Modelling of detailed insulin receptor kinetics affects sensitivity and noise in the downstream signalling pathway

Camilla Luni, Kevin R. Sanft, Linda R. Petzold, Francis J. Doyle

Research output: Chapter in Book/Report/Conference proceedingConference contribution

1 Scopus citations

Abstract

Insulin resistance is a primary defect underlying the development of type II diabetes. In healthy conditions, insulin stimulates glucose uptake from the blood stream, but in diseased conditions the normal metabolic response is impaired. Identifying specific drug targets to restore insulin sensitivity at the cellular level and developing an effective treatment strategy require insight into both the biochemical mechanisms involved and the whole signalling network response to external cues. This study focuses on the consequences of integrating a detailed biochemical description of the insulin receptor trafficking compartment within a phenomenological model of the downstream signalling pathway. While the description of the experimental data is preserved by an iterative procedure of parameter fitting, the dynamic response of the network is highly modified, as shown by analyzing the complementary information derived from studying both connection sensitivities and node noise in the network. This is crucial considering the importance of network dynamics for identifying effective drug targets.

Original languageEnglish (US)
Title of host publicationDYCOPS 2010 - 9th International Symposium on Dynamics and Control of Process Systems, Book of Abstracts
Pages326-331
Number of pages6
EditionPART 1
DOIs
StatePublished - Dec 1 2010
Event9th International Symposium on Dynamics and Control of Process Systems, DYCOPS 2010 - Leuven, Belgium
Duration: Jul 5 2010Jul 7 2010

Publication series

NameIFAC Proceedings Volumes (IFAC-PapersOnline)
NumberPART 1
Volume9
ISSN (Print)1474-6670

Other

Other9th International Symposium on Dynamics and Control of Process Systems, DYCOPS 2010
CountryBelgium
CityLeuven
Period7/5/107/7/10

Keywords

  • Diabetes
  • Drug target
  • Insulin
  • Sensitivity analysis
  • Signalling pathway
  • Stochastic modelling

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