Indinavir alters regulators of protein anabolism and catabolism in skeletal muscle

Ly Q. Hong-Brown, Anne M. Pruznak, Robert A. Frost, Thomas C. Vary, Charles H. Lang

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

The HIV protease inhibitor indinavir adversely impairs carbohydrate and lipid metabolism, whereas its influence on protein metabolism under in vivo conditions remains unknown. The present study tested the hypothesis that indinavir also decreases basal protein synthesis and impairs the anabolic response to insulin in skeletal muscle. Indinavir was infused intravenously for 4 h into conscious rats, at which time the homeostasis model assessment of insulin resistance was increased. Indinavir decreased muscle protein synthesis by 30%, and this reduction was due to impaired translational efficiency. To identify potential mechanisms responsible for regulating mRNA translation, several eukaryotic initiation factors (eIFs) were examined. Under basal fasted conditions, there was a redistribution of eIF4E from the active eIF4E·eIF4G complex to the inactive eIF4E·4E-BP1 complex, and this change was associated with a marked decrease in the phosphorylation of 4E-BP1 in muscle. Likewise, indinavir decreased constitutive phosphorylation of eIF4G and mTOR in muscle, but not S6K1 or the ribosomal protein S6. In contrast, the ability of a maximally stimulating dose of insulin to increase the phosphorylation of PKB, 4E-BP1, S6K1, or mTOR was not altered 20 min after intravenous injection. Indinavir increased mRNA expression of the ubiquitin ligase MuRF1, but the plasma concentration of 3-methylhistidine remained unaltered. These indinavir-induced changes were associated with a marked reduction in the plasma testosterone concentration but were independent of changes in plasma levels of IGF-I, corticosterone, TNF-α, or IL-6. In conclusion, indinavir acutely impairs basal protein synthesis and translation initiation in skeletal muscle but, in contrast to muscle glucose uptake, does not impair insulin-stimulated signaling of protein synthetic pathways.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume289
Issue number3 52-3
DOIs
StatePublished - Sep 1 2005

Fingerprint

Indinavir
Skeletal Muscle
Proteins
Phosphorylation
Insulin
Muscles
Translational Peptide Chain Initiation
Ribosomal Protein S6
HIV Protease Inhibitors
Eukaryotic Initiation Factors
Muscle Proteins
Carbohydrate Metabolism
Protein Biosynthesis
Ligases
Corticosterone
Ubiquitin
Insulin-Like Growth Factor I
Lipid Metabolism
Intravenous Injections
Insulin Resistance

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

Cite this

Hong-Brown, Ly Q. ; Pruznak, Anne M. ; Frost, Robert A. ; Vary, Thomas C. ; Lang, Charles H. / Indinavir alters regulators of protein anabolism and catabolism in skeletal muscle. In: American Journal of Physiology - Endocrinology and Metabolism. 2005 ; Vol. 289, No. 3 52-3.
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Indinavir alters regulators of protein anabolism and catabolism in skeletal muscle. / Hong-Brown, Ly Q.; Pruznak, Anne M.; Frost, Robert A.; Vary, Thomas C.; Lang, Charles H.

In: American Journal of Physiology - Endocrinology and Metabolism, Vol. 289, No. 3 52-3, 01.09.2005.

Research output: Contribution to journalArticle

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