title: Possible role of interleukin-1β in type 2 diabetes onset and implications for anti-inflammatory therapy strategies.
abstract: Increasing evidence of a role of chronic inflammation in type 2 diabetes progression has led to the development of therapies targeting the immune system. We develop a model of interleukin-1β dynamics in order to explain principles of disease onset. The parameters in the model are derived from in vitro experiments and patient data. In the framework of this model, an IL-1β switch is sufficient and necessary to account for type 2 diabetes onset. The model suggests that treatments targeting glucose bear the potential of stopping progression from pre-diabetes to overt type 2 diabetes. However, once in overt type 2 diabetes, these treatments have to be complemented by adjuvant anti-inflammatory therapies in order to stop or decelerate disease progression. Moreover, the model suggests that while glucose-lowering therapy needs to be continued all the way, dose and duration of the anti-inflammatory therapy needs to be specifically controlled. The model proposes a framework for the discussion of clinical trial outcomes.
authors.affiliation: Department of Systems Immunology and Braunschweig Integrated Centre of Systems Biology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
authors.forename: Gang
authors.initials: G
authors.lastname: Zhao
authors.affiliation: Centre for Biomolecular Interactions Bremen, University of Bremen, Bremen, Germany.
authors.forename: Gitanjali
authors.initials: G
authors.lastname: Dharmadhikari
authors.affiliation: Centre for Biomolecular Interactions Bremen, University of Bremen, Bremen, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Maedler
authors.affiliation: Department of Systems Immunology and Braunschweig Integrated Centre of Systems Biology, Helmholtz Centre for Infection Research, Braunschweig, Germany; Institute of Biochemistry, Biotechnology and Bioinformatics, Technische Universität Braunschweig, Braunschweig, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Meyer-Hermann
mesh_terms: D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D053590:Interleukin 1 Receptor Antagonist Protein / Q000378:metabolism; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000378:metabolism*; D018448:Models, Immunological
chemical_list: D000893:Anti-Inflammatory Agents; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D053590:Interleukin 1 Receptor Antagonist Protein; D053583:Interleukin-1beta