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

BMC Systems Biology

Marta Cascante⁴  Philippe Rouet¹  Antonio Zorzano²  Yves Durocher³  Annie Turkieh¹  Fatima Smih¹  Romain Harmancey¹  Josep J Centelles⁴  Vitaly A Selivanov⁴  Anibal Miranda⁴  Silvia Marin⁴  Shirley Guzmán⁴ 

[1] Université Toulouse III Paul-Sabatier, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Equipe n°7, Toulouse, France;Institute for Research in Biomedicine (IRB Barcelona) and CIBER of Diabetes and Associated Metabolic Diseases (CIBERDEM), Barcelona, Spain;Animal Cell Technology Group, Biotechnology Research Institute, National Research Council Canada, Montreal, QC, Canada;Institute of Biomedicine of Universitat de Barcelona (IBUB) and CSIC-Associated Unit, Barcelona, Spain

关键词: Tracer-based metabolomics;    Bioinformatics;    Fluxomics;    Glucose metabolism;    Insulin resistance;    Resistin;   

Others  :  1126947
DOI  :  10.1186/s12918-014-0109-z

 received in 2014-05-12, accepted in 2014-08-29,  发布年份 2014

【 摘 要 】

Background

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.

【 授权许可】

   
2014 Guzmán et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 5.

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