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13 C metabolic Flux analysis shows that resistin impairs the metabolic response to insulin in L6E9 myotubes.
Guzmán Avilés, Shirley Doris; Marín Martínez, Silvia; Miranda, A.; Selivanov, Vitaly A.; Centelles Serra, Josep Joan; Harmancey, R.; Smih, F.; Turkieh, A.; Durocher, Y.; Zorzano Olarte, Antonio; Rouet, P.; Cascante i Serratosa, Marta
Universitat de Barcelona
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.
Diferenciació cel·lular
Metabolisme
Glucosa
Insulina
Resistència a la insulina
Cell diferentiation
Metabolism
Glucose
Insulin
Insulin resistance
cc-by (c) Guzmán Avilés, Shirley Doris et al., 2014
http://creativecommons.org/licenses/by/3.0/es
Article
info:eu-repo/semantics/publishedVersion
BioMed Central
         

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