ArticleCPT: pharmacometrics & systems pharmacology2014
Effects of IL-1β-Blocking Therapies in Type 2 Diabetes Mellitus: A Quantitative Systems Pharmacology Modeling Approach to Explore Underlying Mechanisms.
Article in CPT: pharmacometrics & systems pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
What it found
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Who cites it
12 citing papers in PubMed, 19 citations in OpenAlex.
- Assessment of ImmobilizedFoods (Basel, Switzerland) · 2024Article
- Gestational Diabetes Mellitus-Induced Inflammation in the Placenta via IL-1β and Toll-like Receptor Pathways.International journal of molecular sciences · 2024Article
- Tipping-point transition from transient to persistent inflammation in pancreatic islets.NPJ systems biology and applications · 2024Article
- A data-driven computational model for obesity-driven diabetes onset and remission through weight loss.iScience · 2023Article
- Applications of Quantitative Systems Pharmacology in Model-Informed Drug Discovery: Perspective on Impact and Opportunities.CPT: pharmacometrics & systems pharmacology · 2019Article
- Quantitative Systems Pharmacology: An Exemplar Model-Building Workflow With Applications in Cardiovascular, Metabolic, and Oncology Drug Development.CPT: pharmacometrics & systems pharmacology · 2019Review
- A SIRT1 agonist reduces cognitive decline in type 2 diabetic rats through antioxidative and anti‑inflammatory mechanisms.Molecular medicine reports · 2019Article
- Article
- LASSIM-A network inference toolbox for genome-wide mechanistic modeling.PLoS computational biology · 2017Article
- Requirements for multi-level systems pharmacology models to reach end-usage: the case of type 2 diabetes.Interface focus · 2016Review
- The promises of quantitative systems pharmacology modelling for drug development.Computational and structural biotechnology journal · 2016Review
- BioModels: Content, Features, Functionality, and Use.CPT: pharmacometrics & systems pharmacology · 2015Article
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Recent clinical studies suggest sustained treatment effects of interleukin-1β (IL-1β)-blocking therapies in type 2 diabetes mellitus. The underlying mechanisms of these effects, however, remain underexplored. Using a quantitative systems pharmacology modeling approach, we combined ex vivo data of IL-1β effects on β-cell function and turnover with a disease progression model of the long-term interactions between insulin, glucose, and β-cell mass in type 2 diabetes mellitus. We then simulated treatment effects of the IL-1 receptor antagonist anakinra. The result was a substantial and partly sustained symptomatic improvement in β-cell function, and hence also in HbA1C, fasting plasma glucose, and proinsulin-insulin ratio, and a small increase in β-cell mass. We propose that improved β-cell function, rather than mass, is likely to explain the main IL-1β-blocking effects seen in current clinical data, but that improved β-cell mass might result in disease-modifying effects not clearly distinguishable until >1 year after treatment.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.