta Cells
Talk at the 10th anniversary celebration of the DZD on June 24, 2019 in Berlin (in English).
Members of the Academy
Tiago Cardoso Alves, PLID
Mostafa Bakhti, HMGU
Bengt Belgardt, DDZ
Volker Burkart, DDZ
Stefan Bornstein, PLID
Ünal Coskun, PLID
Anthony Gavalas, PLID
Felicia Gerst, IDM
Anne Grapin-Botton, MPID
Tilman Grune, DIfE
Eckhard Lammert, DDZ
Heiko Lickert, HMGU
Barbara Ludwig, PLID
Nikolay Ninov, PLID
Annette Schürmann, DIfE
Henrik Semb, HMGU
Michele Solimena, PLID
Stephan Speier, PLID
Robert Wagner, DDZ
Thilo Welsch, PLID
Eckhard Wolf, LMU