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In the human body, beta cells are found in the pancreas, which regulate the sugar balance by producing and releasing insulin into the blood. They therefore represent an important aspect of research into diabetes. For ethical reasons, animal experiments are to be avoided in the future, which is why efficient simulation methods are currently researched in the biological-medical field for a variety of issues. In this interdisciplinary area, we work together with institutes from the biological and medical fields.
In particular, microscopy and concentration measurements from the research partner institutions were incorporated into the development of various problem-specific models. One example is a cellular automaton that describes the transport of insulin granules through the cell. This transport process and the release of insulin into the blood are significantly linked to highly dynamically changing ion concentrations inside and outside the cell. In this context, our goal is the holistic modeling and simulation of this metabolism and its interactions.
Against this background, a further cellular automaton was developed that depicts the dynamics of fusion, division and transport processes of mitochondrial networks. They convert glucose from the blood into ATP and thus represent the most important driving force of cell metabolism. These processes were modeled using a set of nonlinear differential equations on the one hand and spatially resolved reaction-diffusion equations on the other. The results show very good agreement with the corresponding measurements.
[1] Michael Müller, Mathias Glombek, Jeldrick Powitz, Dennis Brüning, Ingo Rustenbeck. A Cellular Automaton Model as a First Model-Based Assessment of Interacting Mechanisms for Insulin Granule Transport in Beta Cells, Cells, 2020 https://doi.org/10.3390/cells9061487
[2] Bastian Haus, Dennis Brüning, Sofie Groß, Michael Müller, Ingo Rustenbeck. The chainging view of insulin granule mobility: From conveyor belt to signaling hub, Frontiers in Endocrinology, 2022 doi.org/10.3389/fendo.2022.983152
[3] Michael Müller, Jonas Walkling, Nele Seemann, Ingo Rustenbeck. The Dynamics of Calcium Signaling in Beta Cells—A Discussion on the Comparison of Experimental and Modelling Data, International Journal of Molecular Sciences, 2023 https://doi.org/10.3390/ijms24043206
[4] Sara Langer, David Jagdhuhn, Rica Waterstradt, Jessica Gromoll, Michael Müller, Matthew G. Rees, Anna L. Gloyn, Simone Baltrusch. Effects of coding variants in the glucokinase regulatory protein gene on hepatic glucose and triglyceride metabolism suggest a gene regulatory function of glucokinase, Metabolism, 2025 https://doi.org/10.1016/j.metabol.2025.156150
[5] Lars de Jong, Paula Clasen, Michael Müller, Ulrich Römer. Uncertainty analysis of limit cycle oscillations in nonlinear dynamical systems with the Fourier generalized Polynomial Chaos, Journal of Sound and Vibration, 2025 https://doi.org/10.1016/j.jsv.2025.119017