13C metabolic flux analysis shows that resistin impairs the metabolic response to insulin in L6E9 myotubes

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DOIResolve DOI: http://doi.org/10.1186/s12918-014-0109-z
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TypeArticle
Journal titleBMC Systems Biology
ISSN1752-0509
Volume8
Issue1
Article number109
Pages112; # of pages: 12
SubjectResistin; Insulin resistance; Glucose metabolism; Fluxomics; Bioinformatics; Tracer-based metabolomics
AbstractBackground: It has been suggested that the adipokine resistin links obesity and insulin resistance, although how resistin acts on muscle metabolism is controversial. We aimed to quantitatively analyse the effects of resistin on the glucose metabolic flux profile and on insulin response in L6E9 myotubes at the metabolic level using a tracer-based metabolomic approach and our in-house developed software, Isodyn.Results: Resistin significantly increased glucose uptake and glycolysis, altering pyruvate utilisation by the cell. In the presence of resistin, insulin only slightly increased glucose uptake and glycolysis, and did not alter the flux profile around pyruvate induced by resistin. Resistin prevented the increase in gene expression in pyruvate dehydrogenase-E1 and the sharp decrease in gene expression in cytosolic phosphoenolpyruvate carboxykinase-1 induced by insulin.Conclusions: These data suggest that resistin impairs the metabolic activation of insulin. This impairment cannot be explained by the activity of a single enzyme, but instead due to reorganisation of the whole metabolic flux distribution.
Publication date
PublisherBioMed Central
LanguageEnglish
AffiliationHuman Health Therapeutics; National Research Council Canada
Peer reviewedYes
NPARC number21272845
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Record identifier5ed7c525-8610-4de2-98b8-b6fcc8e143d3
Record created2014-12-03
Record modified2016-05-09
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