INVOLVEMENT OF NONESTERIFIED FATTY-ACID OXIDATION IN GLUCOCORTICOID-INDUCED PERIPHERAL INSULIN-RESISTANCE IN-VIVO IN RATS
INVOLVEMENT OF NONESTERIFIED FATTY-ACID OXIDATION IN GLUCOCORTICOID-INDUCED PERIPHERAL INSULIN-RESISTANCE IN-VIVO IN RATS
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DOI：
10.1007/bf02374470
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发表时间：
1993-10-01
期刊：
影响因子：
8.2
通讯作者：
JEANRENAUD, B
中科院分区：
文献类型：
--
作者：
GUILLAUMEGENTIL, C;ASSIMACOPOULOSJEANNET, F;JEANRENAUD, B
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). GLUT 4 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 non-esterified 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.
