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Modeling of metabolic insulin signaling in adipocytes
Linköping University, Department of Electrical Engineering.
2006 (English)Independent thesis Basic level (professional degree), 20 credits / 30 HE creditsStudent thesis
Abstract [en]

Active insulin receptors (IR) phosphorylate insulin receptor substrate (IRS), but it is not clear whether IRS is phosphorylated mainly by IR at the plasma membrane or by internalized IR in the cytosol. In this thesis, structural identifiability analysis and parameter sensitivity analysis is performed for models of the first steps in the metabolic insulin signaling pathway. In particular, the identifiability of the kinetic parameters governing IRS phosphorylation are investigated.

Given measurements of the relative increase in phosphorylation degree of IR and IRS, the structural identifiability analysis revealed that the parameters governing IRS phosphorylation are non-identifiable, but their ratio is identifiable. This is sufficient to study whether phosphorylation of IRS proceeds more rapidly by IR at the plasma membrane or by internalized IR in the cytosol. In the examined model structure, internalization of insulin receptors is shown to be necessary to reproduce the experimental data.

Sensitivity analysis of the parameters governing IRS phosphorylation showed that many parameters need to be known in order to obtain ``practical identifiability'' of the interesting parameters.

Place, publisher, year, edition, pages
Institutionen för systemteknik , 2006. , 52 p.
Keyword [en]
identifiability, insulin signaling, systems biology
National Category
Control Engineering
Identifiers
URN: urn:nbn:se:liu:diva-6520ISRN: LiTH-ISY-EX--06/3778--SEOAI: oai:DiVA.org:liu-6520DiVA: diva2:21850
Subject / course
Automatic Control and Communication
Uppsok
Technology
Available from: 2006-05-22 Created: 2006-05-22 Last updated: 2012-09-10

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CiteExportLink to record
Permanent link

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Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf