Mechanistic model of fuel selection in the muscle

P. de Beaudrap, G. Witten, G. Biltz, E. Perrier

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Fuel selection in human muscle is key to explaining insulin resistance. In obesity and type 2 diabetes mellitus, there is an increased content of lipid within and around muscle fibers. Changes in muscle fuel partitioning of lipid, between oxidation and storage of fat, contribute to the accumulation of intramuscular triglycerides and to the pathogenesis of both obesity and type 2 diabetes mellitus. A mathematical model of the aggregated metabolism in skeletal muscle was developed and the effects of fuel selection for lean and obese individuals under fasting conditions, insulin-stimulated conditions, and oscillating insulin conditions were examined. Model results were complementary to prior observations that elevated lipid oxidation during insulin-stimulated conditions is correlated with insulin resistance. The model also adequately simulated metabolic inflexibility between fat and glucose oxidation in the obese individual. A novel sensitivity analysis indicated the strong interaction effects of parameters of glucose and lipid oxidation pathways on the variables of each pathway.

Original languageEnglish (US)
Pages (from-to)151-163
Number of pages13
JournalJournal of Theoretical Biology
Volume242
Issue number1
DOIs
StatePublished - Sep 7 2006

Keywords

  • Fuel selection
  • Insulin-resistance
  • Model
  • Skeletal muscle

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