Effects of IL-1β-Blocking Therapies in Type 2 Diabetes Mellitus: A Quantitative Systems Pharmacology Modeling Approach to Explore Underlying Mechanisms.

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 fu

SUBMITTER: Palmer R 

PROVIDER: S-EPMC4076803 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature