Effects of phenylarsine oxide on stimulation of glucose transport in rat skeletal muscle

E. J. Henriksen, J. O. Holloszy

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

The trivalent arsenical phenylarsine oxide (PAO) inhibits insulin-stimulated glucose transport in adipocytes and skeletal muscle through direct interactions with vicinal sulfhydryls. In muscle, glucose transport is also activated by contractile activity and hypoxia. It was therefore the purpose of the present study to investigate whether vicinal sulfhydryls are involved in the stimulation of glucose transport activity in the isolated rat epitrochlearis muscle by hypoxia or contractions. PAO (> 5 μM) caused a twofold increase in rate of transport of the nonmetabolizable glucose analogue 3-O-methylglucose (3-MG) that was completely prevented by cytochalasin B, the vicinal dithiol dimercaptopropanol, dantrolene, or 9-aminoacridine, both inhibitors of sarcoplasmic reticulum Ca2+ release, or omission of extracellular Ca2+. Although PAO treatment (≥ 20 μM) prevented ~ 80% of the increase in 3-MG transport caused by insulin, it resulted in only a ~ 50% inhibition of the stimulation of 3-MG transport by either hypoxia or contractile activity. PAO treatment (40 μM) of muscles already maximally stimulated by insulin, contractile activity, or hypoxia did not reverse the enhanced rate of 3-MG transport. These data suggest that vicinal sulfhydryls play a greater role in the activation of glucose transport by insulin than by muscle contractions or hypoxia. The finding that PAO inhibits the stimulation of glucose transport, but does not affect glucose transport after it has been stimulated, provides evidence that vicinal sulfhydryls are involved in the pathways for glucose transport activation in muscle, but not in the glucose transport mechanism itself.

Original languageEnglish (US)
Pages (from-to)C648-C653
JournalAmerican Journal of Physiology - Cell Physiology
Volume258
Issue number4 27-4
DOIs
StatePublished - 1990

Keywords

  • calcium
  • contractile activity
  • hypoxia
  • insulin
  • vanadate
  • vicinal sulfhydryls

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

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