Research Projects (Third party funds)

Project

Inflammation signals in type 2 diabetes

The activation of the innate immune system and chronic low-grade inflammation are closely associated with the pathogenesis of type 2 diabetes. Clinical trials based on anti-inflammation drugs are in progress with inconsistent results. Mathematical models, integrating and describing accurately information from different aspects, can help to understand the mechanisms and predict possible outcomes of specific treatments. IL-1beta is an interesting molecule in this context, because, on the one hand, it is a pro-inflammatory molecule, and, on the other hand, it is produced by pancreatic betacells and influences their activity. This gives rise to an interesting interaction between inflammation and insulin secretion.

Together with Kathrin Maedler (Bremen, Germany) and Michele Solimena (Dresden, Germany) we developed a mathematical model of IL-1beta dynamics in order to understand the onset of type 2 diabetes. The model solutions showed a structure well corresponding to the stages seen in type 2 diabetes development. The model suggested that only a treatment combining glucose control with transient anti-inflammatory drugs would provide a long-term control of type 2 diabetes. Together with Carlos Guzman (HZI) and Ingo Schmitz (Magdeburg, Germany) we currently focus on liver insulin resistance in the context of pulsatile insulin and inflammatory signals. This may contribute to a model including glucose, fatty acid and inflammation as key players in the development of type 2 diabetes. 

States of type 2 diabetes in silico. (A) Steady-state analysis: Full lines correspond to the healthy (green), diabetic (red), and advanced diabetic states, whereas the dotted lines are unstable…

Simm members

Sebastian C. Binder, Michael Meyer-Hermann, Gang Zhao, Azadeh Ghanbari (until 2017)

Publications

Zhao G, Dharmadhikari G, Maedler K, Meyer-Hermann M. Possible role of interleukin-1β in type 2 diabetes onset and implications for anti-inflammatory therapy strategies. PLoS Comput Biol10 (2014) e1003798.

Funding:

Helmholtz International Graduate School for Infection Research

EU-Marie-Curie Fellowship

BMBF-GerontoSys initiative (GerontoShield)

HFSP

BMBF-eMED: SYSIMIT

SYS-Stomach

Helmholtz Association cross-program activity "Metabolic Dysfunction and Human Disease"

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