, Volume 36, Issue 10, pp 899–906 | Cite as

Involvement of non-esterified fatty acid oxidation in glucocorticoid-induced peripheral insulin resistance in vivo in rats

  • C. Guillaume-Gentil
  • F. Assimacopoulos-Jeannet
  • B. Jeanrenaud


The mechanism by which glucocorticoids induce insulin resistance was studied in normal rats administered for 2 days with corticosterone then tested by euglycaemic hyperinsulinaemic clamps. Corticosterone administration induced a slight hyperglycaemia, hyperinsulinaemia and increased non-esterified fatty acid levels. It impaired insulin-stimulated total glucose utilization (corticosterone 15.7±0.7; controls 24.6±0.8 mg·kg−1·min−1), as well as residual hepatic glucose production (corticosterone 4.9±1.0; controls 2.0±0.7 mg·kg−1·min−1). During the clamps, insulin did not decrease the elevated non-esterified fatty acid levels in corticosterone-administered rats (corticosterone 1.38±0.15, controls 0.22±0.04 mmol/l). Corticosterone administration decreased the in vivo insulin-stimulated glucose utilization index by individual muscles by 62±6%, and the de novo glycogen synthesis by 78±2% (n=8–9 muscles). GLUT4 protein and mRNA levels were either unchanged or slightly increased by corticosterone administration. Inhibition of lipid oxidation by etomoxir prevented corticosterone-induced muscle but not hepatic insulin resistance. In conclusion, glucocorticoid-induced muscle insulin resistance is due to excessive nonesterified fatty acid oxidation, possibly via increased glucose fatty-acid cycle ultimately inhibiting glucose transport, or via decreased glycogen synthesis, or by a direct effect on glucose transporter translocation or activity or both.

Key words

Muscle glucocorticoids insulin resistance glucose transport glucose transporter glucose fatty-acid cycle lipid oxidation glycogen synthesis 


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Copyright information

© Springer-Verlag 1993

Authors and Affiliations

  • C. Guillaume-Gentil
    • 1
  • F. Assimacopoulos-Jeannet
    • 1
  • B. Jeanrenaud
    • 1
  1. 1.Laboratoires de Recherches Métaboliques Faculty and Department of MedicineUniversity of GenevaGeneva 4Switzerland

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